Semax: efficacy in experimental brain ischemia

Experimental study on Wistar rats showed that the use of Semax with global cerebral ischemia in animals has some positive effect, significantly reducing the severity of neurological deficit during the first 6.5 hours compared with those in the control group. The observed trend of increasing animal and prolongation of survival until the first death in the group may also be due to the neuroprotective properties of the drug.

In the study of the effects of Semax models of acute focal cerebral ischemia established increase animal survival after experimental stroke, a significant decrease in the frequency of bleeding complications and severity of neurological deficit.

Semax efficiency in the carotid ischemic stroke

In a clinical trial of Semax in acute focal cerebral ischemia in humans criteria for inclusion in the study were patients with a clinical diagnosis of the first in the life of ischemic stroke in the carotid system, age 45-75 years, a clear mind or moderately expressed disorder of consciousness to the level of sopor, initiation of therapy within 12 h of onset. We were excluded patients with recurrent stroke, and residual effects of stroke, other neurological diseases or severe somatic pathology in the stage of decompensation, as well as in patients with acute myocardial infarction (within the last 6 weeks), atrioventricular block degree II-III.

Patients were randomly and blindly assigned to placebo were intranasally or semax in one of three doses - 6; 12 and 18 mg / day for 5 days. Background therapy maximally standardized and included hemodilution, low doses of heparin (if necessary), aspirin, and osmotic diuretics (if necessary). Calcium channel blockers, glycine, piracetam (Nootropil), and drugs with neurotrophic modulatory properties (gangliosides, low molecular weight peptides) was not used.

Comparative analysis of the groups of patients treated with placebo semax and testified about their comparability on demographics, etiology and severity of stroke at the time of hospitalization, resulting in the possibility of a comparative study of the dynamics of clinical and immunological biochemical parameters.

In the clinical analysis found a significant decrease in mortality in the group treated Semax at doses 12 and 18 mg / d group compared to patients treated Semax 6 mg / day or placebo (5, 2.5, 7.5 and 12.5 %, respectively).

It was established as a significant acceleration of the regression of neurological disorders during treatment Semax at a dose of 12-18 mg / day stroke moderate to severe. However, when using low doses of Semax (6 mg / day) no significant differences in the pace and severity of clinical dynamics with "placebo" is not revealed.

Statistical analysis was conducted among patients with stroke of moderate severity, showed a significant acceleration of the regression of focal symptoms to 6th (after treatment) and day 30 of the disease during treatment with Semax at doses of 12 and 18 mg / day compared with placebo and Semax 6 mg / day). The most pronounced therapeutic effect exerted Semax at a dose of 12 mg / day.

Statistical analysis of the dynamics of neurological status showed rapid regression of neurological deficit on the 6th and 30th day in severely ill-treated Semax at doses of 12 and 18 mg / day, compared with those taking a placebo or semaks at a dose of 6 mg / day, and most pronounced positive clinical dynamics was at a dose of 18 mg / day.

Estimation of the dynamics of the individual focal symptoms showed a statistically significant acceleration of recovery of motor functions and speech Semax against application in doses 12 and 18 mg / day as compared to the "placebo" group.

Determining the degree of functional restoration showed an increase in the proportion of patients with good recovery in treatment Semax at doses 12 and 18 mg / day, as compared to the drug dose of 6 mg / day or placebo. The differences were more pronounced in patients with moderately severe stroke, taking Semax in a dose of 12 mg / day, and seriously ill patients who took the drug at a dose of 18 mg / day.

When studying Semax efficiency depending on the timing of the treatment (2-6 or 6-12 hours after the onset of stroke) set benefits of early (within the 6-hour intervals) applying a neuroprotectant. In this case, we determined significantly more pronounced reducing the dynamics of all the clinical scales used.

Thus, conducted a randomized, double-blind, placebo-controlled trial established the safety and tolerability of neuropeptide Semax (ACTH 4-10) in patients with carotid ischemic stroke, his lack of significant side effects. Intranasal administration of Semax a daily dose of 12-18 mg for 5 days, the disease has allowed significantly reduce mortality, improve the clinical outcome of stroke and increase the restoration of disturbed neurological function in patients with different severity of the disease and one for development, including the most severe forms of stroke, caused by embolic and thrombotic occlusion of intracranial parts of the brain arteries. The study of dose-dependent efficacy showed that the optimal daily dose of moderately severe strokes -12 mg, with heavy strokes - 18 mg. The most pronounced neuro-protective effect Semax provides for early application, within a 6-hour interval after a cerebrovascular accident.

Semax: Effects on Brain Activity in Ischemic Stroke

In clinical studies, the effect of Semax on the functional activity of the brain in patients with carotid ischemic stroke found that on the background of the first administration of Semax, 87% of patients with moderately severe stroke EEG cartograms there is an increase in the power of the main alpha range, more pronounced in the intact hemisphere; some patients accompanied by a decrease in the power of slow (delta, theta) range in the projection of ischemic hearth. However, when comparing the statistical average for the group cartograms EEG before and after the first dose no significant changes in the EEG frequency spectrum characteristics of the cardinality. At the same time after the first administration of Semax recorded a significant increase of coherence on the dominant alpha rhythm within the affected hemisphere and between the hemispheres.

Increasing closeness relations alpha oscillations occipital lobes is a favorable prognostic sign, preceding the further normalization of the basic rhythm.

By the 6 th day of stroke in patients with a condition of moderate severity, treated Semax, there is a full normalization of EEG pattern than in the placebo group: a significant acceleration of the alpha-1 rate by an average of 1-2 Hz, a bilateral increase in its capacity to regress hemispheric asymmetry (37.5% - complete).
In patients who did not have in the first study of focal EEG changes (43.5%), to the 6 th day there is no formation of hearth slow delta, theta activity in the projection of ischemic damage, whereas more than half of the patients receiving placebo formed theta focus (4-6,9 Hz).

In 82.3% of seriously ill from the group using Semax already at the first study, recorded early focal increase in amplitude delta, theta activity in the projection of ischemic hearth. At 23.5% determined by unstable frequency of EEG spectra with the advent of bilateral "explosion" of activity in the range of alpha-beta frequencies, indicating that the "irritation" Mesodiencephalic deep brain structures. At the end of treatment in all critically ill Semax registered stable frequency EEG spectrum and reducing the overall energy level of the spectrum. However, in 41.2% of seriously ill focal changes persist throughout the period of acute stroke, which correlates with the formation of persistent focal neurological defect.

When multi-channel recording of SSEP different modalities revealed a predominant influence on the state of nonspecific Semax conductive systems of the brain are more pronounced in patients who were in a state of moderate severity at baseline with favorable prognostic option EEG pattern. The first administration of Semax causes a significant increase in amplitude and decrease latencies medium- and long SSEP components in ischemic and in the intact hemisphere. By the 6th day after the stroke, these trends persist and grow, there is significant normalization of the zonal distribution of long-latency peaks.

Thus, neurophysiological monitoring demonstrates a more rapid and complete normalization of the functional state of the brain in patients with acute ischemic stroke of the carotid during treatment Semax. When analyzing the dynamics of spontaneous bioelectric activity of the brain showed significant positive changes in the frequency-power characteristics and zonal distribution of basic EEG alpha rhythm to the 6 th day of the disease in patients who took Semax (compared to placebo), and a reduction in the local representation of the delta and theta waves in the projection of the ischemic area of the brain, in some cases, to prevent the development of slow activity focus, which is the main electrophysiological marker of cerebral infarction. A significant normalization of medium- and long SSEP components against application semax reflects its favorable action on non-specific conductive system of the brain, which clinically manifested a strong nootropic effect of the drug

Semax: action at vertebrobasilar ischemic stroke

Pathogenic and clinical features of vertebrobasilar stroke caused interest in the study of the effect of Semax with acute focal ischemia stem-cerebellar brain structures. Therefore Semax along with Glycine was included in a randomized, placebo-controlled study of patients with acute vertebralno- basilar ischemic stroke.

Semax intranasally administered in a daily dose of 12 mg irrespective of disease severity. The study protocol, methods and integrated clinical neurophysiological monitoring the operation semax, glycine and placebo were identical. The first introduction of Semax not make significant effect on the general condition of patients, but by the end of treatment (on day 6) in all the examined set a significant regression of brain and focal neurological symptoms was significantly higher on the severity indices in groups of patients who received placebo and glycine.

The positive effect of Semax appears equally at different variants of stroke flow. The results of evaluation of the dynamics of individual focal manifestations show an advantageous effect of the drug on the severity of violations coordinations. Like glycine, Semax most effective for early, within the first 6 hours appointment.

Neurophysiological study found that Semaks has a strong positive effect on the functional state of the segmental structure and sensory systems in the brain compared with glycine. The study of short-stem evoked potentials (ABR) to acoustic stimulation shows that Semax much faster normalizes host the auditory system than glycine and placebo. By the 6 th day of stroke in all patients treated with Semax, showed normalization mid-peak slots N1-N5 and N3-N5 ABR on the side of the ischemic lesion, reflecting the improvement in the functional state of the oral parts of the brain stem. In the group of patients treated with glycine and placebo, a similar positive trend was observed only in the 49 and 23%, respectively.

A more pronounced effect compared with glycine semax provides the parameters of the early component blink reflex, especially in patients with the most rude segmental lesions systems V and VII cranial nerves. By the 6 th day of the disease have been observed almost complete normalization of the latent period of the early component - up (11.7 plus or minus 0.2) ms (at a rate of 10.5-11.5 ms), whereas in patients treated with glycine and placebo, the latent period was (12.35 plus or minus 0.2) and (12.85 plus or minus 0.3) ms, respectively, for the comparability of its values.

At the same time the effect of Semax on the functional state of nonspecific brain structures responsible for the regulation of muscle tone and trophism, is less pronounced than the effect of glycine, which is confirmed by the results of the research center of efferent for polysynaptic spinal pathways and electroneuromyography. Dynamics of time the central efferent and amplitudes of the main muscle building in the paretic limbs in tempo and intensity comparable with the dynamics in the group receiving placebo.

Thus, in the acute period of stroke vertebrobasilar Semax positive effect as glycine, is somewhat less pronounced than with hemispheric ischemia localization (internal carotid artery lesions). However Semax significantly improves reducing the dynamics of brain and accelerates the regression of focal neurological disorders in patients with a stroke of varying severity, especially when it is applied early, and has a normalizing effect on the functional state of the segmental conductor structures and sensory systems of the brain stem. All this shows the feasibility of using Semax in the treatment of vertebrobasilar stroke, including for the purpose of creating a favorable background for reperfusion therapy.

Semax: Mechanisms of Neuroprotection, Research

Immuno-biochemical study of the dynamics of cytokine and CRP levels between the groups treated with placebo and semax shows that all patients mounted an imbalance of pro- and anti-peptidergic systems of the brain with a significant increase in the content of the cerebrospinal fluid triggers an inflammatory response (IL-1beta, TNF-alpha and CRP. by the 3rd day in patients treated with Semax, regardless of the severity and the variant of the disease was significantly more pronounced compared with patients receiving placebo, an increase of the concentration of IL-10 and TNF-alpha are characterized by inflammatory and modulatory action and well as a significant reduction in CRP levels and pro-inflammatory cytokines IL-1beta and IL-8 in the cerebrospinal fluid. The degree of reduction of CRP level has a negative correlation with the degree of growth of the total clinical score at the end of the acute phase of stroke, which makes a reduction of CRP concentrations in the cerebrospinal fluid meaningful marker the effectiveness of the therapy.

When clarifying the effect of Semax on the severity of the anti-inflammatory response of microglia showed a significant difference between the groups in terms of increase levels of IL-10 and TNF-alpha, immunobiochemical other indicators, as well as the total clinical score. In the treatment of Semax dynamics of immune-biochemical status was significantly more positive in terms of prognosis: account increasing levels of IL-10, TNF-alpha and TGF-beta1; a significant reduction in IL-8 and CRP on the background of outpacing growth in the total clinical score for the 6 th day of the disease.

In patients treated with Semax, to the 3rd day of the disease found a statistically significant increase in BDNF concentration in the cerebrospinal fluid of 122%; in the placebo group neurotrophin content was increased by only 89% compared to the first day of the disease. At the same time did not reveal the effect of the concentration of Semax NGF. The selective action of neurotrophins on semax, apparently due to their different nature. The predominant effect of the drug on BDNF confirms its tropism for glial tissue.

The results dynamic research content of secondary products of thiobarbituric acid (TBKRP) in the cerebrospinal fluid indicates the growing concentration in the 3rd day of the disease in the placebo application. In the treatment of Semax the tendency to reduce the content of TBKRP. The difference with the "placebo" group significant with severe stroke.

Study of SOD (superoxide dismutase) concentrations in the cerebrospinal fluid confirms the relationship between the increase in its 3rd day of the disease and the positive clinical dynamics to the 30th day. Semax treatment causes a significant increase in SOD (superoxide dismutase) levels in severe stroke.

A significant decrease in the 3rd day cGMP levels in the cerebrospinal fluid of patients treated Semax, especially in severe forms of stroke.

It is known that the relationship between the reactions of activated microglia, oxidative stress, and the synthesis of cGMP is mediated through a system of nitric oxide. In this regard, it can be assumed that the cause of inhibition of lipid peroxidation processes, the activation of the synthesis of SOD and reduce the cGMP level is inhibition of nitric oxide due to a direct effect of Semax on molecular trigger mechanisms, and its indirect influence through the normalization of the balance of cytokines and increased anti-inflammatory factors . This hypothesis was confirmed in the experimental work carried out on a model of global cerebral ischemia in rats: set significantly lower level of NO as compared with the level in the control group. Preventing the rise of the NO concentration in the background of global cerebral ischemia in the group of rats treated with Semax, accompanied by a significant decrease in the severity of their neurological disorders.

In view of the significant reduction in cGMP levels in the background Semax therapy, as well as experimental data on the effect of cGMP on the processes of calcium current through agonist-dependent channels glutamate the NMDA-receptor analysis of changes in titer autoantibodies to the PCP-binding protein the NMDA-receptors in patients receiving Semax and placebo, showing all surveyed since the first hours after the onset of stroke elevated titers of autoantibodies. Semax treatment causes a significant decrease in titer in critically ill during the period from 6 hours to 3 days of the disease, which may serve as indirect evidence of reduction of the NMDA-receptor dysfunction caused by excess extracellular glutamate.

When studying amino acid neurotransmitter concentrations in cerebrospinal fluid are not significant differences in the concentrations of glutamate and aspartate groups between patients receiving placebo and Semaxs. At the same time revealed an increase GABA levels in patients treated with Semax.

Thus, the chain is Semax metabolic transformations (Scheme 15.3) eliminates cytokine imbalance due to significant reduction in the level of inflammation inducers and increase the content of anti-inflammatory and neurotrophic factors, which leads to inhibition of the local inflammatory response and provide trophic improving brain. Apparently, this is the result of the inhibition of nitric oxide generation and further - increasing concentrations of SOD and LPO inhibition of cGMP synthesis processes. Reducing production cGMP causes changes in activity of glutamate receptors that can be influenced by the level of the whole of glutamate excitotoxicity. Metabolic transformation induced Semax, in fact constitute a closed circuit of related reactions, which may be one of the explanations for the long after-effect of the drug.

Of particular importance is the evaluation of morphological "results" revealed metabolic changes. Morphological damage criterion has been selected concentration of N-acetylneuraminic acid which is one of the major degradation products of neuronal membranes. The study identified the prevention of raising N- acetylneuraminic acid in the cerebrospinal fluid of patients with moderately severe stroke and a significant decrease in its concentration in critically ill during treatment Semax, which confirms the neuroprotective focus metabolic effects of the drug. Ring circuit Semax induced metabolic reactions affect all the basic mechanisms of long-term effects of ischemia, which underlines the prospects of using neuropeptide regulators for the purpose of neuroprotection and justifies further search for effective remedies.

Comparative analysis of the effects of Semax depending on the timing of initiation of therapy shows that the early introduction of the drug (in the 6-hour interval) normalization of immuno-biochemical pattern is more pronounced and correlated with early increases the total clinical score (on the scale Orgogozo and Scandinavian) and recovery acceleration disturbed neurological function (the index of Barthel)

Semax: mechanisms of neuroprotection

In studying the mechanisms of neuroprotection Semax in brain acute focal ischemia patients Semax was appointed at doses of 12 mg / day of moderate severity in stroke and 18 mg / day in severe stroke within 5 days; Criteria for inclusion of patients in the study, methods and schemes of clinical observation and standardized therapy were identical presented in the chapter "Semax: efficiency in the carotid ischemic stroke."

Immuno-biochemical study included determining the concentration of the inflammatory response triggers: IL-1beta, TNF-alpha and IL-8; the main marker of inflammatory reactions - CRP; anti-inflammatory cytokines IL-10 and TGF-beta1; neurotrophins NGF and BDNF; secondary content of LPO products, SOD, cGMP, N-acetylneuraminic acid and neurotransmitter amino acids (glutamate, aspartate, glycine and GABA) in the cerebrospinal fluid; and phencyclidine titer autoantibodies to glutamate-binding protein in the blood serum of NMDA-receptors.

Mexidol Discussion

The fact that the spectrum of activity mexidol wide enough - you know, perhaps everyone, but quite often it can be found in the "Psycholeptics" and if even deeper - it turns out that this is an atypical :) anxiolytic effect of the drug is orally isolated comes later a few days, and by the end of the week to the fore quite clearly anxiolytic effect, really like something on sibazone effects, but at the same time without the characteristic for the database side and side effects, so to speak, effects. When taking the drug inside many initially reported on the phenomena of anxiety and agitation, which is associated with dopamine positive aspect of the drug. Gradually, these symptoms are not expressed, and comes to the fore psychoactive effects of the drug, a similar effect is strong enough to phenibut, which is associated with many additional features Mexidol. Once at pirlindola of application in the first week of the course was enough Mexidol single dose of about 0.5 g per day ... very effective psychotropic drug. It should also be noted that Mexidol is the only drug that has a beneficial effect on people with disabilities who have been their due encephalopathies associated with artisanal production of narcotic drugs with the use of potassium permanganate; and I see its positive effect on patients with malignant tianeptinovoy substance - it is important to consider possible to someone this drug will prolong life, or at least partially restore sanity after "treatment" coaxil, which, as we know, in large doses acts as survektor (amineptine ) - an antidepressant, which stands in the list of drugs on a par with cocaine and heroin because of the powerful narcogene potential. Hyperstimulation of dopamine receptors to blame - the main reason euphoric action "safe" tianeptine, but not the only one. Mexidol should take its rightful place in the list of psychotropic drugs.

Mexidol - nootrop no longer, but rather anxiolytic, or "other medications" In exchange application, as I mentioned earlier, it provides ample mexidol pronounced anxiolytic effect, along with other types of activities inherent to the drug. And most importantly - it really enhances the action of the database. I would say "change for the better": hidazepam on background mexidol becomes more tranquilizing and not activating, and interesting combination mexidol with Imovane - significantly reduces the side effects of the latter, in particular, even some fading characteristic bitter taste in the mouth in the morning.

From personal experience with, including on itself, I can say that as an anxiolytic mexidol is effective, not even the smallest observed anxiolytic action. The attribution of this action he was not more than a publicity stunt. If you read the instructions for its use, so it's just a miracle cure - cures all, no side effects, can be used for all occasions ... but it does not happen.
In fact mexidol just a derivative of vitamin B6, with the theoretically possible, but hard to verify in practice the antioxidant effect. In general, if the crappy price and efficiency - something useless and unnecessary.
The truth is, I have an interesting observation of using mexidol patient with late dyskinesia, in which the reception mexidol rapidly deteriorating condition may dopaminergic drug has some effect.

It speaks only of individual sensitivity: and when receiving mexidol marked excitement and svego kind of "restlessness" in the first days of therapy, which is apparently associated with increased levels of dopamine; effect of the drug develops gradually, and anxiolytic effect appears after a few days - there is an analogy with afobazole necessary time to the central nervous system "adapted" to the drug, well, we should not forget that the anxiolytic effect - it's not tranquilizing in the full sense of the term, as in the database and more selective and notes on the background of nootropic activity. Here at phenotropil has also anxiolytic effects: lol: Mexidol - is another. Pts. well with pirazidol as synergistically enhances the positive effect on cognitive function, removes hypoxia. The anxiolytic effect in mexidol profile - selective, and not the main, but as you progress through the course sta¸t quite pronounced. Of course, it's not the drug that should be used in advanced or severe cases, when in the course are mirtazapine, imipramine, sibazon, Phenazepamum and so on. It is a soft little toxic drug more nootrop-anxiolytic. The anxiolytic effect of his weaker than phenibut, but has its advantages and, if properly used, in certain cases, the mexidol shows its best side, but when it is appropriate to include this drug in the scheme, unfortunately, very few people know. And it's not a "panacea" - the manual describes the properties of the drug due to the strong antioxidant effect and antioxidants affect the body very much, that's why so much in the instructions. Mexidol rarely used in isolation - it is included in the scheme, kgda necessary, but how it can be nootropic and give so little course.

Compare mexidol with vitamin B6 - is at least incorrect - these substances are also similar as pyridoxine with Pyritinol (the latter even is really two pyridoxine molecules connected by disulphide bridge, and it is quite different from pyridoxine PM, not to mention the mexidol). And where does the advertising? Everyone knows that drug ANY attempt to provide the best in the world - not necessarily firmly believe in what they say, and Mexidol interested not only in our country, but also abroad.

Of course, if the diarrhea neurologist prescribe diazepam as enterosorbent, the result is a little bit not one that was expected, but the blame for this drug is meaningless. There are cases where mexidol effective, but there are cases when his appointment may even worsen the situation. I watched a variety of answers to mexidol patients, and it was not properly administered any problems. This is not a database, and it will not give a tranquilizing effect of diazepam, but can demonstrate a special selective anxiolytic effect, where there is no such toxicity as in the database, not to mention addictive. If you stand still, nothing will happen, and now synthesized new and new medicines, the effect of many of which are not shown, but they are, as everyone knows, which is the same database there are a variety of reactions, not to mention the blood pressure, which sometimes required several months to pick up the "working" a drug that would be effective, do not cause allergies and are discharged to the destination, not as horrible.

And when I see the obvious improvement in patients with toxic encephalopathy caused by the use of substitute drugs containing manganese after the course Mexidol therapy, I can not agree with this (!) And knowing about the side effects of nootropics, I give this link and ask to read who have mental and other negative phenomena are the treatment nootropics, and side effects themselves nootropics like drugs (PE common to all drugs, but some PE at nootropil observed in a certain category of patients, and there it is said clearly, and it is possible to draw conclusions on the the appointment of nootropics certain groups of patients at least in theory), and please pay attention to PE mexidol that in practice there are generally very rare.
From this it is clear that the PE neuroprotective agents, particularly piracetam, etc. by the National Assembly are found mainly in psychiatric patients to certain diseases, patients and themselves from PE nootropics minimal, especially in mexidol action which, though not proven, but it is present and quite pronounced, and with a minimum of PE. The drug is used for many years and has proven itself well, but when, who, why, what, etc. give the drug - to decide a doctor, not a cure.

And this is one of the reasons why I do not recommend even things like Afobazol - yes, I see that Afobazol well helps people healthier, but also see how it affects people with different symptoms: how many patients - so many reactions to the drug.
And single reaction More about anything do not say - even in the instructions to vitamins often write: "Do not recommend this drug to other people, even if it helped you," and in the same way we can say: "If you have a negative reaction to this drug, do not tell all his friends that it is a placebo, because it is only your individual reaction to the drug. "

The electrical properties of neurons

Physiologist Dr. Doping tells about neuronal properties, action potentials and the cytoplasm of nerve cells.

Signal is transmitted between neurons in specific structures, called synapses. The transmission of information at the synapse is due to release chemicals, that is, the chemical principle. As long as the information remains inside the nerve cell transmission is electrically due to the fact that the nerve cell membrane, are subject to special electrical impulses - action potentials. This electric current short steps, they are roughly triangular in shape and run on the membrane of dendrites, the neuron axon to the body and eventually reach the synapses.

You can compare the action potentials with a binary computer code. In the computer, as is known, all the information is encoded by the sequence of zeros and ones. Action potentials - is, in fact, edinichki that encode all of our thoughts, feelings, sensory experiences, movement and so on. Once connected to the correct place of neural networks, and feeding on the nerve cells of this kind of electrical impulses, we can make a person feel, for example, positive or negative emotions, or cause any sensory illusions, or manage the work of the internal organs. This, of course, is a very promising branch of modern neurophysiology and neuro-medicine.

In order to control the action potentials, you need to understand where they come from. In principle, action potentials can be compared with the situation when you're using an electric torch applying signals to his friend on the other side of the river. In other words, you press the button, the lamp flashes and on some secret code you have something to pass. In order to make your flashlight working within the battery need, then there is a certain energy. Nerve cells in order to generate an action potential, should also possess a charge of energy, and this charge is called the resting potential. It exists, it is inherent in all nerve cells and is approximately -70 mV, ie -0.07 V.

The study of the electrical properties of neurons began a long time ago. What is present in living organisms electricity, realized during the Renaissance, when they noticed that the frogs' legs twitch from electric shock when they realized that the torpedo emits energy flows. Next was the search for techniques that would have seriously come to the nerve cells and see what electrical processes taking place there. Here we must thank the squid, because squid - it is such a wonderful animal, which has a very thick axons. This is due to his lifestyle: he has a fold-gown that cuts and throws the water, there is a jet momentum and squid moves forward. To a lot of muscle mantle decreased energy and at the same time, we need a strong axon, which immediately would all this muscle mass momentum transfer. Axon has a thickness of 1-1.5 mm. In the middle of the XX century learned to allocate it, paste into a thin electrical wire, measure and record those electrical processes that occur. Then it became it is clear that there is a resting potential and action potential.

The principal breakthrough occurred at a time when the invented glass microelectrodes, ie learned to make very thin glass tubes, which are filled in brine, for example KCl. If a tube very carefully (it should be, of course, do under the microscope) to bring to the nerve cell and pierce the membrane of a neuron, the neuron is a bit dispute, continues to operate normally, and you see what's inside the charge and how this charge changes when transmission of information takes place. Glass microelectrodes - is the underlying technology that is used today.

Toward the end of the XX century there was another way, it is called patch-clamp, when a glass microelectrode not pierces the membrane, and very carefully to her fed, piece of membrane sticks, with a very small cell area of the membrane is analyzed, and you can watch how work For example, individual protein molecules such as the various ionic channels.

The use of these technologies has allowed to begin to understand the origin of the resting potential, where does the charge inside the nerve cells. It was found that the resting potential is primarily due to the accumulation of potassium ions. Electrical processes in living organisms differ from those electrical processes that occur in the computer, because the physical electricity - this is mainly the motion of electrons and in living systems - the movement of ions, that is, charged particles, especially ions of sodium, potassium, chlorine, calcium. This basically provides four different electrical phenomenon in our body: and in the nervous system and the muscles, and the heart - it is a very important part of modern physiology.

Cogitum, Semax, Phenylpiracetam, Picamilon are essential for awaking brains.

When they began to analyze the composition of the cytoplasm of nerve cells, it was found that in the cytoplasm of neurons compared with an environment rich in potassium and low in sodium. This difference arises from the work of a special protein molecule - sodium-potassium pump (or sodium-potassium ATPase). It must be said that the sodium-potassium pump is located on the membranes of all cells because live cells are arranged so that they require an excess of potassium within the cytoplasm, for example in order to work properly, many proteins. Cells exchange intracellular sodium for extracellular potassium is pumped potassium, sodium is removed from the cytoplasm, but this does not change until the charge, because the exchange of more or less equivalent. In normal cells, not nerve, in an excess of potassium, but no charge is not how many positively charged particles, so many negatively charged; is, for example, potassium, chlorine or various organic acid anions.

To ensure that the system has acquired a negative charge, the following occurs. At some point the neuron maturation on its membrane appear constantly open channels for potassium. This protein molecules, and in order that they appear, must earn the corresponding genes are constantly exposed to potassium channels allow potassium out of the cytoplasm, and he goes, because inside it about 30 times higher than outside. It works well-known law of diffusion: the particles (in this case, potassium ions) come from a place where a lot of them, where they are few, and potassium begins to "run away" from the cytoplasm through the constantly open channels specifically for this device.

Banal response to the question "How long it will escape", it would seem, should read: "As long as the concentration is on par", but it is somewhat more complicated, because the potassium - a charged particle. When one runs potassium inside the cytoplasm remains its lone pair, and the cytoplasm acquires a charge of -1. He fled potassium second - already charge -2, -3 ... As potash runs on diffusion, increasing the internal charge of the cytoplasm, and this negative charge. Pros and cons are drawn so as increase the negative charge of the cytoplasm, this charge was hampering the diffusion of potassium ions, and they go becomes harder and harder, and at some point a balance arises: how much potassium escapes by diffusion, the same part due to the attraction to the negative charge of the cytoplasm. This equilibrium point and is approximately -70 mV, the same resting potential. A nerve cell itself charges and is now ready to use this charge, in order to generate action potentials.

When they began to study the origin of the action potential, then we noticed that the cells awakening that it generated the momentum needed to stimulate her pretty certain force. Stimulus tend to raise the charge within the nerve cells to approximately -50 mV resting potential i.e. - -70 mV, and a so-called trigger threshold action potential - somewhere -50 mV. If the charge to raise to a level neuron like waking up: suddenly it appears a very large positive charge, which comes to approximately 30 mV and then quickly drops to about the level of peace-building, that is, from 0 to 1, and then again to 0. Here it is, the current step, which is further capable of transmitting information.

Where does it come from? Why neuron suddenly woke up and gave this momentum? It turned out that other ion channels work here - not always open, and ion channels with wings. At the time when the charge in the nerve cell reaches -50 mV, these shutters begin to open, starts the motion of ions. First, sodium channel opens, about 0.0001 second in time to enter the neuron portion of sodium ions. Sodium included because, firstly, in its cytoplasm small - about 10 times less than the outside, and, secondly, it is positively charged, negatively charged and the cytoplasm, that is attracted to the plus minus. Therefore, the entrance is very fast, totally, and we are seeing a rising phase of the action potential. Then sodium channels (thousands of channels running simultaneously) closed and open potassium channels, and also from Electro-valves. It's not the ones that are always open, and the channels that have a special protein loop (channel - a cylinder, inside which there is a passage), which opens like a turnstile, and potassium ions are able to get out of the cytoplasm and take out a large amount of positive charge and generally charge in the neuron falls to the level of the resting potential. Potassium at this point powerfully comes out, because we are on top of the action potential, there is no -70 mV, a lot of potassium inside and outside a little, he comes out, it makes a positive charge, and the system is recharged.

The membrane of the nerve cell is organized so that if at one point there was a momentum - and it mainly occurs in the area of synapses, where nerve cell mediator filed - that this momentum can spread through the membrane of nerve cells, and that there is a transfer. Pulse Propagation through the membrane of the neuron - a separate process. Unfortunately, it happens quite slowly - up to 100 m / s, and at this level we are, of course, computers are inferior because an electrical signal on the wire travels at the speed of light, and we have a maximum of 100-120 m / s, it is a little. So we're pretty slow organisms compared to computer systems.

In order to study ion channels, physiologists are special toxins that block these channels. The most famous of these toxins - tetrodotoxin, the poison puffer fish. Tetrodotoxin off electro-sodium channel, the sodium is not included, the action potential does not develop, and neurons signals do not propagate. Therefore, puffer fish poisoning is gradually growing paralysis, because the nervous system ceases to transmit information. In a similar action, only softer, have a local anesthetic such as Novocain, which are used in medicine to very locally to stop the transmission of the pulse and not to run pain signals. In order to study the neurons, using animal models, to record human nerve cells can be only very special occasions. During neurosurgical operations there are situations when it is not only permissible but also necessary. For example, in order to accurately enter the zone which is to be destroyed, for example, in some chronic pain.

There are ways to record the electrical activity of the human brain more totally. This is done during the registration of EEG, there are simultaneously recorded total action potentials of millions of cells. There is another technology, it's called technology evoked potentials. These technologies complement what we are given tomographic studies, and allow fairly complete picture of the present electrical processes that takes place in the human brain.

Depression: Causes, Biochemistry, What to do?

Every person in life there are times when it becomes very bad. At times, this state lasts more than one week, and substantially complicates the normal flow of life. Today we talk about depression, its stages, from the banal to the temporary differences between the doldrums, its biochemistry, and what to do?

Philosophy of depression

Almost everything in our world is cyclical, wave character. Birth and death, summer and winter, day and night. In nature, there is not always unhappy or happy people. However, much solves the person's attitude toward the situation. It is this attitude and shifts the balance, and it turns out that one person forever miserable, gloomy and sad, and the second, which is approximately the same appearance and social status, and perhaps even worse, happier. The differences between them in nature! You can also like Phenibut.

It is clear that there are different cases, if the first broke his hand, but was preparing for a mega important competitions, the attitude to the situation it is more difficult to change. Because such cases are dramatic films and books. And also has a fun man that all trolls its gypsum and laughing all around tells how he broke it, and this is a subject for comedy.

In general, try, whenever possible, a positive attitude to everything going on around him.

Causes of Depression

As for the causes of depression, their gobs. In general, they are divided into external and internal.

Outside it's just the injury, death, dismissal, parting with their halves and any other bad phenomena that can befall a person as a bolt from the blue. Even in the morning it could be fine, and in the evening will begin to develop severe depression. Such causes of about 65%. Of which, incidentally outright negative, which is difficult to treat positively, much less. One thing to hand was amputated and quite different: "I can not pay the loan, collectors call, how it's complicated." To understand where the pure negative, and where he plays the role of human relationship, you need to look at the problem on a universal scale. This was discussed in the release of about NLP. Introducing our beloved planet with views of the cosmos and the cry of the soul of any point of the planet. If what you hear is a smile, it's not a problem.

Internal arise from the disruptions in the body: infection, post-disease, the consequences of drug addiction or alcoholism. Even the banal chronic lack of sleep or poor nutrition may eventually lead to depression. Read the history of how hard some peel with Phenibut, Phenazepam or Lyrica. Later in the biochemistry of depression, we will touch on hormones and neurotransmitters.

What is depression?

There are many classifications of depression, not to convert everyone in the lecture and list definitions based on the opinions of various scientists, will focus on distinctive features. So:

• 1. Fatigue, weakness, lethargy lasting more than a month. It is particularly noteworthy continuous nature. A week may experience weakness and totally healthy person, because of a cold, bad weather, atmospheric pressure and other reasons.
• 2.Bad mood more than 2 consecutive weeks. Week bad mood, then a couple of days everything is super, and again everything is bad - not depression. In the morning, bad, cool in the afternoon, the same thing.
• 3.Loss of pleasure in previously favorite activities. That's like you poking around in cars or on Monday, Wednesday and Friday to play the guitar, but now everything seems meaningless, and there is nothing new that fascinates you - depression.

It is believed that only two of these three characteristics, coupled with the secondary, such as: impenetrable pessimism, suicidal thoughts, feelings of fear or helplessness, decreased self-esteem. The more matches - the more the alleged depression.

Biochemistry of Depression

Thus, an explanation of depression, in addition to those which we have all heard enough: lack of serotonin, dopamine and norepinephrine (called monoamine hypothesis). Besides these, the most interesting are:
1. Changes in synaptic transmission. We know that when people say to eat fish, it gets tryptophan, an amino acid such. It enters the blood and into the brain, using enzymatic reactions becomes mediator serotonin. Any calcium ions accumulate in the presynaptic membrane, they catalyst forced to free serotonin and other mediators substrates through phosphorylation by protein kinases.

In short, the lack of the garbage that is written in the mineral can lead to depression.

2. Violation of the reuptake of neurotransmitters. Original transport proteins inactivate neurotransmitters from the synaptic cleft into presynaptic membrane. Ie, the desired substances are produced, but does not work as it should, the body removes them, is like throwing a half battery charge.

3. Changes in monoamine receptors. There are less clear earlier serotonin receptors have been more, but here you drunk, and they became smaller. It used to be 3 cock of the barrel with a pick, and now pours 1. Mediators, as it were less.

How to get out of depression

Truly ingenious answer - not to get into it! So once again we recall, evaluate their problems objectively, do not be petty, do not worry about nothing. Dismissed from his job, broken car, no money - it does not matter, the main thing is not to whine, but to correct the situation. Serious real deep depression overcome physician time and effort of the person.

On the basis of biochemistry, for the destruction of social phobia and depression is canceled starting to communicate with people, preferably new, normally eat and sleep, physical activity, ideally, go to the sports section, there will be new acquaintances. So we employ serotonin and endorphins. To connect dopamine - set goals and achieve them.

There is another very clever phrase, over which is periodically to reflect: "Depression is not to win at the former way of life and thinking." How much would you antidepressants did not eat, they give only a temporary effect.

Therefore, we are changing the way of life! Force yourself to think "differently". Otherwise, all else being equal, will return to the starting point quickly.

Next, we present a list of what can improve the state of health without the pharmacology of many things you probably never heard of.

• 1.Do not sleep one night! Sleep deprivation not kill serotonin, if not abused, but good will pump dopamine. Around 60% of the depression weakened markedly. Go to the club, walk, make new acquaintances - to increase efficiency.
• 2.Look at the bright things. If finances allow, you can even buy. Celebrate the dawn, sunrise or sunset spend - the mood will improve!
• 3.You can add to the diet of sugary foods. Consuming it periodically in small quantities. Watch your weight, the extra fat increases the production of cortisol and reduces testosterone, which also worsens the mood.
• 4.Travel. Changing the environment gives rise to the development of a variety of substances in our body, such as endorphins, acetylcholine, dopamine, which really improves the overall well-being. If the trip is pleasant, or at least not negatively. And do not idealize, then there will be a risk of inflated expect.
• 5.Do not twist the Statement which you are unique, fantastic and a good kind person that you underestimate the world. Or do not fall into despair, you are nobody. Each person has their own pros and cons, the only difference in their number and specific weight of each.

Once watched a video of one psychologist, he told me about a very cool thing, how to find balance in their self-assessment: not stuck-up (depression on the risk of inflated expectations) or always sad (depression from reduced self-esteem).

So, he said, that they are a student with friends, deliberately lowered himself self-esteem, no matter how low or high it may be. They put themselves fake rotten and crooked teeth and got acquainted with the girls, but when you have such a radiant smile to everyone around you, your self-esteem plummeted. When they were still able to at least someone sit in a cafe, they went to the toilet, all filmed and watched the reaction of the girls.
Worsened opinion of themselves artificially, when returning to the normal state we reappear force and more honest picture of yourself.

Caffeine - Budget Stimulator

One of the most popular and perhaps the most accessible in the world of stimulants, which is used for centuries in the form of coffee or tea. Hello everyone! Today we talk about caffeine. About its principles of action, effective dosages and the like.

Some people say they can not wake up without coffee, can not be involved in the work, in fact, they can not decaffeinated. A method of transporting the substance, whether it is an energy drink, coffee, tea, or other forms, play a secondary role. Caffeine really invigorates, resulting in feelings. But this is only the subjective consequences of taking this supplement, all the fun is happening at the level of effects on the body.

Caffeine is extremely effective not only in everyday life, to wake up or fall asleep, but also in medicine, sport and even to improve intellectual abilities. Caffeine’s methods of application, starting from the banal beverage to capsules, tablets and even ampoules for injection through a syringe. However, as in absolutely any substance, caffeine, there are minuses. You can use Cerebramin.

How does caffeine act

The supplement is very popular and has a huge research base, we proceed:

• 1.Increase pressure. It so happens that there is a weakness, it is hard to think, there is no concentration, drowsiness, often it is due to the reduced pressure. Incidentally, in the winter time, the pressure is usually lower than in the summer. Caffeine can help in this! ... Or hurt, if a person has high blood pressure initially. To increase pressure effective dosage of 3 mg / kg body weight.
• 2.The heartbeat quickens. More blood passes through the body per unit of time, this is the same tone. Then you just do not overdo it, like other stimulants, if a person initially high pulse, the receiving stimulants will hurt and you need as soon as possible to begin to train the heart.
• 3.Action on hormones: adrenaline, cortisol, testosterone, adenosine. This does not mean that everything else caffeine is not active, this means that less accurate data regarding the following hormones.
• 3.1.Adrenalin. The main stress hormone, ancient doping is activated under the influence of a direct threat. The dosage of 6 mg / kg (which is very high) body weight increase the concentration of adrenaline by 40-50% in the elderly, but there is evidence that young people increase reaches 500%. There is also a slight increase in noradrenaline.
• 3.2.Cortisol. This hormone, which is extremely useful in war or famine, and bad in everyday life. He quickly destroys muscles, if they do not use or promote the growth of adipose tissue. In general, the concentration of cortisol rises compared to placebo level. Particularly strong increase occurs after physical exercise. In intellectual work, increased slightly.
• 3.3.Testosterone. Hormone brutal men, responsible for male traits, and also directly proportional interconnected with neurotransmitters such as serotonin and dopamine. The more testosterone - the higher they are, and vice versa. There are also studies that after nat. training testosterone placebo group was 15% higher on average caffeine group by 21%.
• 3.4.Adenosine. Caffeine is an antagonist of adenosine compounds, which means that caffeine has the opposite effects of adenosine. Namely prevent drowsiness. Adenosine is activated when a person or exhaustion, tired, this nucleoside drives man to sleep, play, relax .. Caffeine off the connection.
• 4.Caffeine as a growth factor receptor. Serotonin. The hormone of pleasure and joy. Its level increases, moreover, caffeine is a kind of cement for the construction of serotonin receptors, protein compounds, there is evidence that the same is observed in the context of such receptors: serotonin, nicotinic, muscarinic, GABA and dopamine. True crazy used dosage of 100 mg / kg.
• 5.Working memory. Improves cognitive performance. Conducted intelligent testing, where people are divided into 3 groups. Night and morning, they had nothing to eat, and in the morning, the group 1 received placebo, the second - 75 mg of caffeine, the third - 75 mg caffeine + glucose 75g (sweet). Best of all coped with the tasks 3rd group. Already once said that eating carbohydrates for breakfast, oatmeal etc. for the excellent work of the brain, that's proof.
• 6.Reducing fatigue. On this point it was carried out research among its multi-pronged sporting cyclists. One received a placebo, the other - 240 mg of caffeine. The results were such that caffeine 5.4% contributed less tiring.

The damage and the danger of caffeine

• 1.Addiction. Indeed, long-term use may appear small dependence on caffeine. This is not fatal, but can occur at any time insomnia. This occurs due to the constant action of inhibiting adenosine, which is designed to reassure the time. His settings slipping, which leads to unclear biorhythms. In this case, you can chop off treacherously intake of caffeinated substances can be for a week, gradually withdraw to 0. All the problems have to pass a few days.
• 2.Tolerance. It is, but rather psychological. One simply becomes accustomed to constant stimulation and it begins to seem that "before the Energy drink worked better."
• 3.Circulatory system problems. Not Recommended intake for people with high blood pressure or tachycardia. Even if a person is healthy, regular intake of caffeine in combination with lack of sleep, constant fatigue, which is docked stimulants make a person sick.

The effective dose of caffeine is about 6.4 mg caffeine / kg body weight per day. For 1 time it is not advisable to take more than 4 mg / kg.

Fanatics of mega-stimulation can be combined with taurine, DMAA and other stimulants.

Bottom Line:

• Caffeine - a great stimulant available. Simultaneously simple and effective.
• Take whenever, as acts through 10-40 minutes. Daily dosage of not more than 6 mg / kg body weight. For the purposes of brain bleeding, you need to take with something sweet (but not overeat).
• It operates largely through catecholamines (adrenaline, noradrenaline), and adenosine.
• Caffeine combines with other stimulants, of course, the dosage is reduced.