Autophagy regulates intracerebral hemorrhage induced neural damage via apoptosis and NF-κB pathway.

Autophagy can be a pro-survival or a pro-death mechanism depending on the context. The role of autophagy in intracerebral hemorrhage (ICH) remains elusive. In this study, in vivo and in vitro experiments have been carried out to investigate the role of autophagy after ICH. Collagenase-induced ICH model in mouse was made for in vivo experiments. Primary cortical neurons cultures were exposed to hemin to mimic ICH in vitro. 3-Methyladenine (3-MA) and rapamycin (RAP) were administrated both in vivo and in vitro. We first measured brain water content and cell death after ICH in model. Expression of LC3, p62/SQSTM1 (p62), Beclin1, Caspase3 and Bcl-2, which have been found related to autophagy and apoptosis, were assessed both in vivo and in vitro. Furthermore, NF-κB was detected to explore the potential mechanisms. We found brain edema in ICH model in mouse and the number of Propidium Iodide (PI)-positive cells both in vivo and in vitro were decreased by 3-MA pretreated. Simultaneously, both in vivo and in vitro, 3-MA significantly decreased the expression of LC3-II and Beclin-1, and maintained p62 at high level after ICH. Furthermore, pretreatment with 3-MA downregulated the level of cleaved caspase-3 but upregulated the Bcl-2 level. Conversely, RAP pretreatment reversed all these results above. These data indicated that autophagy activation may deprave ICH induced brain injury in ICH model and neuro-damage may be related to regulating of NF-κB pathway and thereby promote inflammation and apoptosis, thus might provide novel therapeutic interventions for ICH.