[The effect of semax and its C-end peptide PGP on Vegfa gene expression in the rat brain during incomplete global ischemia].

Vascular endothelial growth factor (VEGFA) is a hypoxia-inducible signal glycoprotein. VEGFA causes vascular endothelial cell growth and proliferation, that leads to the regeneration of vascular network in brain regions damaged by ischemia. However, this protein is involved in processes of inflammation and edema in early stages of ischemia. Synthetic peptide semax shows neuroprotective and anti-inflammatory properties and is actively used in the treatment of ischemia.We have previously shown that semax reduces vascular injury and activates the mRNA synthesis of neurotrophins and their receptors under global cerebral ischemia in rats. Here we have analyzed the effects of semax and its C-terminal Pro-Gly-Pro tripeptide upon Vegfa mRNA expression in different rat brain regions after common carotid artery occlusion. The animals were decapitated 30 min, 1, 2, 4, 8, 12, 24 h after the operation. It was shown that ischemia increases levels of Vegfa mRNA in the rat brain of animals (4 h after the occlusion--in the cerebellum, cerebral cortex and hippocampus, 8 h--in the cortex and hippocampus, and 24 h in the cortex). Semax treatment reduces Vegfa mRNA levels in the frontal cortex (4, 8 and 12 h after the occlusion) and hippocampus of ischemic rats (2 and 4 h). Effect of PGP on the Vegfa gene expression was almost negligible. Our results showed that semax prevents activating effect ofhypoxia on the Vegfa gene expression in early stages of global ischemia. Furthermore, increase in the level of mRNA Vegfa in the hippocampus (24 h after occlusion) perhaps reflects neuroprotective properties of this drug.

[The effect of semax and its C-end peptide PGP on expression of the neurotrophins and their receptors in the rat brain during incomplete global ischemia].

Neurotrophins regulate key function of nervous tissue cells. Analysis of neurotrophins mRNA expression is an appropriate tool to assess therapeutic efficiency of the anti-stroke drugs. We have analyzed the effect of synthetic peptide semax and its C-terminal Pro-Gly-Pro tripeptide upon mRNAs expression of neurotrophins Ngf, Bdrf, Nt-3 and their receptors TrkA, TrkB, TrkC, p75 in rat frontal lobes, hippocampus and cerebellum after bilateral common carotid artery occlusion. The animals were decapitated 30 min, 1, 2, 4, 8, 12, 24 h after the operation. The mRNA expression of neurotrophins and their receptors was assessed by relative quantification using real-time RT-PCR. Our showed that ischemia causes a significant decrease in gene expression in the hippocampus. Semax and PGP affected the expression of neurotrophins and their receptors predominantly in the frontal cortex and hippocampus of the ischemized animals. In the frontal cortex, Semax treatment resulted in a decrease of mRNA level of receptors, while PGP treatment increased the level of these mRNA. Maximal neuroprotective effect of both peptides has been observed in the hippocampus 12 h after occlusion. A decrease of gene expression of neurotrophins and their receptors caused by the occlusion was overcome by Semax and PGP. These results clarify the semax mechanism of and present certain features of mRNA's expression of neurotrophins and their receptors in experimental conditions.

[The new MRI pulse sequence: experience in emergency neuroradiology].

The new pulse sequence (PS) has been obtained on MRI tomography Ellipse, B=0,15 and Biospec 70/30, B=7 T. The new pulse images of the brain combine features of FLAIR and its sensitivity to magnetic field heterogeneity. We named its PS as the T2 Fluid Attenuation Gradient Echo (T2 FLAGE). The T2 FLAGE characteristics of tissue contrast as well as its efficacy in detection of ICH have been assessed in 57 patients with acute stroke and in 16 experimental rats. The analysis of tissue contrast of lesions and normal brain structure has revealed the greater visibility of T2 FLAGE images compared to FLAIR. At the same time, the images sensitivity of magnetic field heterogeneity is retained. The ROC-analysis has shown that T2 FLAGE images are more effective in differential diagnosis of stroke type compared to FLAIR.

[The effect of cerebrolysin in dosage 50 ml on the volume of lesion in ischemic stroke].

The purpose of this randomized, double-blind, placebo-controlled study was to assess safety and efficacy of cerebrolysin used in dosage 50 ml in acute ischemic stroke. Forty-seven patients with ischemic stroke, aged 45-85 years, who were admitted to a clinical unit within the first 12 h after stroke onset were included in the study. A quantitative time-related MRI analysis of the dynamics of neurological deficit revealed the more rapid decrease of stroke volume to the 28th day in the group treated with cerebrolysin (45.4% versus 43.6% in the placebo-group (p < 0.05)). No side-effects of treatment with cerebrolysin was found. The results of this prospective, randomized, placebo-controlled study suggest the positive effect of cerebrolysin on the dynamics of volume lesion in patients with ischemic stroke.

[Comparative assessment of MR-semiotics of acutest intracerebral hematomas in low- and extra high-field frequency magnetic resonance tomography].

An objective of the study was to compare sensitivity of low- and extra high-field frequency magnetic resonance (MR) tomography of acutest intracerebral hematomas (ICH) and to assess differences between symptoms in obtained images. A study was conducted using experimental ICH in rats (n=6). Hematomas were formed by two injections of autologic blood into the brain. MR-devices "Bio Spec 70/30" with magnetic field strength of 7 T and "Ellipse-150" with magnetic field strength of 0,15 T were used in the study. MR-tomography was carried out 3-5 h after the injections. Both MR-devices revealed the presence of pathological lesion in all animals. Extra highfield frequency MR-tomography showed the specific signs of ICH caused by the paramagnetic effect of deoxyhemoglobin in T2 and T2*-weighted images (WI) and low frequency MR-tomography - in T2*-WI only. The comparable sensitivity of low- and extra high-field frequency MR-devices in acutest ICH was established.

[Experimental hemorrhagic stroke: the study of neuropeptides (MIF, selank) in the intraperitoneal injection].

The aim of this study was to examine Taftsin derivates--macrophage inhibitory factor (MIF, Thr-Lys-Pro) and heptapeptide selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) in the model of experimental intracerebral hemorrhage in rats. The double autologous blood injection in the basal nucleus was used as a model of intracerebral hemorrhage. Animals ware randomly divided into three groups--the control group (n = 5) was treated with saline, the second group (n = 5) was injected with MIF in dose 150 mkg/ kg/day, the third group (n = 5) received Selank in dose 300 mkg/kg/day. Intraperitoneal injection of peptides was used. Body weight assessment, neurological examination and brain MRI were performed in 24, 72 hours and 10 days after the hematoma formation. The effect of neuropeptides on the functional restoration in animals, in the absence of the effect on hematoma volume and perifocal edema, was found. The significant reduction of perifocal edema and hematoma volume was observed in the 10th day after the hematoma formation in all experimental groups (p < 0.05). Only the control group of animals showed the significant (p < 0.05) weight loss in the 3rd day after the operation. The rate of neurological deficit was different: the significant improvement assessed with Menzes and limb placing test scales was seen only in the groups treated with neuropeptides in the 10th day.

[MRI semiotics features of experimental acute intracerebral hematomas].

The aim of this study was to assess the possibility of revealing intracerebral hematomas (ICH), using MRI, within the first hours after onset and to determine their MRI semiotics features. Thirty animals with experimental ICH were studied. A method of two-stage introduction of autologous blood was used to develop ICH as human spontaneous intracranial hematomas. Within 3-5h after blood introduction to the rat brain. The control MRI was performed in the 3rd and 7th days after blood injections. ICH were definitely identified in the first MRI scans. The MRI semiotics features of acute ICH and their transformations were assessed. The high sensitivity of MRI to ICH as well as the uniform manifestations in all animals were shown. In conclusion, the method has high specificity for acute ICH detection.

The effects of hormones of the hypothalamo-hypophyseal-adrenal, renin-angiotensin, and thyroid hormone systems on the formation of dyscirculatory encephalopathy.

Measurements were made of plasma levels of free (f) thyroxine (fT4), triiodothyronine (fT3), thyrotropic hormone (TSH), adrenocorticotrophic hormone (ACTH), aldosterone, and renin in patients with dyscirculatory encephalopathy (DE). Their influences on the development of chronic circulatory insufficiency were assessed. A total of 39 patients were studied (aged 45-73 years) with DE stages I and II, without acute or chronic (in the exacerbation phase) somatic illness. These observations showed that diffuse lesions of brain tissues of different severities were accompanied by the following changes in thyroid homeostasis: 1) significant combined increases in TSH without alteration to the "fT3-TSH" negative feedback regulatory mechanism in patients with stage I DE; 2) significant combined decreases in TSH levels with marked suppression of the conversion of thyroxine into triiodothyronine and an interaction with impairments in the "fT3-hypophysis" system in patients with stage II DE. In addition, there were changes (increases) in cortisol levels with simultaneous decreases in renin levels in patients with stage II DE as compared with patients with stage I DE. Correlation analysis demonstrated the absence of any relationship between the age of the patients, the state of hormonal homeostasis, and the extent of vascular stenosis. These results suggest a role for hormones of the hypothalamo-hypophyseal-adrenal, thyroid, and renin-angiotensin systems in the mechanism by which DE develops as well as the possibility of using tests for these hormones as additional criteria for assessing the severity of diffuse brain lesions.

[The influence of the hormones of hypothalamo-pituitary-adrenal, renin-angiotensin, and thyroid hormonal systems on formation of vascular encephalopathy]. / Vliianie gormonov gipotalamo-gipofizarno-nadpochechnokovoi, renin-angiotenzinovoi i tireoidnoi sistem na formirovanie distsirkuliatornoi éntsefalopatii.

The aim of the study was to investigate the concentration changes of free (f) thyroxine (fT4), triiodothyronine (fT3), thyrotrophic hormone (TTH), adrenocorticotrophic hormone (ACTH), aldosterone and renin in the blood plasma of patients with vascular encephalopathy (VE) and to evaluate their influence on formation of chronic blood circulation deficiency. Thirty-nine patients with VE of stages I and II, aged 45-73 years, without current acute or chronic (in exacerbation stage) other somatic diseases have been studied. The results revealed that a different extent of diffuse lesion of brain tissue was accompanied by an own pattern of thyroid homeostasis: 1) significantly higher TTH levels with intact regulatory negative feedback "fT3-TTH" in patients with VE, stage 1; 2) significant TTH concentration decrease, with pronounced suppression of thyroxine conversion to triiodothyronine and interaction disturbance in the "fT3--pituitary gland" system, in patients with VE in stage II. A distinct trend towards plasma cortisol level increase as well as significantly lower active plasma renin levels were found in the patients with VE in stage II comparing to those in stage I. Correlation analysis demonstrated the absence of an interaction between patient's age and hormonal homeostasis state and an extent of vascular stenosis. The data suggest involvement of the hormones of hypothalamopituitary-adrenal, thyroid and renin-angiotensin systems in VE formation thus enabling using of the results of their testing as an additional criterion for estimation of brain diffusive lesion severity.