The effects of prenatal hyperhomocysteinemia on the formation of memory and the contents of biogenic amines in the rat hippocampus

We evaluated the long-term neurophysiological effects of prenatal hyperhomocysteinemia (HHC) in mature female rats whose mothers received an oral methionine load daily from the fourth day of pregnancy to delivery. We have shown that after the experimentally induced prenatal HHC in mature female rats, shortterm and long-term memory were disrupted. These changes were observed in the absence of exogenous methionine intake and after recovery of normal values of homocysteine in the serum of rats in comparison with the level detected immediately after birth. A significant reduction in the concentration of noradrenaline, serotonin, and 5-hydroxyindoleacetic acid in the hippocampus of mature female rats subjected to prenatal HHC was also found, which may be one of the causes of their cognitive impairment.     

Activation of a latent respiratory motor pathway by stimulation of neurons in the medullary chemoreceptor area of the rat

Previous studies have demonstrated that during respiratory stress (hypercapnia and hypoxia), a latent crossed respiratory pathway can be activated to produce hemidiaphragm recovery following an ipsilateral C2 spinal cord hemisection. The present study investigates the effects of ventral medullary chemoreceptor area stimulation by microinjection of (1S,3R)-aminocyclopentanedicarboxylic acid (ACPD), a glutamate metabotropic receptor agonist, on activating the latent pathway following left C2 spinal cord hemisection in rats in which end-tidal CO2 was maintained at a constant level. Experiments were conducted on anesthetized, vagotomized, paralyzed, and artificially ventilated rats in which phrenic nerve activity was recorded bilaterally. Before drug injection, the phrenic nerve contralateral to hemisection showed vigorous respiratory-related activity, but the phrenic nerve ipsilateral to hemisection showed no discernible respiratory-related activity. ACPD (1-100 nl, 1 mM) was injected directly into the region of the retrotrapezoid nucleus (RTN), a known medullary chemoreceptor area. Microinjection of ACPD into the right RTN increased respiratory-related activity in the right phrenic nerve (contralateral to hemisection). ACPD (>5 nl, 1 mM) microinjection also significantly induced respiratory recovery in the phrenic nerve ipsilateral to hemisection in a dose-dependent manner. The present study indicates that respiratory recovery can be achieved by stimulation of respiratory circuitry without increasing CO2 levels.     

Changes in sleep-wakefulness in the medial preoptic area lesioned rats: role of thermal preference

Changes in sleep-wakefulness (S-W) were studied in adult male Wistar rats, along with body temperature (T(b)), locomotor activity (LMA) and thermal preference, after the lesion of the medial preoptic area (mPOA) with N-methyl-D-aspartic acid (NMDA). The sleep was decreased after the lesion of the mPOA, but there was recovery when the rats were given freedom to stay in an ambient temperature (T(amb)) which they preferred. When given a choice between three T(amb) (24, 27 and 30 degrees C), the rats preferred 27 degrees C before the mPOA lesion, and 24 degrees C during the initial days after the lesion. There was a shift in the thermal preference to 30 degrees C, on the fourth week after the lesion, which coincided with the considerable recovery of sleep. The preference for higher T(amb) probably helped to improve sleep, as T(amb) of 30 degrees C is known to promote sleep. When the lesioned rats were not given the freedom to select the T(amb), there was no recovery in sleep. The mPOA seems to be essential for increasing the durations of slow wave sleep (SWS) episodes, especially the light SWS (S1), as they remained shorter than the pre-lesion value, even when the rats were given freedom to stay in a preferred T(amb). The homeostatic recovery of sleep, especially the night time sleep, resulted in the disruption of circadian sleep rhythm. But, the LMA, T(b) and thermal preference maintained their diurnal variation. T(b) and LMA were elevated after the mPOA lesion and they remained so till the end of the study.     

The efficacy of antioxidants in functional recovery of spinal cord injured rats: an experimental study

A total of 30 female Sprague-Dawley rats (180-220 g) subjected to spinal cord injury (SCI) were divided into three groups of ten rats each. Group 1 served as control (SCI + Saline), Group 2 received daily dose of ascorbic acid 2,000 mg/kg body weight and group 3 rats received alpha tocopherol daily with the dose of 2,000 mg/kg body weight for 14 days. The Spontaneous coordinate activity (SCA), Basso, Beattie, and Bresnahan (BBB) and Tarlov locomotor scores were used to assess functional recovery of SCI rats. Compared to group 1, group 2 showed statistically insignificant improvement in the SCA, BBB and Tarlov scores at the end of the study. Compared to group 1, group 3 showed statistically significant improvement in the SCA (P < 0.001), BBB (P < 0.001) and Tarlov (P < 0.01) scores at the end of the study. In conclusion, the administration of alpha-tocopherol enhances the reparative effects against SCI and it is more effective than ascorbic acid.     

Analysis of the Inhibitory Effect of Oestradiol on Functional GABA/5-HT Relationship in the Rat Suprachiasmatic Area

The purpose of this study was to test the capacity of oestradiol to modulate the stimulating effect of a-aminobutyric acid (GABA) on serotonin (5-HT) metabolism, previously described in the Suprachiasmatic area of the male rat. After an in vivo stimulation of GABA transmission by systemic administration of a GABA-transaminase inhibitor (amino-oxyacetic acid) or a GABA_B agonist (RS-baclofen), the 5-HT metabolism was studied in the Suprachiasmatic area of ovariectomized, and ovariectomized oestradiol-treated rats. Amino-oxyacetic acid or RS-baclofen treatment increased the endogenous content of 5-HT in the Suprachiasmatic area of males and ovariectomized rats. These two treatments were without effect in ovariectomized oestradiol-treated rats. GABA transmission stimulation induced by amino-oxyacetic acid treatment failed to affect the release and synthesis of 5-HT in ovariectomized oestradiol-treated rats while it increased these two parameters of 5-HT metabolism in the Suprachiasmatic area of male and ovariectomized rats. To investigate the main target of oestradiol effect, comparative studies of the serotoninergic and GABAergic metabolism in the Suprachiasmatic area were performed in the three experimental groups. Under our experimental conditions the endogenous 5-HT metabolism was similar between ovariectomized and ovariectomized oestradiol-treated rats. Nevertheless, 5-HT metabolism was higher in the two female groups than in the male group. Neither GABA metabolism nor GABAergic response to GABA-related drug treatment differed between ovariectomized, and ovariectomized oestradiol-treated rats. However, the turnover of GABA was higher when compared to the two female groups. It is concluded that the lack of 5-HT responsiveness to GABA transmission stimulation in ovariectomized oestradiol-treated rats was not related to an effect of oestradiol on 5-HT metabolism or to an effect of the steroid on GABA turnover. Furthermore, our results suggest a sex difference in the activity of serotoninergic and GABAergic systems in the Suprachiasmatic area.     

NIH-3T3 fibroblast transplants enhance host regeneration and improve spatial learning in ventral subicular lesioned rats

Transplants, besides providing neural replacement, also stimulate host regeneration, which could serve as a powerful means to establish functional recovery in CNS insults. Earlier, we have reported the H3-GFP transplant mediated recovery of cognitive functions in the ventral subicular lesioned rats. In the present study, we demonstrate the efficacy of a non-neural fibroblast transplants in mediating host regeneration and functional recovery in ventral subicular lesioned rats. Adult male Wistar rats were lesioned with ibotenic acid in the ventral subiculum (VSL) and were transplanted with NIH-3T3 fibroblast cells into CA1 region of the hippocampus. Ventral subicular lesioning impaired the spatial task performances in rats and produced considerable degree of dendritic atrophy of the hippocampal pyramidal neurons. Two months following transplantation, the transplants were seen in the dentate gyrus and expressed BDNF and bFGF. Further, the VSL rats with fibroblast transplants showed enhanced expression of BDNF in the hippocampus and enhanced dendritic branching and increased spine density in the CA1 hippocampal pyramidal neurons. Transplantation of fibroblast cells also helped to establish functional recovery and the rats with transplants showed enhanced spatial learning performances. We attribute the recovery of cognitive functions to the graft mediated host regeneration, although the mechanisms of functional recovery remain to be elucidated.     

Does endogenous progesterone promote recovery of chronic sensorimotor deficits following contusion to the forelimb representation of the sensorimotor cortex?

We studied sensorimotor recovery in male, normal-cycling and pseudopregnant female rats following unilateral FL-SMC contusions. Forelimb use (push off before a rear, support against the walls, and landing after a rear) and the foot fault test (foot misplacements during locomotion on an elevated grid) were analyzed from videotapes taken before surgery, and then again on post-surgical days 2 and 36. High endogenous progesterone levels in females at the time of injury did not affect recovery as there were no differences between males, pseudopregnant females and normal-cycling female rats on these behaviors. None of the brain-injured rats recovered symmetrical forelimb use between 2 and 36 days after injury (P>0.05) and they also showed foot misplacements (P>0.05) in the foot fault test. Male and female rats with contusions had fewer mean foot misplacements on day 36 than 2 days after injury (P<0.001), indicating that there was partial recovery on this task. These results were taken to show that there were no sex differences in motor deficits caused by unilateral FL-SMC injury. In addition, higher endogenous progesterone levels in females did not protect them from the chronic sensorimotor deficits caused by unilateral FL-SMC contusions.     

Hypothermia elicited by haloperidol in rats with hypothalamic lesions

In a previous paper it was reported that haloperidol plus morphine produces a marked hypothermia, whereas each drug alone had only negligible effects on temperature. A large hypothalamic lesion produced variable hypothermia lasting several days. After the lesion, rats could be classified in two groups: A--those which had marked decreases of colonic temperature (from 3 to 7 degrees C) and B--those which had a slight decrease (about 1 degree C). The administration of haloperidol, which in normal rats has no effect on temperature, elicited in hypothalamic-lesion rats, whether or not they were already hypothermic, a marked decrease in temperature lasting several hours. Rats of group B showed a faster decrease as well as a faster recovery of temperature than those of group A. It was concluded that the hypothalamic lesions produced an effect equivalent to an increase in opioid activity and/or a decrease in dopaminergic activity.     

Differential and sex-specific effects of kainic acid and domoic acid lesions in the lateral septal area of rats on immune function and body weight regulation

The lateral septal area (LSA) has been implicated in the control of various psychoneuroendocrine processes in the rat. Interactions between the endocrine and immune systems and sex differences in immunity reflect the interdependence of the immune and neuroendocrine systems. Kainic acid (KA) lesions in the lateral septal area not only modify neuroendocrine processes, but also produce a suppression of humoral immunity in female rats. Presently, we have evaluated the effects of neurotoxic lesions in the LSA on the humoral immune response and body weight regulation of male and female rats. Bilateral lesions in the LSA of adult male and female rats were produced by stereotaxically infusing either 0.25 microliters of kainic acid (1.5 micrograms/microliters) or 0.5 microliters of domoic acid (DA; 0.3 micrograms/microliters) into the LSA. In an additional study, LSA lesions using 0.25 microliters of DA (0.6 micrograms/microliters) were produced in female rats only. Sham operations consisted of bilateral injections of 0.9% saline into the LSA. The effects of these lesions on antibody production, following immunization with 100 micrograms ovalbumin in complete Freund's adjuvant, were examined. Blood samples were collected on Days 7 and 14 following immunization. The anti-ovalbumin IgM and IgG antibody titers were measured by an enzyme amplified ELISA assay. As found previously, KA-induced LSA lesions in adult female rats produced an increase in body weight and a suppression of the humoral immune response. However, LSA lesions produced with the neurotoxin DA had a similar effect on body weight but had no effect on humoral immunity. In male rats, neither body weight regulation nor the humoral immune response was affected by KA or DA lesions in the LSA. These results indicate that the effects of neurotoxic LSA lesions on body weight regulation and the humoral immune response are sex specific and further demonstrate that two closely related kainate neurotoxins have differential effects on the humoral immune response, but have similar effects on body weight regulation. Thus, neurons in the LSA of female rats that are involved in the inhibitory control of body weight are susceptible to both KA and DA, whereas neurons in the LSA associated with immunoregulation are differentially affected by KA and DA. Of further interest, a sex difference in DA susceptibility was noted, with male rats showing greater cell loss in the LSA following DA infusions, as compared to female rats.     

Modifications in gonadotropin control and reproductive behavior in the female rat by hypothalamic and preoptic lesions

Effects of small hypothalamic and preoptic area lesions on vaginal cyclicity, ovulation and ovarian weights of female rats were examined. Animals were then gonadectomized and tested for lordosis behavior following injections of estrogen alone and estrogen plus progesterone. Male sex behavior was also measured during daily treatment with testosterone. Relative to sham operated rats, lesions in the dorsal preoptic area produced a significant increase in lordosis behavior, virtual elimination of male sex behavior, and only marginal effects on ovarian function. Animals with lesions in the ventral preoptic area showed constant vaginal cornification, lack of ovulation and significantly smaller ovaries than the other groups. These rats also tended to show more female sex behavior and less male sex behavior than sham operated rats. Animals with lesions in the anterior hypothalamus and dorsomedial hypothalamus showed normal ovarian function and levels of female and male sex behavior comparable to the ventral preoptic lesioned rats. Animals with lesions in the ventromedial hypothalamus tended to show lower levels of lordosis behavior than sham animals but displayed a dramatic and significant increase in male copulatory behavior relative to the other groups. These data indicate a clear dissociation between the neural control of cyclic gonadotropin activity and sex specific reproductive behavior.     

Lipopolysaccharide increases gamma-aminobutyric acid synthesis in medial preoptic neurones in association with inhibition of steroid-induced luteinising hormone surge in female rats

Lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, inhibits gonadotrophin secretion and ovulation in female mammals. The present study was undertaken to examine whether gamma-aminobutyric acid (GABA)-synthesising neurones in the medial preoptic area (mPOA) may be involved in the inhibition by LPS of progesterone-induced luteinising hormone (LH) surge in ovariectomised oestrogen-primed rats. An intravenous injection of LPS (10 microg) at noon significantly increased the content of glutamic acid decarboxylase 67 (GAD67), a GABA-synthesising enzyme, in brain tissues including the mPOA. LPS treatment also significantly increased the number of detectable GAD67-immunoreactive (ir) as well as GABA-ir cells in the mPOA, compared to control rats. The same LPS challenge completely eliminated the steroid-induced LH surge, which was normally induced in control rats in the afternoon. A local injection of muscimol (100 ng), a GABA(A) receptor agonist, into the mPOA also significantly attenuated the LH surge, mimicking the effect of LPS. These results suggest that LPS stimulates GABA synthesis in preoptic neurones, which in turn inhibit the LH surge in female rats. The results also support the hypothesis that diminution of the GABAergic suppressive activity in the mPOA permits the LH surge to be induced.     

Perinatal androgenization prevents age-related neuron loss in the sexually dimorphic nucleus of the preoptic area in female rats

To investigate the effect of perinatal testosterone exposure, which simulates the endogenous testosterone peak, on neuron loss during aging, nuclear morphology was evaluated in male and female rats as well as in female rats treated with testosterone perinatally followed by ovariectomy (TE/Ovx). Additionally, neuronal apoptosis, which occurred primarily at postnatal day 8 (PND8), was identified by in situ TUNEL staining. Neuronal density, nuclear volume, total neuronal number and pyknotic ratio were estimated after HE stain at PND8, middle age and old age. The results showed that age-related decrease in neuronal nuclear volume and total neuron number in the sexually dimorphic nucleus of the preoptic area (SDN-POA) of female rats was significantly diminished by TE/Ovx. The pyknotic ratio in the SDN-POA of female rats at PND8 was significantly higher than that of males, and neuronal death was reversed by testosterone exposure, while no significant difference of pyknotic ratios was observed among male, female and TE/Ovx female rats at both middle and old age. Moreover, the high apoptotic incidence of female rats at PND8 was significantly diminished by testosterone exposure. These results suggest that neuron loss in the SDN-POA during aging may be predominantly determined by perinatal testosterone through modulation of postnatal neuronal apoptosis.     

Hippocampal GluR1 associates with behavior in the elevated plus maze and shows sex differences

The hippocampus is involved in anxiety as well as spatial memory formation and is sexually dimorphic. Female rats typically show less anxiety in elevated plus maze procedure (EPM), a standard animal model of anxiety. Many intracellular proteins, including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 and the cyclic AMP response element-binding protein (CREB), in hippocampus contribute to memory formation. However, less is known about the roles for hippocampal GluR1 and CREB in anxiety. We examined behavior in EPM in male and female rats and obtained hippocampal tissue samples to determine levels of GluR1 and CREB with western blots. EPM results showed that female rats exhibited less anxiety-like behaviors than male rats. Further, behaviors in EPM were significantly correlated with hippocampal GluR1 levels, but not with CREB. Yet, both proteins showed sex differences with lower levels in female rats. These data not only suggest some potential bases for sex differences in behaviors to which the hippocampus contributes but demonstrate that there is a strong association between hippocampal GluR1 levels and anxiety as assessed with EPM.     

Myelin pathogenesis and functional deficits following SCI are age-associated

Most spinal cord injuries (SCI) occur in young adults. In the past few decades however, the average age at time of SCI and the percentage of injuries in persons over the age of 60 have increased. Studies have shown that there is an age-associated delay in the rate of remyelination following toxin-induced demyelination of the spinal cord, suggesting that there may be an age-associated difference in regenerative efficiency. Here we examine for the first time locomotor recovery, bladder recovery, and myelin pathology in young (3 months), aged (12 months), and geriatric (24 months) female rats following contusion SCI. Our assessments indicate that aged and geriatric rats have a delayed rate of locomotor recovery following contusion SCI as compared to young rats. Additionally, aged and geriatric rats have significantly slower bladder recovery as compared to young rats. Examination of myelin pathology reveals that aged and geriatric rats have significantly greater area of pathology and amount of demyelination, as well as significantly less remyelination as compared to young rats following contusion SCI. These data are the first to indicate that there is an age-associated decline in the rate and extent of both locomotor and bladder recovery following contusion SCI, and that age adversely affects the degree of general pathology, demyelination, and remyelination that accompanies contusion SCI.     

Effect of decompression on complete spinal cord injury in rats

To examine whether spinal cord decompression improves functional recovery and decreases lesion volumes in paraplegic (not paraparetic) rats and, if so, at what postoperative time it is most efficacious. The spinal cords of 63 female rats were compressed at T9 with Yasargil clips. Rats were assigned randomly to five different treatment groups of 3 s, 1 hr, 6 hr, 3 weeks, and 10 weeks. Locomotor behavior scoring was based on the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale (Ohio State University, Columbus, OH) motor scores. Comparing five groups, the mean BBB was statistically higher in the 3-s group (P < 0.05). Comparison of progressive changes in BBB in each group revealed statistically meaningful improvement in the 3-s group, too. Spared surface area of spinal cord was 81.5 +/- 4.9% in 3-s group and 10.8 +/- 1.4% in the delayed groups of decompression (P = 0.039). Rats undergoing immediate decompression showed significantly better functional recovery and smaller lesion volumes.     

Lesions in nucleus basalis magnocellularis and medial septal area of rats produce qualitatively similar memory impairments

The functional contribution of nucleus basalis magnocellularis (NBM) and the medial septal area (MSA) to memory was evaluated in two different spatial discriminations. Preoperatively, rats were trained to a criterion level of performance in a simultaneous left/right discrimination on the stem of a T-maze (a trial-independent memory) and a discrete-trial, rewarded alternation discrimination on the arms of the T-maze (a trial-dependent memory). Bilateral lesions were made by injecting ibotenic acid (IBO) into the NBM, MSA, both NBM and MSA, or dorsal globus pallidus (DGP), and by radiofrequency current (RF) in the NBM and MSA. Control rats received operations in which either no current was passed or no neurotoxin was injected. Lesions in the NBM, MSA, or both the NBM and MSA produced a similar pattern of behavioral changes relative to the performance of controls; postoperative reacquisition of the arm discrimination was initially impaired but showed recovery to normal levels, whereas postoperative reacquisition and reversal of the stem discrimination was not impaired (except following the combined NBM and MSA lesion). Lesions of the DGP had no effect on choice accuracy in any discrimination. When the discrimination on the arms was made more difficult by increasing the delay interval during which the information had to be remembered, rats with combined NBM and MSA lesions were again impaired relative to controls and showed no signs of recovery of function. These results provide information about the behavioral functions of the basal forebrain cholinergic system and suggest that pathological changes in certain components of this system can cause disorders of memory.     

Melanin-concentrating hormone is expressed in the laterodorsal tegmental nucleus only in female rats

Melanin-concentrating hormone (MCH) is a neuropeptide originating from prepro-MCH. In male rats, neurons expressing MCH are found in the lateral hypothalamic area and medial zona incerta, as well as, sparsely, in the olfactory tubercle and pontine reticular formation. The wide distribution of MCH fibers suggests the involvement of this neuropeptide in a variety of functions, including arousal, neuroendocrine control and energy homeostasis. In lactating females, MCH is expressed in the preoptic area, indicating sexual dimorphism in MCH gene activation according to the female reproductive state. We hypothesized that MCH is also expressed differentially in the brainstem of female rats. Adult male rats and female rats (in the afternoon of diestrus and proestrus days; ovariectomized; or on lactation days 5, 12 and 19) were perfused between 2 and 4 p.m., and the brainstems were processed for in situ hybridization using a 35S-labeled prepro-MCH riboprobe. As described in males, prepro-MCH was expressed in the pontine reticular formation of females. We also observed consistent prepro-MCH expression in the caudal laterodorsal tegmental nucleus (LDT) of females but no differential expression comparing the various female reproductive states. Using dual-label immunohistochemistry or dual-label in situ hybridization, we found that brainstem MCH neurons coexpress glutamic acid decarboxylase mRNA, the gamma aminobutyric acid (GABA) processing enzyme, but do not colocalize choline acetyl transferase (acetylcholine processing enzyme). Since changes in LDT GABAergic cell activity are associated with rapid eye movement (REM) sleep, our findings suggest that MCH interacts with LDT GABAergic neurons and plays a role in REM sleep regulation.     

Sexual dimorphism in the spontaneous recovery from spinal cord injury: a gender gap in beneficial autoimmunity?

Immune cells have been shown to contribute to spontaneous recovery from central nervous system (CNS) injury. Here we show that adult female rats and mice recover significantly better than their male littermates from incomplete spinal cord injury (ISCI). This sexual dimorphism is wiped out and recovery is worse in adult mice deprived of mature T cells. After spinal cord contusion in adult rats, functional recovery (measured by locomotor scores in an open field) was significantly worse in females treated with dihydrotestosterone prior to the injury than in placebo-treated controls, and significantly better in castrated males than in their noncastrated male littermates. Post-traumatic administration of the testosterone receptor antagonist flutamide promoted the functional recovery in adult male rats. These results, in line with the known inhibitory effect of testosterone on cell-mediated immunity, suggest that androgen-mediated immunosuppression plays a role in ISCI-related immune dysfunction and can therefore partly explain the worse outcome of ISCI in males than in female. We suggest that females, which are more prone to develop autoimmune response than males, benefit from this response in cases of CNS insults.     

Castration decreases extracellular, but increases intracellular, dopamine in medial preoptic area of male rats

Dopamine (DA) is released in the medial preoptic area (MPOA) of male rats in the presence of a female, and it facilitates male sexual behavior. Castration blocks the DA response to a female and the male's ability to copulate. The present experiments examined the effects of castration on (1) basal levels of extracellular DA in the MPOA, using the no net flux microdialysis technique, (2) the response of extracellular DA to amphetamine, and (3) tissue levels of DA. Castrated rats had lower basal levels of extracellular DA in the MPOA, compared with gonadally intact rats; in vivo recovery, a measure of uptake, was not different. This suggests that castration decreases DA release in basal conditions, as well as in response to a female. However, systemic amphetamine injections, which induce DA release, resulted in greater DA release in castrates. Finally, tissue levels of DA were higher in the MPOA, the caudate–putamen and the bed nucleus of stria terminalis of castrates. These data suggest that DA synthesis and storage in the MPOA are normal, or even enhanced, in castrates, and uptake is not altered. The deficit in extracellular levels appears to be related to release, perhaps due to decreased nitric oxide.     

A morphological-histochemical study of neurodegenerative and regenerative processes in flexor and extensor collaterals of the sciatic nerve after crushing in the presence of PRP-1

A comparative morphological and histochemical study of the dynamics of de- and regenerative processes in the damaged sciatic nerve (SN) area was conducted in rats at different time points after crushing in the presence of proline-rich peptide (PRP-1). We measured the activity of Ca²⁺-dependent acid phosphatase (AP). At the fifth day after SN crushing on the site of injury, we observed changes in the directions of nerve fibers and disruption of their structure, in particular, swelling of Schwann hollow tubes. Later, we found proliferation of cells of the endoneurium and Schwann cells in the extensor bundle (N. peroneus communis), which promoted recovery of nerve fibers and was accompanied by appearance of the maximum activity AP. We also showed partial recovery of the flexor bundle (N. Gastrocnemius). At 17 days after the trauma, as a result of successful regeneration of the damaged nerve, we observed the recovery of nerve fibers and their structures, which confirms the neuroprotective characteristics of PRP-1