PLEIOTROPIC ENZYMES OF APOPTOSIS AND SYNAPTIC PLASTICITY IN ALBINO RAT HIPPOCAMPUS AFTER OCCLUSION OF COMMON CAROTID ARTERIES

Aim: the aim of the study was to investigate the pleiotropic properties of the apoptotic enzyme caspase-3 and its associations with the synaptic plasticity of the hippocampus of albino rats in healthy animals and in rats after 20-min occlusion of the common carotid arteries.
Material and Methods. Total numerical density of neurons, ultrastructure of synapses, and area of immunohistochemically positive hippocampal synaptic terminals of CA1 stratum radiatum and stratum lucidum CA3 were studied by the methods of optical microscopy (hematoxylin and eosin stain), electron microscopy (uranyl acetate and lead citrate as contrast agents), immunohistochemistry (MAP2, synaptophysin, caspase-3, p53, and bcl-2), and morphometry in the brains of intact rats (n=5) and in animals after acute ischemia at day 1 (n=5), 3 (n=5), 7 (n=5), 14 (n=5), and 30 (n=25).
Results and Discussion. The study showed that 33.0% of pyramidal neurons in CA1 region and 17.4% of those in CA3 region underwent irreversible damage within 30 days of the post-ischemic period. Among the irreversibly damaged neurons, the cells with signs of coagulative-ischemic necrosis prevailed. In animals subject to ischemia, the relative area of synaptophysin-positive material initially decreased (at day 1) and then recovered (at days 3, 7). We found that caspase-3 colocalized with synaptophysin, which was especially evident in the giant synapses of the stratum lucidum of the hippocampal CA3 region. In the neurosomes of the hippocampal pyramidal cells, caspase-3 was not detected. However, this enzyme was found in the terminals of the axo-dendritic, axo-spine, and axo-somatic synapses. In the course of th e post-ischemic period, the most pronounced changes in the expression of caspase-3 were observed in the stratum radiatum of the CA1 field. Apoptosis regulatory proteins (p53, bcl-2) were detected in the individual neurons. In this regard, caspase-3 should be viewed in the context of its pleiotropy and involvement in the adaptation and recovery processes due to post-ischemic activation of neuroplasticity at the level of axons and synapses.
Conclusion. After acute ischemia caused by 20-min occlusion of the common carotid arteries, the activation of caspase-3 contributes to ischemic preconditioning and neuroprotection.

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