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It was stated with model of bilateral photochemically induced thrombosis of the prefrontal cortex by injected intranasally or intraperitoneally in 1h after operation new derivatives of eritropoetine: Epo, Epo-Fc, Epo-Tr provoked neuroprotective and antiamnestic action. Epo-Fc demonstrated more effective action by intranasal injection.

Objective: The search of the structural and functional brain characteristics is one of the most studied directions in the modern biological psychiatry. However, in spite of the numerous studies the results are still controversial. As the necessity of the shift of the current paradigm in schizophrenia research evolves it has been suggested to discriminate not only abnormal but stable functioning neuronal circuits as well. Consequently, the aim is formulated as the search of the minimal brain damage sufficient for disease development., Material and Methods: Author analyzed the auditory oddball P300 latency (as a marker of information processing speed), N-acetylaspartate level in the dorsolateral prefrontal cortex (as a marker of neuronal integrity in this brain area) and fractional anisotropy of the fasciculus uncindtus which connects the frontal and temporal lobes (as a marker of white matter bundles microstructure) in 30 patients with schizophrenia and 27 healthy people., Results and Conclusion: The findings showed that all the tested characteristics are not "obligatory" for schizophrenia.

According to the Neurodevelopmental hypothesis, the long-lasting cognitive deficit in schizophrenia and other types of neuropathology may occur by injurious factors, such as hypoxia, traumas, infections that take place during pre- and postnatal development, at least at early stages. These pathological conditions are often associated with the high production of pro-inflammatory cytokine interleukin-1B (IL-1B) by the cells of immune and nervous systems. We investigated the expression of genes involved in the neuroplastic regulation (Fgf2 and Timp2) in medial prefrontal cortex and dorsal and ventral regions of hippocampus of adult rats that were treated with IL-1beta between P15 and P21. The learning impairment in IL-1beta-treated rats is accompanied by lower FGF-2 mRNA levels in medial prefrontal cortex and ventral (not dorsal) hippocampus, but TIMP-1 was not affected. No differences in TIMP-1 and FGF-2 mRNA expressions were observed in untrained IL-1beta-treated when compared to control rats.

Using immunohistochemical method, it was demonstrated that neurons of the cerebral cortex have the capacity to express hypoxia-inducible factor-1 alpha (HIF-1α) in normoxia. Intensity of this process is different for rats having unequal tolerance to hypoxia. Basal HIF-1α expression in neurons of rats with low-resistance (LR) to hypoxia is higher compared to rats with high-resistance (HR). Bilateral photochemically induced focal ischemic insult in the rat prefrontal cortex completely suppressed HIF-1α neuronal expression the in the ischemic zone and only partially--in the area of the penumbra. Neuronal injury was more pronounced in cortex of LR rats compared to HR rats. These findings suggest that functional significance of HIF-1α is greater in neurons of the cerebral cortex of LR rats compared to HR rats.

The neuroprotective effects of dipeptide GK-2h, a mimetic of nerve growth factor, in bifocal photoinduced ischemia in rat brain prefrontal cortex was studied. It was shown that GK-2h, injected intraperitonealy in dose 0.1 mg/kg in 1 h or 4 h after operation and then on 2nd, 4th and 8th days, prevented significantly on 9th day from increasing volume of cortical infarction.

On the model of acute ischemic damage of prefrontal areas of the rats brain cortex was shown, that intranasal injection of glutamate antibodies over one hour after ischemic damage of brain prefrontal areas leads to diminishing of glutamate content in hippocampus and prefrontal cortex.

Some structural and functional characteristics of the dorsolateral prefrontal cortex and corpus callosum genu were analyzed in comparison with electrophysiological markers of selective attention in 18 mentally healthy subjects and 22 remitted patients with juvenile schizophrenia. In both topography zones there were no statistically significant intergroup differences in N-acetylaspartate and choline compounds (by proton MR-spectroscopy), whereas fractional anisotropy (by diffusion tensor imaging) in the corpus callosum genu was lower in patients. Absence of significant correlations between the imaging characteristics and psychopathology scores and their weak correlations with P300 suggest a poor involvement of the analyzed structures in the processes which determine cognitive disorders in patients with juvenile schizophrenia.

It was stated, that with bilateral photochemically induced thrombosis of the prefrontal cortex peptide semax and the AB-Glu by intranasal injection provoke pronounced neuroprotective and antiamnestic action. Intranasal injection semax (250 mkg/kg/daily during six postoperative days) and AB-Glu (250 mkg/kg in 1 hour after phototrombosis) demonstrate diminishing of cortex damage volume and relieve preservation and reproduction rat passive avoidance reflex, acquired before bilateral photochemically induced thrombosis of prefrontal cortex.

Neuroprotective and antiamnesic effects of human nerve growth factor (HNGF) synthetic dipeptide mimetic bis-(N-monosuccinyl-glycyl-lysine)hexamethylenediamide (GK-2h) has been studied on a model of bilateral photochemically induced focal ischemical brain injury in prefrontal cortex of rats. It is established that a single intraperitoneal injection of GK-2h (0.1 mg/kg) 1 h or 4 h after operation, followed by injections on the 2nd, 4th and 8th days after operation, results (on the 9th day) in reduction of the cortical infarction volume by 47 or 65%, and leads to restoration of the passive avoidance reflex (acquired before experimental ischemic insult) by 42 and 60%, respectively. It is concluded that GK-2h possesses significant neuroprotective properties.

Effects of 14-d suspension on the processes of rats' nervous cells conjugation in the brain cognitive cortex were studied. Signs of cognitive functions degradation and decrease of the number of conjugated nervous cells were found in the experimental group after suspension. This evidence are qualified as a negative effect of suspension on memory and physiological regeneration of neurons.

Perifocal ischemia zone ultrastructural changes caused by unilateral photoinduced thrombosis of the rat prefrontal brain and reciprocal changes in an opposite hemisphere of a brain in 1 and 24 hours after an ischemia are investigated. Reactive changes of microcirculation, astrocytes, neurons in the perifocal zone of the ischemia, and also in the contralateral site of the intact hemisphere as increase in hematoencephalic barrier permeability, numbers of degraded neurons, astrocyte transport injury and glucose metabolic imbalance are revealed. The degree of reactive changes of neurons and glia in the contralateral hemisphere is less expressed, than in a right hemisphere and has other temporal dynamics.

The effect of the new original drug celleks on the functional CNS activity and volume of ischemic damage has been studied in the experimental model of photochemically induced bilateral thrombosis of the prefrontal cortex. The chronic (once a day during 4 days) and even single (one hour after the operation) treatment of rats with celleks (intraperitoneal, 3 mg/kg) after the cortical photothrombosis resulted in the restoration of passive avoidance and diminishing of the volume of ischemic damage.

Photothrombosis of the vessels in the prefrontal areas of the rat cortex 20 days before learning leads to development of ischemic infarction in the exposed area with profound deficits in acquisition of the Morris water maze task: length of path and time of search of hidden-platform in water maze increased vs false-operated rats. It suggests prefrontal cortex involvement in spatial navigation.

A qualitative and quantitative electron microscopic study of oligodendroglial cells was performed in autoptic (4-6.5 hours after death) prefrontal area 10 in 16 cases of schizophrenia, 6 cases of bipolar affective disorder and 16 normal controls, as well as in the caudate nucleus in same schizophrenic and control cases. The signs of reactive, regressive, and progressive changes of oligodendroglia were described in endogenous psychoses. ANOVA demonstrated a significant decrease in the area of the nucleus, in the volume density of euchromatin, in the volume density and count of mitochondria in oligodendroglial cells in the caudate nucleus and prefrontal area. In affective psychosis, there was a significant reduction in the area of the nucleus and in the volume density of euchromatin and slight changes in cellular organelles. No correlation between the changes and the postmortem interval, age, and neuroleptic therapy, as well as the most pronounced changes in oligodendroglial cells in subgroups of continuous schizophrenia and those with predominantly negative symptoms suggest the involvement of abnormal oligodendroglial cells in the pathogenesis of endogenous psychoses.