Edema-Swelling as a Standard Dose-Dependent Response of the Dentate Gyrus of the Hippocampal Formation to Acute Ischemia

Abstract

The aim of research was to study structural changes and give a morphometric characteristic of the edemaswelling manifestations of the dentate gyrus (DG) of the hippocampal formation in sexually mature white rats after common carotid artery occlusion (OCCA) of different duration and ligation (LCCA) of the common carotid arteries.Material and methods. Acute ischemia was simulated in white adult Wistar rats by 20-, 30-, and 40-min occlusion and ligation of the common carotid arteries. Histological (staining with hematoxylin-eosin, according to Nissl), immunohistochemical (NSE, MAP-2, GFAP) and morphometric research techniques were used for morphological investigations. Morphometric analysis of the edema-swelling manifestations was carried out on samples stained with hematoxylin-eosin using plugins of the ImageJ 1.53 program (Find Maxima, Find Foci). Statistical hypotheses (nonparametric tests) were tested using Statistica 8.0 software.Results. After reperfusion, pronounced involution of large zones of edema-swelling occurred in the DG of the hippocampal formation in white rats of the groups I, II, III after 7–14 days, and in rats of the group IV (ligation) the edema-swelling manifestations persisted for 30 days. Similar dynamics was recorded for the molecular and polymorphic layer of the DG, but the values of the integral variable chosen to assess the edema-swelling manifestations (the total intensity of the peak pixels) were different. The largest relative area of the brightest peaks was detected after bilateral ОССА (groups II and III) and LCCA (group IV), the smallest – after unilateral ОССА (group I). It is significant that after mild ischemia (20- and 30-min ОССА), the parameter increased only in 1 and 3 days, and then decreased. After more severe ischemia (40-min ОССА), similar manifestations of overhydration were observed in 1–7 days. With LССА, a high level of DG overhydration was noted throughout the observation period, as evidenced by the high relative area of all the brightest peaks. Statistically significant differences were found when comparing all groups for all periods, between groups in 14 and 30 days, between periods in groups I, II, and III (ANOVA Kruskal–Wallis test; Mann–Whitney U-test).Conclusion. After ОССА and LССА the restoration of the structures of the sensory input of the hippocampus (DG) occurs together with long-term preservation of signs of hyperhydration of the neuropil, perineuronal and perivascular spaces (legs of astrocytes). The extreme degree of these manifestations after LССА evidences a disruption of the drainage-detoxification function of astrocytes. In ОССА, long-term preservation of the edema-swelling manifestations is recommended to be considered as a condition for the implementation of the mechanisms of sanogenesis and restoration of the DG nervous tissue.