The variable adaptive response of human basal ganglia neurons to ischemic injury

Arterial hypertension is a socially significant disease, one of whose complications is cerebral ischemia. Various mechanisms are involved in the adaptation of neurons to hypoxia, including those modulating mitochondrial activity, the autophagy system, and the regulation of apoptosis. Objective. To study the immunohistochemical features of markers of autophagy, mitochondrial dynamics and regulation of apoptosis in neurons during chronic diffuse and focal ischemia in grade II-III hypertension in the region of the basal ganglia (BG) of humans. Material and methods. The brain of deceased patients with grade II—III hypertension with and without lacunar infarcts (LI) in the area of the BG, and control cases with the absence of hypertension, was studied. Immunohistochemical analysis of the proteins Drp-1, Opa-1, Mfn-2, Beclin-1, SQSTM-1, and Bcl-2 was performed, followed by determination of their staining intensity in three zones at different distances from the LI center. Results. The LI zones were characterized by varying changes in the studied markers. Peri-infarction zones 1 and 2, closest to the LI center, were characterized by increased levels of the markers Bcl-2, Beclin-1, SQSTM1, Opa-1, and Mfn-2 compared to control cases. In the zone furthest from the infarction center, a decrease in the SQSTM-1 marker and an increase in the Drp-1 marker were observed compared to other LI zones. In cases of hypertension without the development of LI, an increase in the Beclin-1 level and an increase in the Opa-1 level were observed compared to control cases. Conclusion. The degree of ischemic damage can determine the pattern of the neuron’s adaptive response: in areas with the most severe ischemic damage, the Bcl-2-mediated mechanism of protection from apoptosis is activated and the balance of mitochondrial dynamics shifts towards the predominance of the fusion of these organelles. With a relatively low severity of ischemia, a shift in the balance of mitochondrial dynamics towards the division of these organelles was found; in the case of moderate severity of ischemic damage, activation of both division and fusion of mitochondria is observed.