Neurogênese endógena induzida por acidente vascular encefálico experimental após inibição da ativação microglial/macrofágica com o anti-inflamatório indometacina

Stroke results from the transitory or permanent reduction of cerebral blood flow. It can be classified as hemorrhagic or ischemic. Ischemic stroke is responsible for around 87% of all cases. This acute neural disorder is the second cause of mortality and disability around the world and the main cause of death in Brazil. It has been shown that neuroblasts migrate to the ischemic striatum following middle cerebral artery occlusion (MCAO) and partially replace neurons lost during ischemia. Nevertheless, most of the migrating neuroblasts die in the first weeks following MCAO and inflammatory events, mainly microglia activation, may underlie neuroblast death. In this study, we investigated the effects of the nonsteroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation and adult neurogenesis following experimental MCAO in adult rats. Animals were submitted to endothelin-1 induced- MCAO and treated (i.p) with indomethacin (N=8) or sterile saline (N=8) for 7 days and perfused at 8 or 14 days. Immunohistochemistry was performed to assess neuronal loss (anti-NeuN), microglial activation (anti-Iba1 and ED1) and migrating neuroblasts (anti-DCX). The numbers of NeuN, ED1 and DCX positive cells per field were counted in the ischemic striatum or subventricular zone. Indomethacin treatment reduced microglial activation in general and the number of ED1+ cells at both 8 and 14 days (±6,9 and ±3,0 cells respectively) postinjury, compared to control (±7,9 or ±6,5 cells, p<0.001, ANOVA-Tukey). There was an increase in the number of DCX+ cells in both subventricular zone (SVZ) and striatum at the same survival times. There was no difference in the number of NeuN positive cells between groups in all investigated survival times. The results show that indomethacin treatment induces inhibition of microglial activation concomitant with increased neuroblast proliferation and migration following MCAO. This is a promising outcome, considering that indomethacin is already used in non-neural human diseases and ...