When given to rats, a new opioid
relieves their pain but doesn’t cause the negative side effects
typically associated with this class of analgesic, such as addiction,
respiratory depression, and constipation (Science 2017, DOI: 10.1126/science.aai8636).
“These things are big problems when we treat patients for long periods
of time with opioids,” says Christoph Stein, a professor of
anesthesiology and critical care medicine at . . .
One
hundred and eighty-seven patients with different stages of
cerebrovascular insufficiency (CI) have been examined. A diagnosis of CI
was based on the results of neurological and neuropsychological study,
ultrasonic dopplerography, rheo- and encephalography,
electrocardiography, brain MRI and eyegrounds examination. Neurological
scales were used for neurological status assessment and further data
processing. The study aimed at evaluation of tolerability and clinical
efficacy of the medication and complications in CI course. Semax treatment resulted in significant clinical improvement, stabilization of the disease progress and reduced a risk of stroke
and transitory ischemic attacks in the disease course. The drug is
featured by minor percent of side-effects and is well tolerated by
patients, including those of older age groups.
Experiments used is combination with traditional preparations (omeprasole, de-nol, and solcoseril), Semax
peptide (Met-Glu-His-Phe-Pro-Gly-Pro) possessing nootropic and
neuroprotective activity significantly promoted ulcer healing in
patients with refractory peptic ulcers. On day 14 of treatment ulcer
healing was observed in 89.5% patients receiving intranasal Semax (1% solution, 2-4 drops 3 times a day for 10 days) vs. 30.8% in the control group. Clinical studies of antiulcer activity of Semax in different combinations with usual antiulcer drugs are needed.
PMID:
12459874
What are the benefits of Semax?
Some purported benefits of Semax includes the following:
Increased memory capacity
Improved learning ability
Increased concentration, focus and perception
Increased energy and improved energy balance
Better moods
Improved immune functioning
Decrease mental strain from intellectually exhausting activities
Increase brain’s ability to adapt on chronic stress
Anxiety and depression treatment
Treatment of Attention Deficit Hyperactivity Disorder (ADHD)
Treatment for sleep disorders
Improve memory of elderly patient
Prevents symptoms of neurodegenerative disorders
TIA and stroke treatment
Optic nerve disorder treatment
Peptic ulcer disease (PUD) treatment
Protects the brain from damage
Is Semax safe to use?
Despite its strength, Semax is relatively safe for human use. There
are no serious side effects associated with it. Accounts from users who
took more than what was recommended revealed minimal side effects (e.g.
headaches). It also has a low toxicity profile and has no risk for
causing dependence or tolerance at that. Nonetheless, it is still
critical to follow the recommended dosage range.
How should you take Semax?
Please note that Semax can only be administered via the subcutaneous
administration and intranasal route. Semax should never be taken orally,
sublingually or any route other than subcutaneously as
it will be rendered inactive. The recommended daily dosage for Semax is
0.25 to 1 mg daily. For lyophilized Semax, remember to reconstitute it
with Normal Saline NaCl 0.09% before injection.
Always clean to sterile technique where possible
Intranasal administration for cognitive enhancement has been a debated consideration for many years.
Trackable results have , shall we say, varied considerably.should be limited
to 2 to 3 drops on each nostril with 0.1% Semax solution taken twice a
day. This will amount to exactly 50 mcg of active ingredient per Semax
nasal spray. Due to its long half-life (about 12 to 24 hours), you may
opt to limit Semax administration to once a day. It is also recommended
that you cycle it every 14 days to achieve its maximal effects. Please
note that the 1% Semax solution is meant for patients with severe
medical problems including stroke. Semax should not be used continuously
Funny how one thing leads to another. A few years ago BoingBoing had a link to an MIT study linking fun products like Monsanto's failed weed killing chemistry to human systems problems. The scientists who worked on that report published in Entopy april 2014 took a lot of flack from big chemo. Funny if they were so wrong you would think that a fearless monolithic behemoth like our friendly Monsanto would just reach out and find a middle ground to 'straighten the matter out" That didn't happen. The premise of the report was simple , certain widely used chemicals affect humans indirectly by attacking the healthy bacteria normally thriving in the human gut. They do that slowly over a long period of time We know that antibiotic use and abuse certainly does kill the good with the bad. The best that big Pharma does is to try to sell it's victims a processed version of the basic spectrum of gut bacteria needed to be generally healthy, Why not just give everyone 10 Kefir grains Oh, that would solve the problem, but decrease profitability. They missed rule number one Don't piss off scientists , they just work harder. Check his out and decide for your self
Inovations in the Microbiome
Revelations about microbes in the gut are shaking the foundations of medicine and nutrition
In
his lab at Rice University synthetic biologist Jeff Tabor is creating a
kind of Lilliputian naval academy. The midshipmen are so small they
can’t be seen with the naked eye. But they’re part of a vital mission to
protect U.S. naval forces from internal enemies, ranging from metabolic
disorders to anxiety and depression.
In 2014 Tabor received a three-year grant from the U.S. Office of
Naval Research (ONR) to genetically modify a harmless species of Escherichia coli
bacteria normally found in the human gut. The goal is to create an
edible probiotic organism that can hone in on developing disease and
stave it off, even before symptoms take hold. He has recently succeeded
in engineering E. coli with sensors that can detect the presence of chemicals signaling disease—at least in the mouse gut.
His ultimate aim is to design “a precision gut bacterium that
manipulates the intestinal environment in humans to keep it healthy,” he
says. This involves rewiring the genes of E. coli to transform
the cells into predictable and reliable microbial medics loaded with
engineered genetic circuits that can sense specific chemical
disturbances and fire off a battery of molecules to neutralize them.
The cells would live only a short time in the gut, perhaps six hours or
so, “just long enough to do their job,” Tabor says. Then they would die
naturally or self-destruct.
Tabor’s initial target: obesity and related metabolic issues. “We want to use a genetically engineered E. coli
cell to sense the chemicals that signal gut disturbances linked with
obesity,” Tabor says, “and then deliver beneficial molecules to prevent
weight gain.” Tabor’s work represents the fruitful collision of two hot fields:
synthetic biology, the engineering of microorganisms to make useful
products; and microbiomics, the study of the microbes living on and
inside humans and other animals, collectively known as the microbiome.
"There's great potential in this area because there are so many
widespread chronic diseases associated with the gut," says Pamela Silver
of the Wyss Institute for Biologically Inspired Engineering at Harvard
University, which published report of the first synthetic engineered gut
microbe in 2014.
The 100 trillion bacterial cells that reside in our guts play a major
role in nearly every aspect of human biology—digesting food, guiding
the immune system, even dictating mental health by sending signals to
the brain that affect mood, cognition and behavior. It’s not surprising,
then, that disruption of these gut microbial communities can lead to
disease, including obesity and related problems.
Tabor’s project is part of a larger program on the microbiome funded
by the ONR to help U.S. naval forces be more robust in the face of
stressors—changes in diet or environment, fearful situations, sleep loss
or disrupted circadian rhythms from shifting time zones or living in a
submarine. “We’re interested in how gut microbiota respond to these
stresses,” says Linda Chrisey, program officer in the ONR’s Warfighter
Protection and Application Division. “Are they contributing to the
host’s response? If so, can we tweak the microbiota to insulate the host
from the stress?”
Tabor chose to focus on obesity “because we already know a lot about
it at the molecular level,” he says, “so it’s a good model to test the
concept.” Our microbiota act like a kind of metabolic ‘organ,’ that
affects calorie and nutrient absorption, manages energy balance and
controls body weight. (Scientists aren't sure what shapes microbiomic
composition. Increasing evidence suggests that it’s determined before
birth and has to do with genetics, maternal diet and mode of delivery.)
It’s clear that some bacteria make molecules that disrupt the balance
within, causing obesity and other disorders. Studies have shown that the
gut bacteria of healthy people churn out compounds that strengthen the
intestinal wall but those of obese people make compounds that weaken the
wall. This allows bacterial molecules to pass into the bloodstream
where they do not belong, triggering an immune response. The resulting
chronic inflammation is correlated with a laundry list of ailments, from
inflammatory bowel disease to mental health disorders, such as anxiety
and depression. It’s still early in the game, but Tabor has already isolated several sensors, reengineered them and put them into a single E. coli
bacterium. He has fed the modified cells to mice and shown that the
sensors have been activated inside the mouse gut, suggesting they have
detected the target chemicals.
Tabor plans to have a single E. coli bacterium carry up to a
dozen sensors so it can detect multiple signals at one time for a more
accurate diagnosis. Ultimately, he plans to engineer these cells to
produce drugs when and where they’re called for—highly targeted
antibiotics designed to bind with and deactivate those bacterial
chemicals that might otherwise leak into the blood from the
intestine—thereby preventing the changes that lead to obesity,
inflammation and associated ills. Delivering these drugs to the exact
tissue in the body where they’re needed and nowhere else would both
decrease side effects and increase efficacy. However, "these are genetically engineered organisms, so there will
be a long debate about them," Silver says. "We'll have to weigh the
risks versus the potential benefits. But we're working to develop ways
to make these organisms inherently safe. And I think the concern over
risks will be neutralized by the benefits, especially for people who
suffer from chronic disease.”
So far, Tabor has altered only mouse microbiota. But, he says, “it’s
hard to imagine a future where we aren’t diagnosing and treating,
possibly curing, many diseases in humans by manipulating gut bacteria in
this way—diabetes, autoimmune disorders, cancer, neurological
disorders,” and, yes, weight issues.
In fact, the Navy may find creative ways to deploy these synthetic
probiotics not just to avoid obesity and its attendant problems but to
quickly shift body weight and metabolism as necessary, Tabor suggests.
“Imagine you have a team of marines going from a temperate environment,
say, at sea level, to a really cold environment, like up on top of a
mountain, in a short period of time. You want them to be able to put on
some fat quickly to be more robust in the cold environment.”
The solution? A dose of yogurt laced with synthetic probiotics that
change warfighters’ metabolism to increase fat for a couple of weeks—and
after that another dose to take it off when they return to sea level.
Maybe they will find that the mindset of "We must always be ready for /or at war is in fact an unhealthy way to live"
Doing crossword puzzles is one of many things that can help keep the brain agile. (Pixabay)
Is mental decline an inevitable part of aging? Our brains do shrink
as we get older, but new research shows it does not have to have to go
hand-in-hand with a decrease in cognitive ability. In fact, it’s
possible to enhance existing brain pathways and even create new ones as
we age. New concepts like neuroplasticity demonstrate that changes in
behavior, environment, thinking, and emotions and health can all affect
the way our brains change.
Psychiatrist Henry Emmons and psychologist David Alter have studied
how aging affects the brain and have come up with nine components to
keep the brain agile (read them below).
Some are expected: sleep more, eat well, exercise. But others are less
predictable, for example, the importance of optimism, flexibility,
empathy, connectedness and authenticity – all of which, they say, can be
cultivated at any age.
You Can Create a Younger Brain
and a Wiser Mind at Any Age
The Myth of Aging
Most of us can’t pinpoint the exact moment we began to feel older. You know, old older. It creeps up on us, an accumulation of little details and changes,
until one day we look around and find ourselves asking, almost daily: Where did I put my keys again? What’s the name of that restaurant I like? When did these stairs get so steep, anyway? It’s called a . . . wait, I know this . . . it’s on the tip of my tongue . . .hang on . . . I’ve almost remembered it . . .
The aches and pains we might expect. But the mental lapses can be
particularly unsettling. Our imaginations go to the worst possible
place—Am I losing my mind?—and that worry can be a constant fear for those of us in midlife (and those of us who are fast approaching it).
It is easy to understand why many see aging as a bad, even frightful
thing. How often have you heard someone say something like “Getting old
is not for the faint of heart”? We fear the physical pain and debility
that we so often witness, and even more so the loss of memory and mental
abilities, a loss we sometimes expect as inevitable with aging.
There is a widespread notion that the brain in particular
deteriorates as we age.
Conventional wisdom about aging used to be some
version of this: You are born with about 100 billion neurons. The brain’s development
is pretty well finished by the end of childhood. Each year after the
ages of six through twelve, more and more of your brain cells die off,
never to be seen again. The best you can hope for is to slow down this
loss of function and try to buffer the inevitable decline of aging.
Listen when we tell you: it doesn’t have to be this way!
These fearful losses of function are not a
given. Today we understand the brain in a much deeper way than ever
before, and we now know how to change the brain in positive ways. For
example, while it may be true that there is a loss of neurons as we get
older, we now also know that the brain has stem cells that can replace
some of those lost cells. In fact, the brain is remarkably resilient at
repairing itself—even after something as damaging as a stroke!
Neuroscience is teaching us some of the ways we can support that
resilience, and we will share those findings with you throughout this
book.
Yet there is more than just the hope of slowing our decline. There
are ways in which aging is actually full of possibility, because our
brains are always able to learn and our minds are continually
capable of gaining wisdom. Those abilities can enhance our lives, even
as we lose a few neurons along the way.
It is our premise that aging itself is neither good nor bad. We all
encounter aging no matter what we do, so long as we are fortunate to
live long enough. The question is not will we age, but how will we
engage the aging process? In Staying Sharp, you’ll learn
techniques for facing the challenges of the second half of life with
excitement instead of dread. You’ll discover tools for maintaining a
healthier brain, skills for enhancing wisdom, and practices that will
help you live every day with a more joyful heart. Read on!
Can I Really Feel Better at This Point in My Life?
Helen’s story is like so many others we hear in our practice. Now
that she was in her late fifties, her brain didn’t seem as sharp as it
used to. She described herself as mentally “fuzzy,” having trouble
remembering things that she used to recall quickly and effortlessly. Her
mood had been affected too, so that she was more easily frustrated and
quicker to anger. A growing list of physical ailments, though none were
serious, had eroded her naturally high levels of energy and optimism,
leaving her feeling exhausted and depleted. “I am more than
this.” Yet having tried the conventional medical routes to no avail,
she’d begun to wonder, “Will I ever improve, or is this just what I have
to accept as an inevitable part of aging?”
While you cannot stop yourself from aging, the good news is that the
kind of decline that Helen described is neither normal nor inevitable,
and you can have a lot of influence on the quality of your own aging
process.
Helen found that by practicing just a few of the exercises that
you’ll learn about in this book, she began to emerge from the mental
torpor she’d found herself in. After several weeks, she felt sharper,
the mental fog had lifted, and she was able to regain a sense of control
and contentment in her life.
It happened to Helen, and it can happen to
you too.
This clarity emerges when we learn how to align ourselves with the
natural way the brain is designed to work. The brain will simply express
what it is in the habit of expressing. When the mind is focused with
positive intentions and grows through life-affirming practices, the
positive aspects of the mind that are lying dormant can evolve into new
and joyful habits.
Becoming more vitally alive, feeling sharper and more mentally focused, and even awakening joy, is easier than you think. An East-Meets-West Approach
So how can you optimize your brain to maintain (or even further
develop) your mental acuity? You can combine cutting-edge advances in
neuroscience with ageless healing practices that have been keeping
humans healthy for millennia. And that’s where our unique backgrounds
come into play.
I am Henry Emmons, MD, and I practice as an integrative (holistic)
psychiatrist. As I neared the end of my medical training nearly thirty
years ago, I chose to become a psychiatrist because it seemed like the
natural path to understanding and embracing the whole person—body, mind,
heart, and soul. But while I was leaning toward wholeness, the field of
psychiatry was becoming more and more reductionist, often focused on
the brain (and a few brain chemicals) to the exclusion of heart, soul,
or even the rest of the body! Early in my career, I realized that
practicing psychiatry in this way wasn’t good for my patients or me. I
had to find another way.
I was always more interested in health than disease, so I refocused
my attention on what makes people healthier and happier, including the
daily choices we make to care for our bodies; how we relate to our minds
and their myriad thoughts and emotions; and the degree to which our
hearts are alive and able to embrace all that life offers, both good and
bad. This led me to study, in earnest, the fields of integrative
nutrition, lifestyle medicine, ayurvedic medicine, and mindfulness
practice. Neuroscience has been a natural way to tie all these
disciplines together.
Over the last fifteen years, with Partners in Resilience, I have
worked to weave together these disparate fields into coherent programs
to help people recover from all-too-common mental health problems,
without relying upon medication. My earlier books, The Chemistry of Joy and The Chemistry of Calm,
describe in detail these programs for depression and anxiety,
respectively. Blending Western science with Eastern wisdom, they help
take the mystery out of good mental health and offer clear road maps
that go beyond mere recovery from illness toward a more vital and joyful
life. With Staying Sharp, we aim to do the same with
aging—honor all aspects of what it means to be human, while blending the
emerging field of neuroscience with the tried-and-true practice of
mindfulness. We wish to help you not just to get by with more intact
neurons but to actually grow happier and wiser as you also grow older.
And I am David Alter, PhD. I have been involved in the practice of
neuropsychology and health psychology for nearly thirty years. Fifteen
years ago I cofounded Partners in Healing, the holistic health center
where I have explored how the brain and the mind impact health and daily
functioning. I’ve long recognized that whole health cannot be created
by a person’s psychology alone. We are all mind and body, and
my work has involved finding methods by which people can most
effectively bring together these two aspects of being human to support
whole health. That is why I have worked to help people develop their
inner capacity to heal and grow, to use their minds to rewire their
brains. My main professional goal remains assisting people to discover
the paths by which their lives can become richer, more meaningful, and
more purpose-driven. My interest in translating brain science into a therapy of practical,
teachable steps is a natural extension of my personal life. My mother
was a teacher, my father a neurologist. From early on, the interaction
between learning and brain functioning in shaping people’s lives was
modeled for me on a daily basis. Those interests led me to design
treatment programs that combine brain-based Western learning with
practical skill development drawn from Eastern healing traditions for a
wide range of conditions—migraine, chronic pain, and digestive
disorders, to name a few.
While brain science has certainly shaped my personal outlook and
practice, an even more powerful influence for this book has been the
spiritual tradition in which I was raised. In a word, it taught me hope.
As Elie Wiesel, a Nobel Prize–winning author, has said, “Hope is like
peace. It is not a gift from God. It is a gift only we can give to one
another.” My personal hope is that this book is our gift to you and that
through your reading and applying of the information and practices we
present, you will find renewed hope about the reward and fulfillment
that awaits you in the second half of your life.
We have worked together as a medical doctor and a neuropsychologist
for more than twenty-five years, integrating the best of Western
medicine with complementary mind-body healing practices. We share a deep
commitment to helping people discover the powerful and often underused
resources they have within themselves, skills that with practice can
enable you to live a more resilient and joyful life. In Staying Sharp we share with you these ideas and practices that we have been developing throughout our professional lives.
Our work is deeply rooted in the foundational advances in
neuroscience of the last fifteen years. We now have a much more complete
picture of what the brain does and how it works. For example, you may
have heard of neuroplasticity, the brain’s ability to rewire in
the face of new experience. This means that we are designed to change
and adapt throughout life—we never stop learning! New experience prompts
our brains to adjust and adapt, to create new pathways, and we can
influence the quality of and direction that those pathways take. By the
choices you make, the experiences you seek, and the skills you cultivate
through repeated practice, you are already literally rewiring your
brain. We aim to show you how to use those choices, experiences, and
skills to rewire your brain to create a more vibrant mind. But what’s truly fascinating is that the more we learn about the
brain, the more validation science is giving to traditional and ancient
methods of understanding how the mind works.
Mindfulness—long a
staple of Buddhist thought and practice—actually can be measured and
studied using the newest brain-imaging techniques by today’s
neuroscientists. And self-regulation skills are not just
important for children in the classroom; they are essential life skills
that predict a child’s future success and happiness as an adult. In
fact, Eastern tradition and Western science are working together (and
validating each other) in new, exciting ways every day. That
intersection is at the center of the work we do with our patients, and
it’s what we will teach you in Staying Sharp. With this book we aim to translate this science and wisdom into an
easily understood framework you can follow to maintain and even rebuild a
youthful mind, coupling these key concepts with practical and
accessible steps that anyone can take at any age.
These steps are
especially helpful for individuals like you, who are seeking to thrive in the second half of life.
When Helen began to practice what we will soon teach you, she
effectively tapped into the plasticity of her brain and the resilience
of her mind. Neuroscience has shown us that the circuits of the brain
are designed to recognize repeating patterns. And by extension, when our
mind does something repeatedly, that part of the mind gets stronger.
What we focus upon grows.
This inborn tendency toward pattern recognition can be refined into a
positive trait: for example, we can begin to notice the many ways that
our spouse, flawed though he or she may be, acts in ways that we
appreciate. And sometimes we can apply our learned patterns in new ways
when we encounter something new and unexpected—such as a random act of
kindness by a stranger that evokes a feeling of gratitude within
us—because we may be able to draw from some past experience with a
similar pattern.
But the repeating of old patterns works against us, as it did for
Helen, when life becomes a series of unending repetitions—“more of the
same.” This familiarity can lead to feelings of malaise or even mental
dullness, and since so many of these patterns operate automatically and
outside of our direct awareness, they can easily get in the way of
personal growth.
But the story doesn’t have to end there, because we are conscious
beings, capable of growth through purpose and intention. The capacity
for changing our brains is truly staggering. It is said that the number
of possible combinations of connections among the brain’s 100 billion
neurons, each of which has up to ten thousand connections with other
neurons, is larger than the number of atoms in the known universe!
With consistent and repeated use of the practices described in this
book, Helen’s neural circuits began to change for the better. By
integrating the modest exercises and body-based meditations that follow,
Helen felt her physical body begin to come alive with sensation. She
regained a sense of being embodied—a whole person
interconnected to a body with thoughts, feelings, sensations, and wise
emotions that she could now begin to assert. She not only felt better
physically; she also felt clear-headed and more mentally nimble.
Helen’s story is far from unique. While your own story may contain
different particulars, the avenues that she pursued are just as relevant
to you. She sought connection to herself and to her life; she sought
meaning and purpose; she sought pleasure and novelty; and she sought a
basis of hope and belief that she could live a life that reflected the
best she had to offer.
Resilient Brain, Vibrant Mind, Awakened Heart
We tend to use the words brain and mind interchangeably
in our culture, but in fact they’re two very different things, and they
each need something different in order to age well and stay sharp.
Living and aging joyfully requires three core traits that we call resilience, vibrancy, andawakening.
Resiliencerefers to the brain, vibrancydeals with the mind, and awakeninginvolves the heart and enables us to connect meaningfully with others. So what is resilience? It involves the ability to keep a positive
mood and a sense of well-being even in the face of significant
adversity. Resilience is a result of a healthy, well-functioning brain—a
youthful brain. The capacity for resilience is built into our
brains: it is natural. But the ability to direct this capacity for
resilience is a function of a vital, well-integrated, radiant mind—a
vibrant mind.
We consider the brain to include the physical aspects of this
pair—the anatomical structures, the physiological functions, and the
chemical processes that keep us ticking. The brain is like an orchestra.
When it is working well, when all the musicians are well trained, well
rested, and well fed, we are resilient. When it is fully
functioning, the brain has all the elements it needs to make rich,
resonant, beautiful music. All but one, that is. You could bring
together the most talented musicians with the finest instruments, but
still they would not sound good without a conductor to help them come
together with a beautifully coherent sound. That is the function of the
mind.
The concept of mind is sometimes hard to grasp, since it is not so
concrete as anatomy or chemistry. In our view, the mind serves as a
guiding principle. It involves the mental, emotional, and social
abilities that can generate and extend the capacity for joy. Like the
conductor, it oversees the necessary attention to detail, but it doesn’t
get lost in it. Mind sees the big picture, and that includes the vast
array of human capabilities that can transform a series of discrete
notes into a symphonic work of art. Mind allows us to use our brain and
body to create a life of beauty and joy.
Beautiful music can be made by a youthful brain and a vibrant mind
working together in harmony. But is it still beautiful if there’s no one
to hear it? Doesn’t music need to connect with others in order to
fulfill its purpose? That is where an awakened heart comes in. Heart
involves the capacity that each of us has, whether we’ve used it or not,
to connect deeply with others, with ourselves, and with a life full of
meaning. It is through the heart that we can fully awaken to our lives
and reap the benefit of having a resilient, youthful brain and a vital,
vibrant mind. When the mind is conscious and the heart is awakened, we
may go well beyond resilience. We may thrive.
As in the metaphor of the orchestra, neither brain nor mind is much
good without the other. And what good would the orchestra and conductor
be without an audience to enjoy them? Each and every one of us wants and
needs these three elements of ourselves—a resilient brain, a vibrant
mind, and an awakened heart—to be as healthy and vital as possible, to
thrive for the length of our days.
In our work, we constantly encounter people like Helen who are asking some version of this essential question: How can I live more joyfully, age more gracefully, see with more clarity, and love more deeply forthe remainder of my life? We
hope that questions like this animate you as well, and we intend to
explore how you might, through nine core concepts, answer them. These
lessons, applied in simple ways, can help you build a resilient brain,
cultivate a radiant mind, and discover an awakened heart—laying the
foundations for your own joyful life.
How to Use This Book
Learning how to integrate brain, mind, and heart into a harmonious
whole has never been more needed. The sheer number of demands that
compete for our limited time, attention, and energy is unprecedented in
human history, and it is no wonder that we cannot always manage them
with ease. This pressure may partially account for the explosion of
chronic health challenges that plague people the world over. And with an
aging population, experts expect an epidemic of age-related brain
illnesses that society will be ill equipped to confront. In the face of
these challenges, developing the resilience and vitality to better adapt
and thrive in the second half of life has never been more urgent.
The second half of life will no doubt be filled with unavoidable
challenges. But there is a clear path through these challenges, a path
rooted in brain science, in practices attentive to the physical needs of
body and brain, in mindful awareness, in habits of intimacy. On this
path you will move forward, despite life’s hazards, toward joy.
This book is divided into four parts. Part 1 provides the background
that we think will help you make more sense of the chapters that follow.
Chapter 2 focuses on the structures of your brain that help you pay
attention with mindful intention, while chapter 3 show us how to put
that knowledge to use by describing how we can choose to apply our
attention to become more present and aware.
The heart of our approach is the Staying Sharp program. This program,
described in parts 2–4 of the book, consists of nine key lessons from
neuroscience that together provide the key elements to growing and
maintaining a youthful brain. Each chapter introduces one key lesson,
with the first three keys (chapters 4–6) devoted to building a resilient
brain; the next three keys (chapters 7–9) focus on cultivating a
vibrant mind; and the final three keys (chapters 10–12) focus on discovering how to awaken your heart. The Nine Keys to Staying Sharp
A youthful brain loves movement. In chapter 4, you’ll learn
how exercise and moving your body mindfully can directly improve brain
health, energy, and the quality of your emotions.
A youthful brain is well rested.Sleep problems seem to
rise exponentially as we age. In chapter 5, you’ll learn how to recharge
your mind through safe, natural, mind-body approaches to sleep.
A youthful brain is well nourished.In chapter 6, you’ll
learn about the best brain foods and supplements, as well as ways to
bring mindful approaches to your eating habits.
A youthful brain cultivates curiosity. In chapter 7, we
discuss the potent brain fertilizers of novelty, play, and wonder and
how you can incorporate more of these into your life.
A youthful brain is flexible. In chapter 8 we will learn
about neuroplasticity, the brain’s amazing capacity to change and adapt
through the whole of our lives. By enhancing your own ability to remain
flexible, you will be able to thrive despite the challenges you will
undoubtedly face in the second half of life.
A youthful brain is optimistic.While we naturally vary in
degrees of optimism, it is a skill that can be honed with great rewards.
In chapter 9, we highlight the science of optimism and show you how to
cultivate this inner quality to enhance the legacy that you would like
your life to have.
A youthful brain is empathic.Our brains are wired to care,
to be generous and compassionate, and when we grow in the capacity to
love well, so does our happiness. In chapter 10, we discuss the science
of empathy and show how you can use it to grow in your own level of joy.
A youthful brain is well connected. We are social beings,
and our brains change when we are around others. In chapter 11, we
contemplate the importance of connecting with others in meaningful ways
and developing an ever growing sense of belonging in the world.
A youthful brain is authentic. Chapter 12 points us toward
one of the most important goals of a well-lived life: to become more and
more fully yourself. Living authentically is the fruit of all the other
practices, and it can also be its own pursuit when we develop the
capacity to live consciously and fully, expressing our own deepest
nature.
The
peptide semax affects the expression of genes related to the immune and
vascular systems in rat brain focal ischemia: genome-wide
transcriptional analysis
The
nootropic neuroprotective peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro)
has proved efficient in the therapy of brain stroke; however, the
molecular mechanisms underlying its action remain obscure. Our
genome-wide study was designed to investigate the response of the
transcriptome of ischemized rat brain cortex tissues to the action of
Semax in vivo.
Results
The
gene-expression alteration caused by the action of the peptide Semax
was compared with the gene expression of the “ischemia” group animals at
3 and 24 h after permanent middle cerebral artery occlusion (pMCAO).
The peptide predominantly enhanced the expression of genes related to
the immune system. Three hours after pMCAO, Semax influenced the
expression of some genes that affect the activity of immune cells, and,
24 h after pMCAO, the action of Semax on the immune response increased
considerably. The genes implicated in this response represented over 50%
of the total number of genes that exhibited Semax-induced altered
expression. Among the immune-response genes, the expression of which was
modulated by Semax, genes that encode immunoglobulins and chemokines
formed the most notable groups.
In
response to Semax administration, 24 genes related to the vascular
system exhibited altered expression 3 h after pMCAO, whereas 12 genes
were changed 24 h after pMCAO. These genes are associated with such
processes as the development and migration of endothelial tissue, the
migration of smooth muscle cells, hematopoiesis, and vasculogenesis.
Conclusions
Semax
affects several biological processes involved in the function of
various systems. The immune response is the process most markedly
affected by the drug. Semax altered the expression of genes that
modulate the amount and mobility of immune cells and enhanced the
expression of genes that encode chemokines and immunoglobulins. In
conditions of rat brain focal ischemia, Semax influenced the expression
of genes that promote the formation and functioning of the vascular
system.
The immunomodulating effect of
the peptide discovered in our research and its impact on the vascular
system during ischemia are likely to be the key mechanisms underlying
the neuroprotective effects of the peptide.
Ischemic
brain stroke is one of the major contributors to mortality and
disability worldwide. As the result of a critical reduction of blood
flow in the brain, it causes massive loss of neurons and leads to the
formation of the necrotic core and the penumbra zone [1].
One
of the drugs that is effectively employed currently in cerebral stroke
therapy is the Semax (Met-Glu-His-Phe-Pro-Gly-Pro), which is a synthetic
peptide consisting of a fragment of ACTH(4–7) and the C-terminal
tripeptide Pro-Gly-Pro (PGP). Studies have shown that Semax promotes the
survival of neurons during hypoxia [2] and glutamate neurotoxicity [3].
It also shows neuroprotective properties and contributes to
mitochondrial stability under stress induced by the deregulation of
calcium ion flow [3]. The action of Semax causes the inhibition of nitric oxide synthesis [4], improves the trophic supply of the brain [5], and protects the nervous system effectively against diseases of the optic nerve [6]. This peptide also possesses nootropic activity [7].
However,
the molecular mechanisms underlying the action of Semax remain unclear.
We have previously shown the effect of Semax on the expression of genes
that encode neurotrophic factors and their receptors in an experimental
model ischemia in the rat brain [8,9].
This
genome-wide study was performed to elucidate the transcriptome response
of the ischemized focal tissues of the rat brain to the action of Semax
in vivo. The main task of our study was to identify genes with an
altered expression that accounts for the positive effect exerted by
Semax in the treatment of patients with ischemic stroke [10,11].
Semax-induced increase and decrease in gene expression
The
genome-wide expression changes induced by Semax in rat brain cortex
tissues damaged by focal ischemia were studied using the genome-wide
RatRef-12 Expression BeadChip (Illumina, USA), which contains 22,226
genes, according to NCBI. Data on the gene expression changes induced by
the peptide were compared with the gene expression levels in the
“ischemia” group at 3 and 24 h after pMCAO.
The largest
number of genes (96) that exhibited altered expression (cut-off 1.50)
in response to Semax administration was detected 3 h after the onset of
ischemia (Additional file 1);
moreover, the amount of the genes with decreased expression was
insignificantly larger than that of those with increased expression
(Figure 1). Semax altered the expression of 68 genes 24 h after occlusion (Additional file 2):
the expression of 51 genes was increased and the amount of genes with
decreased expression was considerably lower than that observed at 3 h
after the onset of ischemia.
Genes that were up- and downregulated.
The x-axis shows the condition of the experiment and time after pMCAO.
The y-axis represents the number of genes that exhibited changed
expression in these conditions. The cut-off of gene-expression changes
was 1.50. ...
Note
that different gene groups exhibited Semax-induced alteration of
expression at 3 h and 24 h. The overlapping group comprised only 10
genes with responses to the peptide that were contradictory (Table 1).
Comparison of genes that exhibited Semax-induced alteration of expression levels after pMCAO
Molecular functions of the protein products of genes with altered expression under Semax treatment
The
grouping of the genes according to the molecular functions of their
products and to the iReport Web tool revealed that the expression of
transcription regulator genes was predominantly enhanced, and that that
of genes encoding transmembrane receptors, transport proteins, and
various enzymes was decreased 3 h after the onset of ischemia under
Semax treatment (Figure 2A);
about 39% of the genes with altered expression encoded proteins with
molecular functions that were unrelated to the groups presented or were
not yet identified. Gene expression was increased mostly at 24 h
(Figure 2B). The largest increase in expression was observed for immunoglobulin and cytokine (chiefly chemokine) genes (Table 2). The molecular functions of 24% of the protein products of the genes that exhibited altered expression levels were unknown.
Molecular functions associated with the up- and downregulated genes.
The x-axis shows the categories of molecular functions. The y-axis
represents the number of genes associated with selected cellular
functions. The genes that were upregulated are indicated ...
Genes related to the immune system and exhibited Semax-induced alteration of expression levels
Biological
processes that were significantly associated with the genes that
exhibited altered expression levels in response to the administration of
the peptide
We used an online program [12]
to analyze genes with altered expression in response to the
intermittent administration of Semax to ischemized animals. This led to
the identification of several biological processes that were associated
with the gene expression changes observed (Figure 3). The reliability of these processes was calculated by Fisher’s exact test.
Biological processes based on the genes that exhibited alteration in their expression levels under Semax treatment. The x-axis is the absolute value of the log transformed P-value, which means that a smaller P-value has a larger positive value on the ...
Three
hours after pMCAO, Semax exerted considerable influence on various
general biological processes (proliferation, differentiation, and
migration of cells), on vascular system processes, brain cell processes,
and on the immune system (Figure 3A).
Twenty-four hours after occlusion, similar to observed effects 3 h
after the procedure, Semax, acting in conditions of focal ischemia,
altered the expression of genes involved in cell proliferation and
migration. One day after the occlusion, however, unlike at 3 h after the
procedure, additional processes supplemented the general processes,
namely, the organization of the cytoskeleton, tissue development, and
the quantity of metal (Figure 3B).
Special attention should be drawn to the processes that were most
significantly associated with immune cell activity and calcium ion
regulation, namely, the migration and attraction of dendritic cells
(DCs), the attraction of leukocytes (Figure 3B), and the regulation of the levels of Ca2+ (Figure 3B, Table 3).
Genes related to the quantity of Ca2+ and exhibited Semax-induced alteration of expression levels (24 h)
Semax altered the expression of genes related to the immune system to a large degree (Table 2).
In conditions of experimental focal ischemia, the action of Semax
observed 3 h after the onset of ischemia influenced the expression of
several genes that are involved in the regulation of the activity of
immune cells: macrophages, neutrophils, and lymphocytes (Figure 3A).
The effect of Semax on the immune response was increased significantly
24 h after pMCAO. The genes involved in this process represented over
50% of the total amount of the genes that exhibited altered expression
levels. Semax-induced upregulation of transcripts was observed for a
majority of the immune-response genes; among these, immunoglobulin genes
formed the most prominent group, with half of them exhibiting the
highest amplitude of expression alteration among the genes for which the
level of transcripts was affected by the peptide (Table 2).
Another
remarkable group of genes with Semax-induced alteration in expression
levels consisted of genes involved in the vascular system. The
expression of 24 and 12 genes was altered 3 and 24 hours after pMCAO,
respectively (Table 4).
Genes related to the vascular system and exhibited Semax-induced alteration of expression levels
Genes that regulate the levels of Ca2+ formed a separate group of genes exhibiting a significant Semax-induced alteration of expression 24 h after occlusion (Table 3).
Different profiles of gene expression elicited by Semax administration 3 and 24 h after pMCAO
The
dynamic state of mRNA expression in mammalian tissues changes during
pathophysiological processes and after the introduction of medicinal
peptides into the organism. In this context, we studied transcriptome
changes caused by the action of neuropeptide Semax in the ischemized rat
brain cortex. This genome-wide study showed that Semax affected the
transcript level of several dozens of genes 3 and 24 h after pMCAO;
however, the functional significance of many of them remains unknown.
Three
hours after pMCAO was used in the analysis as a time point inside the
therapeutic window of the drug and within the response time of
early-response genes [13].
At that time point, we found a considerable alteration of the
expression of genes encoding transcription factors that could set off
new signal pathways that allow the correction of the destructive
processes that developed after vascular occlusion. During the active
stage of ischemia and the response of late-response genes, i.e., 24 h
after pMCAO, we observed increased levels of transcripts encoding
transmembrane receptors and enzymes, especially cytokines and
immunoglobulins. One can presume that processes initiated by
transcription factors during the first hours of therapy of ischemized
animals were developing further. Several similar processes were observed
in the course of the associative analysis of biological processes.
Response
of immune system cells to Semax administration and regulation of the
expression of genes encoding chemokines and immunoglobulins
The
detailed analysis of genes that exhibited altered levels of expression 3
and 24 h after pMCAO allowed the determination of the effect of Semax
on various biological processes that were categorized under broad
subgroups, namely, general category, brain cell, immune, and vascular
processes. The neuroprotective and nootropic properties of Semax were
previously associated only with events that are directly relevant to
nervous tissues [2,7,11].
Here, we uncovered the action of Semax on the immune system for the
first time. Three hours after pMCAO, Semax acted on microglia and immune
system cells. The process of leukocyte activation was affected most
significantly (P-value = 7.6 × 10−8) in the immune response
subgroup. The processes that developed 24 h after pMCAO, which involved
leukocytes, remained significant. In addition, Semax affected DCs, the
presence of which in rat cerebral hemisphere ischemia-damaged tissues
had been reported by other researchers [14]. DCs constitute a heterogeneous class of antigen-presenting cells that are capable of immune response initiation [15] and cytokine production [16].
Both
inflammation and immune response play an important role in ischemic
stroke. It is well known that the penetration of inflammatory/immune
cells into brain tissues during the postischemia hours aggravates the
situation [17-19].
In addition, no data have been reported to date indicating the presence
of a specific cause-and-effect relationship between the penetration of
leukocytes into the damaged tissues and the pathogenesis of the ischemia
itself [20]. However, some studies support the neuroprotective abilities of immune cells [21,22].
It
should be mentioned that the most noticeable immune response to Semax
action was observed at 24 h after pMCAO. A high level of immunoglobulin
transcripts was found at that time point in the ischemized rat brain
cortex. Several studies had shown previously that intravenous
immunoglobulin (IVIG) has a strong neuroprotective effect against
ischemic impairment of the brain [23]. It is believed that IVIG application is one of the options for acute brain stroke therapy [24].
Whether or not the neuroprotective effect of Semax can be a consequence
of the enhancement of the expression of immunoglobulin should be
addressed in future studies.
Cytokines (particularly
chemokines), which are one of the most important participants in the
immune response, were also expressed actively 24 h after pMCAO under the
influence of Semax in the region of the brain where the ischemic lesion
was localized. Many reports have described chemokine expression in
astrocytes, microglia, and even neurons [25]. It is accepted that some chemokines and their receptors are involved in various neurodegenerative diseases [26], including ischemic brain damage [27].
Recent
research has shown that chemokines are a unique class of neuromediators
that ensure the cross-talk between neurons and cells from their
surrounding microenvironment [28].
In accordance with this, the division of chemokines into pro- and
anti-inflammatory factors seems to be too simplified and gives rise to
contradicting opinions regarding the neuroprotective and
neurodegenerative functions of chemokines [29].
Enhanced expression of chemokine-encoding genes is one more evidence in
favor of the possible existence of a Semax immunomodulatory effect in
conditions of focal cerebral ischemia of the brain.
Semax-induced
activation of chemokine genes presumably accounted for the altered
transcript level of genes associated with the regulation of the quantity
of Ca2+ (Figure 3B, Table 3). The ability of some chemokines to raise the level of intracellular Ca2+, which plays a messenger role in nervous tissues, has been described in several studies [30,31]. A study that used human neutrophils [32] offered experiment-based support of the effect of Semax on the Ca2+ level in cells, and showed an increase in Ca2+ levels caused by the effect of Semax on the mechanisms that regulate Ca2+-dependent channels.
It
is well known that ischemia-induced energy depletion in cells results
in disturbed operation of potential-dependent calcium channels and Na+/Ca2+ pumps, excessive intracellular accumulation of Ca2+ ions, and neuronal death [33].
However, it has been shown that Semax contributes to neuron
survivability in the conditions of glutamate neurotoxicity that
accompany ischemia [3]. Some authors have suggested that cellular death is caused by the Ca2+ influx pathway, and not by Ca2+ load [34]. Possibly, the neuroprotective effect of Semax on ischemia-damaged nervous tissues includes the impact of Ca2+ penetration into the cell on the regulatory processes. This idea is based on recent studies of the neuroprotective effect of Ca2+-activated potassium channels in conditions of brain ischemic damage [35,36].
The
opinions on the role of the immune system in the pathogenesis of
ischemia vary. Studies are available regarding the contribution of the
immune system to ischemic damages [37], the neuroprotective and healing effect of immune-cell activation [38,39], the protective role of the immune system, and its therapeutic function [40-42].
It cannot be ruled out that the observed effect of Semax on brain
stroke can be explained by its impact on protective immune mechanisms.
Some recent reports have described interactions between nervous tissues
and the immune system, which were observed after the administration of
neuropeptides. For instance, the nootropic medication cerebrolysin
favored the survival of immunocompetent cells [43]. Another preparation, the vasoactive intestinal peptide (VIP), which has neurotrophic effects, acted as an immunomodulator [44].
The possible effect of neuromodulation on the consequences of ischemia
is believed to be real, although it has not been studied sufficiently [45].
Response of the vascular system to the administration of the neuropeptide Semax
Here,
we found changes in the expression levels of several genes involved in
the functioning of the vascular system as a response to Semax
administration. The formation of new blood vessels in the ischemized
areas represents one of the approaches used in the treatment of brain
stroke [46].
It should be mentioned that the presence of immune cells in the damaged
tissues is a typical feature of postischemic revascularization [47].
Three hours after pMCAO, Semax affected the expression of genes
involved in vasculogenesis and the transcription levels of genes
associated with hematopoiesis and the migration of endothelial cells.
Some signal pathways are well known to be active in both hematopoiesis
and vasculogenesis [48].
Moreover, a large number of genes are expressed in both endothelial
cells and hematopoietic precursor cells of the adult organism [49,50].
Three hours after occlusion, Semax altered the expression of genes
associated with the artery vasodilation process as well. Our earlier
studies showed that capillary bore extension was observed as early as
15 min after the administration of the peptide [9].
As shown in Figure 3B,
24 h after occlusion, Semax affected the development of the endothelial
tissue and the migration of smooth muscle cells, which was an
indication of vessel formation and stabilization [48].
Finally, another biological process, i.e., the activation of blood
cells, was affected by Semax 24 h after pMCAO, which followed logically
after the process of the formation of blood cells induced by Semax 3 h
after the occlusion.
Thus, as
demonstrated here, the action of Semax on the expression of genes that
ensure the formation and functioning of the vascular system in ischemic
conditions also uncovered its possible vascular and regenerative
properties, in addition to its neuroprotective and vasoactive effects.
In
this study, we analyzed the action of the neuroprotective peptide Semax
on the transcriptome of rat brain cortical cells in conditions of
experimental focal ischemia. Although Semax has been shown to be
effective in brain stroke therapy, the molecular mechanisms underlying
its neuroprotective action remain unknown.
As shown
here, Semax influenced various biological processes that contribute to
the functioning of the different systems of the organism. The immune
response was most markedly affected by the action of Semax. The peptide
increased the amount and mobility of immune cells and enhanced the
expression of chemokine and immunoglobulin genes.
Our
data showed that Semax is likely to influence processes that accompany
the formation of new blood vessels during early ischemia cascade stages,
as well as their stabilization at later stages.
The expression of genes responsible for the intracellular level of Ca2+
was sensitive to Semax administration against the background of the
unfolding pMCAO-induced neurodegenerative processes. Our results showed
that Semax enhanced the expression of genes encoding protein products
that promote intracellular Ca2+ accumulation. Possibly, the
neuroprotective effect of Semax on ischemia-damaged nervous tissues
includes an impact on processes involved in the incorporation of Ca2+ into cells.
Thus,
the immunomodulating effects of Semax described here, as well as its
influence on the vascular system in conditions of ischemia, are likely
to be key factors in the neuroprotective effects of the peptide. It
cannot be ruled out that the large amount of genes that exhibited
changed levels of expression, the functions of which remain unknown or
not well studied, will help disclose other, hitherto unknown pathways of
Semax action on damaged brain tissues. We must state at the same time
that the baffling complexity of the multicomponent nature of cerebral
ischemia and the ability of Semax to affect a large number of biological
processes require future research to uncover the full scope of the
mechanisms of action of this peptide.
All
experimental protocol were approved by Bioethics Comission of Lomonosov
Moscow State University in accordance with the National Institutes of
Health Guide for the Care and Use of Laboratory Animals (NIH Publ. no.
80–23, revised 1996). We used adult male Wistar rats (270–320 g)
maintained on a 12 h light/dark cycle at a temperature of 22–24°C with
free access to food and water.
Focal cerebral ischemia model
We applied the model of “focal cerebral ischemia” induced as previously described [51].
The irreversible electrical coagulation of the distal segment of the
left middle cerebral artery was performed under anesthesia with chloral
hydrate (300 mg/kg).
Focal cerebral ischemia was induced by direct pMCAO, involving craniotomy technique as previously described [52]
without occlusion of carotid artery. In detail, anesthesia was induced
by intraperitoneal administration of chloral hydrate (400 mg/kg body
weight). The left middle cerebral artery (MCA) was exposed via the
transtemporal approach. A 1.5 cm scalp incision was made at the midpoint
between the right eye and the right ear. The temporalis muscle was
separated in the plane of its fiber bundles and retracted in order to
expose the zygoma and squamosal bone. Using microsurgical technques, a
burr hole, 2 mm in diameter, was made with a dental drill 1 mm rostal to
the anterior junction of the zygoma and the squamosal bone. The dura
mater was carefully pierced with a scalpel. The exposed MCA was isolated
and occluded by short coagulation using a bipolar coagulator. The
craniotomy was covered with a small piece of gelfoam, the temporalis
muscle and overlying skin were allowed to fall back and were sutured
separately. After suturing, rats were returned to their cages until
sacrifice. The operation was last about 30 min.
Experimental groups
Animals
were divided into two groups: (1) “ischemia” and (2) “ischemia + Semax”
groups. pMCAO was performed in all animals. During the experiment,
ischemia + Semax animals were given intraperitoneal injections of Semax
(100 μg/kg), whereas ischemia animals were injected with saline. The
injections of Semax or saline were performed 15 min, 1, 4 and 8 h after
pMCAO.
The rats were decapitated under anesthesia with
ethyl ether 3 and 24 h after the operation. According to data from the
literature, significant events in the formation of a stroke area, such
as excitotoxicity, mitochondrial damage, emergence of reactive oxygen
species, and apoptosis, occur within the first 3 h after occlusion of an
artery [53],
and the expression of genes at the early stage of ischemia can be
studied at this time point. At the 24 h time point the infarction area
reaches its maximal dimensions and the formation of the penumbra is
completed [54].
Each
time point included at least five animals. We isolated the
frontoparietal cortex of the ischemic animals, in which, according to
histological analysis of our earlier research, the damaged area was
localized [51]. Total RNA was isolated from tissue samples.
Microarray data analysis
Microarray
experiments were carried out at ZAO ''Genoanalytica'', Moscow, Russia.
Total RNA was isolated from tissue samples using guanidine thiocyanate [55].
RNA integrity was assessed by comparison with the rRNA bands obtained
in agarose gel electrophoresis under denaturing conditions. RNA was
quantified using NanoDrop, and its quality was assessed using an Agilent
RNA 6000 Nano Chip. Total RNA (400 ng) was amplified using an Illumina®
TotalPrep™ RNA Amplification Kit (Ambion, USA) containing 22,523 probes
for a total of 22,228 rat genes selected primarily from the NCBI
Reference Sequence database (Illumina, USA). The Illumina RatRef-12
Expression BeadChip was used in accordance with the manufacturer’s
instructions. The BeadArray Reader was employed for data acquisition,
and the analysis was accomplished with the help of the Genome Studio
software (Illumina, USA) using the gene-expression module. The
statistical algorithm used in GenomeStudio gene expression analysis is
the Illumina Custom error model.
Functional analysis
The interactive Web-based Ingenuity iReport program [12] based on Fisher’s exact test (P-value
< 0.01) was applied to identify the molecular functions of the
products of the genes that exhibited altered expression in the
conditions established, as well as signaling pathways and statistically
significant biological processes. Ingenuity iReport helps the quick
identification of especially significant genes, signaling pathways, and
processes that are most relevant to the experimental data. Only those
genes with a change in expression of at least 1.5-fold from the baseline
value and whose P-value lower 0.05 were selected for iReport analysis.
Availability of supporting data
The
data sets supporting the results of this article are available in the
ArrayExpress repository (European Bioinformatics Institute, Cambridge,
UK) [56] with series accession number E-MTAB-1864 (https://www.ebi.ac.uk/biosamples/group/SAMEG148775).
ACTH:
Adrenocorticotropic hormone; pMCAO: Permanent middle cerebral artery
occlusion; MCA: Middle cerebral artery; CNS: Central nervous system; DC:
Dendritic cells; IVIG: Intravenous immunoglobulin; VIP: Vasoactive
intestinal peptide; MHC I and II: Major histocompatibility class I and
II.
EM
- carried out the molecular genetic studies and drafted the manuscript;
NM - synthesized Semaks and participated in the design of the study; VS
- designed the focal ischemia model; OP - performed the operations of
experimental animals; VD - isolated the frontoparietal cortex of the
ischemic animals, obtained the RNA from the tissue samples; LD – have
made substantial contributions to interpretation of data and have been
involved in revising manuscript critically for content; SL - have given
final approval of the version to be published. All authors read and
approved the final manuscript.
List
of all genes that exhibited changed expression under Semax treatment
(3 h after pMCAO). All transcripts that showed significant difference
between the “ischemia + Semax” and “ischemia” animal groups 3 h after
pMCAO. In the table, P-values are in the form of an exponential number format. Entrez Gene is NCBI’s repository for gene-specific information.
List
of all genes that exhibited changed expression under Semax treatment
(24 h after pMCAO). All transcripts that showed significant difference
between the “ischemia + Semax” and “ischemia” animal groups 3 h after
pMCAO. In the table, P-values are in the form of an exponential number format. Entrez Gene is NCBI’s repository for gene-specific information.
This
study was partially supported by grants of the Russian Foundation for
Basic Research (11-04-00843, 12-04-31528, 13-04-40083-Н), and the
“Molecular and Cell Biology” Program of the Russian Academy of Sciences,
and the Federal Program for Support of Scientific Schools of the
Russian Ministry of Science and Education.
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