RESUMEN
The immunolocalization of apoptotic factors in rat neocortex was studied on the model of permanent occlusion of the middle cerebral artery with administration of exogenous BDNF. We revealed heterogeneous distribution of pro- and anti-apoptotic factors in the stroke area and in the surrounding penumbra, where caspase-3+ and p53+ cells were found. Their number was maximum on day 3 of ischemia. The number of neurons containing anti-apoptotic factors was relatively decreased. Injection of BDNF changed the distribution of apoptotic factors. In the penumbra area, BDNF enhanced the expression of Mdm2 primarily in the pyramid cells of layers V/VI and Bcl-2 in interneurons of layers II and III. Localization of p53 and caspase-3 varied at different terms of the ischemic period and showed an inverse dependence. Considering the selective neuroprotective effect of BDNF, various mechanisms of the formation of ischemic tolerance in neurons are proposed.
Asunto(s)
Isquemia Encefálica/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/metabolismo , Animales , Apoptosis/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Caspasa 3/metabolismo , Masculino , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Ratas , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Literature data and own experience in the studies of experimental stroke methodology are reviewed. Advantages and disadvantages of the common models of focal ischemia used in the laboratory practice are discussed in details. The advantages of the filament occlusion of the middle cerebral artery in rats as the most adequate model of human stroke are substantiated. The authors suggest a modification of this variant using an additional coagulation of the pterygopalatine artery that allows the exclusion of the retrograde and collateral blood flow into the inner carotid artery after ligation of the common and external carotid arteries.
