Efeitos da cirurgia de ressecção hipocampal unilateral sobre os padrões de neurogênese e memória em ratos wistar adultos

Abstract

Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy in adults and hippocampal sclerosis (HE) is the most common pathological finding in this type of epilepsy. In TLE refractory cases, patients are indicated for unilateral resection surgery of the affected hippocampus which generally does not cause any cognitive impairment in patients. The existence of a hippocampus neurogenic area promotes the formation of new neurons even in adult human is known. A compensatory neurogenesis in the contralateral size of surgery could be responsible to explain a cognitive impairment absence in these patients. We aimed to investigate a possible compensatory neurogenesis in the hippocampus of the contralateral side of surgery in animal models submitted to unilateral hipocampectomy surgery as well to investigate learning and memory processes. For this goal, we have used 18 Wistar rats, divided into three groups, Control, G15 and G30 (N = 6 each). In the G15 and G30 surgical procedure of unilateral hipocampectomy were made. The animals were deeply anesthetized with a mixture of ketamine (80 mg / kg) and xylazine (10 mg / kg) until complete absence of ocular movements and interdigital reflex. They were transferred to stereotaxic apparatus and the dorsal hippocampus localized by X,Y coordinates. The adjacent cortex and hippocampus of the left hemisphere were completely removed surgically. The G15 and G30 animals were maintained for a survival period of 15 and 30 days, respectively, after surgery procedures. The control group was not submitted to the surgical procedure. To analyze if there was any impairment of learning and memory, the animals of the three experimental groups were submitted to the learning analysis in the eight arms radial maze for 7 days. After this period, the animals were perfused with 0.9% saline and 4% paraformaldehyde in 0.1M phosphate buffer. The brains were post-fixed for 48 hours and sectioned in a cryostat equipment at 30μm thick. Histochemical analysis was performed in sections of the right hippocampus for visualization of cell bodies of mature neurons (anti-NeuN) and migratory neuroblasts (anti-DCX). The results of the behavioral test did not show significant differences in learning and memory tasks between groups. Immunostaining otherwise showed labelling pattern differences between the G15 and G30 groups when compared to the control. The experimental groups showed a higher neuroblast cell density in the dentate gyrus and hilus when compared to the control group. These results leads us to consider that could exist a possible compensatory neurogenesis in the remaining hippocampus in these animals. In addition, unilateral hipocampetomy surgery did not responsible to cause any cognitive impairment in our experimental animals, using this methodology and this tool could be an important to investigate the neural bases that modulate ELT in human patients.