ABSTRACT
The dynamics of the balance of indices of pro- and p53- Bcl-2 anti-apoptotic processes in the hippocampus of rats with experimental diabetes mellitus (DM) complicated by incomplete global cerebral ischemia-reperfusion was investigated. It is shown that p53 proapoptotic processes in animals without diabetes after 20 minutes of ischemia/l hour reperfusion in all fields of the hippocampus are activated in the background of increasing Bcl-2 antiapoptotic processes in the fields CAl, CA2, CA4 and depression of it - in the CA3 field. In the early postischemic period in rats with DM activity of the p53-proapoptotic processes in fields CAl, CA3, CA4 significantly exceeds that in non-diabetic rats (area of p53- IRM increases on 110, 60 and 27 %), and was significantly lower than that detected in CA2 field. On the 12th day of post-ischemic period, activation of apoptosis in field CAl occurs in the background of inert antiapoptotic processes, in animals without diabetes, as well as in diabetic rats, but the indicators characterizing of apoptotic activity in rats with diabetes were higher (specific contents of p53 protein and area ofp53 -IRM increases on 38 and 43 %). During this period, in the CA2 region of the non-diabetic animals, some depression of the antiapoptotic processes with a slight predominance of proapoptotic processes was detected. In the field of CA3 region of rats without diabetes, the retention of activity of proapoptotic processes and the deepening in the dynamics of depression of antiapoptotic processes were showed. In rats with DM, the oppression of both mechanisms with a significant depression of antiapoptotic processes was observed. On the 12th day of experiment in the field CA4, the most balanced relationship were detected between the studied of the processes due to their parallel and unidirectional changes both in the rats without diabetes as well as with DM. The results point on the modifying effect ofDM on susceptibility ofhippocampal fields to ischemic-reperfusion injury.
Subject(s)
Apoptosis , Brain Ischemia/metabolism , Diabetes Mellitus, Experimental/metabolism , Hippocampus/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Reperfusion Injury/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Brain Ischemia/pathology , Diabetes Mellitus, Experimental/pathology , Hippocampus/pathology , Male , Rats , Reperfusion Injury/pathologyABSTRACT
The effect of diabetes mellitus on the dynamics of neurocyte and gliacyte apoptosis intensity in the cortex of the frontal, parietal and temporal lobes of the cerebral hemispheres under conditions of ischemic-reperfusion lesion has been studied in experiments on rats. The level of apoptotic processes in the neuro- and gliacytes of the frontal cortex has been found to be unchanged after 20 minutes of carotid ischemia followed by one hour reperfusion according to the indices examined in animals with out diabetes mellitus. Apoptosis of neurocytes is activated in the cortex of the parietal lobe, and that of the neuro- and gliacytes in the cortex of the temporal lobe. Three-month diabetes mellitus intensifies apoptosis of neurons and glial cells in the cortex of the frontal and temporal lobes, neurons in the cortex of the parietal lobe and decreases apoptosis of gliacytes in it. In early ischemic-reperfusion period the activity of apoptotic processes in the cortex of the frontal and temporal lobes does not change in animals with diabetes mellitus, but it decreases in the cortex of the parietal lobe at the expense of glial cells. On the 12th day of observation the activity of apoptotic processes in neurocytes of the cortex of the temporal lobe increases in rats without diabetes mellitus, and it decreases in the glial cells. We detected a reduced content of the protein p53 in neurons and increased density of Ñ53+-cells. In this period of observation in rats with diabetes mellitus the activity of apoptotic processes decreases in general both in neurons and glial cells of all the lobes. The results obtained point for the availability of regional differences in the dynamics of reaction of the cerebral hemisphere lobes in response to ischemic-reperfusion injury charachterized by the intensity of apoptosis of neurons and glial cells. The results also point for modifying effect of diabetes mellitus on the indices studied.