Experimental Modeling of Cranial Injury and Defect Reconstruction Using Superconstructive Polymers (PEEK).

Experimental model of resection craniotomy with subsequent reconstruction of the defect with a polymer implant enables comprehensive assessment of functional and ultrastructural changes during replacement of the damaged tissue. Reconstruction of a skull defect was accompanied by transient motor disturbance in the acute period and did not cause functional disorders and neurological deficits in a delayed period. Histological examination of osteal and brain tissue revealed no pathological reactions that could be associated with the response to the chemical components of the implant.

Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis.

The pharmacological induction and activation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), a key regulator of ischemic brain tolerance, is a promising direction in neuroprotective therapy. Pharmacological agents with known abilities to modulate cerebral PGC-1α are scarce. This study focused on the potential PGC-1α-modulating activity of Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) and Semax (ACTH analog) in a rat model of photochemical-induced thrombosis (PT) in the prefrontal cortex.

[The effect of Mexidol on cerebral mitochondriogenesis at a young age and during aging].

Aim: To study the ability of mexidol to induce cerebral mitochondriogenesis in the brain of young and aging rats.

Material And Methods: Expression level of marker proteins of cerebral mitochondriogenesis was evaluated during treatment with mexidol (20, 40, 100 mg/kg; 20 days; intraperitoneally) in the cerebral cortex of young (3 month) and aging (6, 9, 12, and 15 month) outbred male rats, using the Western blot analysis.

Results: It has been shown for the first time that the course injections of mexidol in doses of 40 and 100 mg/kg is accompanied by dose-dependent induction of the succinate receptor SUCNR1 and protein markers of mitochondrial biogenesis: transcription coactivator PGC-1α, transcription factors (NRF1, TFAM), catalytic subunits of respiratory enzymes (NDUV2, NDUV2,cytb, COX2) and ATP synthase (ATP5A) in the cerebral cortex of young and aging outbred male rats.

Neuroprotective and antiamnestic effects of mutant molecules of erythropoietin on model of photochemical thrombosis of rat brain prefrontal cortex.

Mutant EPO molecules, deprived of erythropoietic activity, but possessing cytoprotective action, were created by the method of genetic engineering. The assessment of the therapeutic effectiveness of the received mutant proteins was carried out by the retention of the conditioned reflex of passive avoidance (PA), developed before the ischemic injury of rat brain prefrontal cortex, and by the MRI-analysis of ischemic damage volume. Antiamnestic and neuroprotective action of mutant molecules - MERO-Fc and MEPO-TR is investigated on model of photothrombosis of rat brain prefrontal cortex at single intranasal introduction in 1 h after cortex ischemic damage.

Relationship between Morphofunctional Changes in Open Traumatic Brain Injury and the Severity of Brain Damage in Rats.

A correlation between the severity of morphofunctional disturbances and the volume of brain tissue injury determined by MRT was demonstrated on the model of open traumatic brain injury in rats. A relationship between the studied parameters (limb placing and beam walking tests and histological changes) and impact force (the height of load fell onto exposed brain surface) was revealed.

[Comparison of neuroprotective effects of derivatives of eritropoetine by different way of bringing in drugs with model of bilateral photochemically induced thrombosis of the prefrontal cortex of rat brain].

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.

[Modeling of traumatic brain injury].

Contemporary approaches to experimental traumatic brain injury modeling, the principles of functioning and techinical characteristics of appropriate equipment are reviewed. The methods describing traumatic brain injury modeling and assessment of brain structural and functional changes caused by the weight drop method are given.

Neuroprotective and antiamnesic effect of erythropoietin derivatives after experimental ischemic injury of cerebral cortex.

Using the model of bilateral photothrombosis of the blood vessels in the prefrontal cortex we have shown that new hybrid proteins derived from recombinant human erythropoietin, carbamylated EPO-Fc and EPO-TR fusion proteins, injected intraperitoneally 1 h after ischemic injury contribute to restoration of passive avoidance response formed before photothrombotic injury and reduction in the volume of the ischemic focus. These data attest to nootropic and neuroprotective activities of these hybrid proteins. Carbamylated glycopeptide derivative ЕPO-TR exhibited prolonged neuroprotective properties.

[Urgent changes in the expression of hypoxia-inducible factor-1α (HIF-1α) in the neocortex of rats with different tolerance to acute hypoxia underwent focal ischemic stroke prefrontal cortex].

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).

[The influence of glutamate antibodies on the level of neurotransmitter monoamines in brain structures of rats with ischemic damage of prefrontal cortex].

Experiments on the model of bilateral photothrombosis in prefrontal cortex showed that antibodies to glutamate one-time administered intranasally 1h after ischemic damage to the brain cortex lead to decrease of neurodegenerative influence of excitatory neurotransmitter after photothrombosis. It was showed the change of the level of dopamine, serotonin and their metabolites in hippocampus and prefrontal cortex.

[The saving role of glutamate antibodies with the acute ischemic damage of the rat brain prefrontal cortex].

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.

[Neuroprotective and antiamnesic effects of GK-2h dipeptide HNGF mimetic on a model of experimental ischemic stroke of brain cortex prefrontal areas].

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.

[The comparison of neuroprotective action of antibodies to glutamate and drug preparation semax in the focal ischemic damage of the brain prefrontal cortex of rats].

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.

Effect of antibodies to glutamate on the content of neurotransmitter amino acids in brain structures of rats with ischemic damage to the prefrontal cortex.

Experiments on the model of bilateral photothrombosis in the prefrontal cortex showed that antibodies to glutamate administered intranasally 1 h after ischemic damage to the brain cortex led to a decrease in glutamate content in the hippocampus and prefrontal cortex and had no effect on aspartate concentration in these structures of the brain.

[Morphofunctional study of antiortostatic hipokinesia action in the case of focal ischemic brain cortex damage].

It was investigated the influence of antiortostatic hipokinesia (ANOC) with different combinations with photothrombosis of prefrontal cortex of rat brain by quantitative measures of passive avoidance reflex and reparative processes on the creation of dikaryons in cortex. Recieved data let to suppose, that ANOC increase ischemic damages and decrease quantity of dikaryons in cortex.

Neuroprotective and antiamnestic effect of nerve growth factor dipeptide mimetic GK-2 in experimental ischemic infarction of brain cortex.

The neuroprotective and antiamnestic effects of GK-2 dipeptide (nerve growth factor mimetic) were studied on rats with photoinduced bilateral focal ischemia of the prefrontal cortex. Intraperitoneal injection of GK-2 in a dose of 1 mg/kg on days 1, 2, 4, and 6 postoperation led to a 62% reduction of cortical infarction volume on day 9 and completely preserved conditioned passive avoidance response trained before stroke.

[Structural and functional features of the rats' prefrontal cortex following 14-day suspension].

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.

[Contralateral ultrastructural changes of the perifocal zone of the local ischemia caused by photoinduced thrombosis of the rat prefrontal brain cortex].

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.

Effect of antibodies to glutamate on retention of conditioned passive avoidance response in rats with ischemic injury of the prefrontal cortex.

Experiments were performed on rats with bilateral photothrombosis of vessels in the prefrontal cortex. Intranasal administration of antibodies to glutamate (1 h after ischemia of the brain cortex) improved retention of conditioned passive avoidance response, which was elicited before ischemic damage. The content of antibodies to glutamate in the serum of rats increased significantly on day 8 after bilateral photochemical thrombosis of vessels in the prefrontal cortex compared to that in the control.

The role of cell fusion in physiological and reparative regeneration of the cerebral cortex.

The prefrontal (cognitive) cerebral cortex of rats was studied by morphological and physiological methods 56 days after stroke induced by photothrombosis. The cognitive capacity impaired after the intervention was completely restored by this time. The count of fused cells (dikaryons) increased significantly in experimental and sham-operated (control) animals in comparison with the early period (7 days) after surgery.

[Effect of celleks on functional and morphological changes in experimental focal ischemia of prefrontal areas of the rat brain cortex].

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.

Formation of spatial memory in rats with ischemic lesions to the prefrontal cortex; effects of a synthetic analog of ACTH(4-7).

Photochemically induced thrombosis of blood vessels in the prefrontal cortex in rats was shown to lead to ischemic infarcts in the lesion zone. Bilateral ischemic lesioning of the prefrontal cortex degraded measures of spatial memory when animals were tested in a Morris water maze with an invisible platform 20-24 days after surgery. Chronic intranasal administration of the peptide Met-Glu-His-Phe-Pro-Gly-Pro (Semax), a synthetic analog of ACTH(4-7), at a dose of 250 microg/kg/day during the first six days after photothrombosis, led to recovery of the animals' learning ability.

Heterokaryon formation as a method for neuron regeneration in postischemic injury to cerebral cortex in rats.

Rat prefrontal cortex was examined by light and electron microscopy after stroke induced by photothrombosis. An appreciable number of binuclear neurons with morphologically similar and different nuclei was detected in the perifocal zone and adjacent intact tissue. The satellite oligodendrocyte nucleus was frequently the second nucleus in binuclear neuron.

[Characteristics of learning in Morris water maze in rats with ischemic injury of prefrontal areas of the cortex].

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.

Neuroprotective effect of afobazole on rats with bilateral local photothrombosis of vessels in the prefrontal cortex.

We studied the neuroprotective effect of a new selective anxiolytic afobazole on rats with bilateral focal ischemic stroke in the prefrontal cortex caused by photothrombosis. Intraperitoneal injection of 5 mg/kg afobazole 1 h after surgery and over the next 8 days (daily treatment) produced a neuroprotective effect. Afobazole was far superior to the reference cerebroprotective drug cavinton (4 mg/kg) by neuroprotective activity.