RESUMEN
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.
Asunto(s)
Benzofenonas , Craneotomía , Polietilenglicoles , Polímeros , Cráneo , Polímeros/química , Animales , Cráneo/cirugía , Cráneo/lesiones , Cráneo/diagnóstico por imagen , Polietilenglicoles/química , Craneotomía/métodos , Ratas , Masculino , Procedimientos de Cirugía Plástica/métodos , Cetonas/química , Materiales Biocompatibles/química , Encéfalo/cirugía , Ratas WistarRESUMEN
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.
Asunto(s)
Lesiones Traumáticas del Encéfalo/patología , Lesiones Encefálicas/patología , Animales , Modelos Animales de Enfermedad , Masculino , RatasRESUMEN
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. The neuroprotective (MRI) and antiamnestic (PA) effects of mutant molecules of erythropoietin derivatives are shown.
Asunto(s)
Eritropoyetina , Trombosis Intracraneal , Mutación , Fármacos Neuroprotectores/farmacología , Corteza Prefrontal , Animales , Modelos Animales de Enfermedad , Eritropoyetina/genética , Eritropoyetina/farmacología , Trombosis Intracraneal/inducido químicamente , Trombosis Intracraneal/tratamiento farmacológico , Trombosis Intracraneal/fisiopatología , Masculino , Corteza Prefrontal/metabolismo , Corteza Prefrontal/fisiopatología , RatasRESUMEN
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 ÐPO-TR exhibited prolonged neuroprotective properties.
Asunto(s)
Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Eritropoyetina/química , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Animales , Humanos , Masculino , Fármacos Neuroprotectores/uso terapéutico , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Ratas , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
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.
Asunto(s)
Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/fisiopatología , Modelos Biológicos , Animales , Lesiones Encefálicas/patología , HumanosRESUMEN
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.
Asunto(s)
Eritropoyetina/farmacología , Trombosis Intracraneal/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Corteza Prefrontal/metabolismo , Animales , Trombosis Intracraneal/metabolismo , Trombosis Intracraneal/patología , Masculino , Corteza Prefrontal/patología , RatasRESUMEN
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.
Asunto(s)
Anticuerpos/farmacología , Isquemia Encefálica/metabolismo , Dopamina/metabolismo , Ácido Glutámico/inmunología , Corteza Prefrontal/metabolismo , Serotonina/metabolismo , Animales , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Corteza Prefrontal/efectos de los fármacos , RatasRESUMEN
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.
Asunto(s)
Isquemia Encefálica/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hipoxia/metabolismo , Neocórtex/metabolismo , Corteza Prefrontal/metabolismo , Accidente Cerebrovascular/metabolismo , Animales , Hipoxia/fisiopatología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neocórtex/patología , Neuronas/metabolismo , Especificidad de Órganos , Corteza Prefrontal/patología , RatasRESUMEN
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.
Asunto(s)
Anticuerpos/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Ácido Glutámico/inmunología , Corteza Prefrontal/patología , Animales , Anticuerpos/inmunología , Ácido Glutámico/análisis , Hipocampo/química , Hipocampo/patología , Masculino , Corteza Prefrontal/química , RatasRESUMEN
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.
Asunto(s)
Aminoácidos/metabolismo , Anticuerpos/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Ácido Glutámico/inmunología , Neurotransmisores/metabolismo , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/patología , Animales , Anticuerpos/inmunología , Encéfalo/patología , Trombosis Intracraneal/tratamiento farmacológico , Masculino , Corteza Prefrontal/metabolismo , RatasRESUMEN
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.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Dipéptidos/farmacología , Factor de Crecimiento Nervioso/farmacología , Fármacos Neuroprotectores/farmacología , Peptidomiméticos/farmacología , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Reacción de Prevención/efectos de los fármacos , Isquemia Encefálica/patología , Isquemia Encefálica/fisiopatología , Dipéptidos/química , Humanos , Masculino , Factor de Crecimiento Nervioso/química , Fármacos Neuroprotectores/química , Peptidomiméticos/química , Corteza Prefrontal/patología , Corteza Prefrontal/fisiopatología , Ratas , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/fisiopatologíaRESUMEN
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.
Asunto(s)
Hormona Adrenocorticotrópica/análogos & derivados , Anticuerpos/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Ácido Glutámico/inmunología , Fármacos Neuroprotectores/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Corteza Prefrontal/patología , Administración Intranasal , Hormona Adrenocorticotrópica/administración & dosificación , Hormona Adrenocorticotrópica/uso terapéutico , Amnesia/etiología , Amnesia/inmunología , Amnesia/prevención & control , Animales , Anticuerpos/administración & dosificación , Anticuerpos/sangre , Isquemia Encefálica/complicaciones , Isquemia Encefálica/inmunología , Isquemia Encefálica/patología , Modelos Animales de Enfermedad , Masculino , Fármacos Neuroprotectores/administración & dosificación , Fragmentos de Péptidos/administración & dosificación , Corteza Prefrontal/efectos de los fármacos , Ratas , Resultado del Tratamiento , gammaglobulinas/administración & dosificación , gammaglobulinas/uso terapéuticoRESUMEN
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.
Asunto(s)
Reacción de Prevención , Isquemia Encefálica , Corteza Cerebral , Hipocinesia , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Isquemia Encefálica/fisiopatología , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Hipocinesia/metabolismo , Hipocinesia/patología , Hipocinesia/fisiopatología , Masculino , RatasRESUMEN
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.
Asunto(s)
Infarto Encefálico/tratamiento farmacológico , Dipéptidos/farmacología , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Factor de Crecimiento Nervioso/metabolismo , Animales , Encéfalo/patología , Encéfalo/cirugía , Infarto Encefálico/patología , Infarto Encefálico/cirugía , Corteza Cerebral/metabolismo , Dipéptidos/administración & dosificación , Dipéptidos/toxicidad , Masculino , Fármacos Neuroprotectores/farmacología , Péptidos/farmacología , RatasRESUMEN
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.
Asunto(s)
Fusión Celular , Cognición/fisiología , Hipocinesia , Memoria/fisiología , Neuronas , Corteza Prefrontal/patología , Simulación del Espacio , Animales , Reacción de Prevención , Benzoxazinas , Suspensión Trasera/métodos , Hipocinesia/patología , Hipocinesia/fisiopatología , Hipocinesia/psicología , Masculino , Microscopía Electrónica , Microtomía , Modelos Animales , Regeneración Nerviosa/fisiología , Neuronas/citología , Neuronas/ultraestructura , Oxazinas/análisis , Corteza Prefrontal/fisiopatología , Ratas , IngravidezRESUMEN
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.
Asunto(s)
Anticuerpos/farmacología , Reacción de Prevención/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Ácido Glutámico/inmunología , Corteza Prefrontal/fisiopatología , Animales , Anticuerpos/administración & dosificación , Reacción de Prevención/fisiología , Ensayo de Inmunoadsorción Enzimática , Masculino , Fotoquímica/métodos , Ratas , Rosa Bengala , Estadísticas no ParamétricasRESUMEN
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.
Asunto(s)
Barrera Hematoencefálica/ultraestructura , Isquemia Encefálica/patología , Trombosis Intracraneal/patología , Neuroglía/ultraestructura , Neuronas/ultraestructura , Corteza Prefrontal/patología , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/fisiopatología , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatología , Trombosis Intracraneal/metabolismo , Trombosis Intracraneal/fisiopatología , Masculino , Neuroglía/metabolismo , Neuronas/metabolismo , Corteza Prefrontal/metabolismo , Corteza Prefrontal/fisiopatología , Ratas , Factores de TiempoRESUMEN
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. Mexidol-dependent overexpression of subunits of mitochondrial enzymes and PGC-1α is observed only with the course of the drug. CONCLUSION: The results indicate the ability of mexidol to induce cerebral mitochondriogenesis and eliminate mitochondrial dysfunction in young and aging animals and, thus, exert an effect on one of the key pathogenetic links of the development of disorders in aging and neurodegenerative diseases.
Asunto(s)
Envejecimiento/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Enfermedades Neurodegenerativas/tratamiento farmacológico , Picolinas/farmacología , Factores de Edad , Envejecimiento/patología , Animales , Masculino , Mitocondrias/enzimología , Mitocondrias/patología , Enfermedades Neurodegenerativas/enzimología , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Picolinas/administración & dosificación , Ratas , Receptores Acoplados a Proteínas G/biosíntesis , Factores de Transcripción/biosíntesisRESUMEN
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. Normalization of the dikaryon and mononuclear cell structure was observed after 56 days. Presumably, cell fusion promotes their morphological restoration and regeneration of the lost functional capacity. Fusion is regarded as a manifestation of physiological and reparative regeneration of the cortex.
Asunto(s)
Isquemia Encefálica/patología , Fusión Celular , Corteza Cerebral , Neuronas , Regeneración/fisiología , Accidente Cerebrovascular/patología , Animales , Corteza Cerebral/citología , Corteza Cerebral/patología , Corteza Cerebral/fisiología , Humanos , Masculino , Neuronas/metabolismo , Neuronas/ultraestructura , RatasRESUMEN
It was shown, that photochemically induced thrombosis of blood vessels in prefrontal areas of the cortex lead to the formation of well-defined infarct zone. Bilateral prefrontal cortex injury impair acquisition of the Morris water-maze on postoperative days 20-24. Chronic treatment of brain-injuried rats with peptide semax, a synthetic analogue of ACTH(4-7), at a dose of 250 microg/kg (intranasal, once a day) during six days after photothrombosis resulted in restoration of spatial learning ability. The observed long-lasting antiamnesic effects of the semax are probably caused by its strong neuroprotective action, and ability to induce synthesis of nerotrophic factors.