Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition

Abstract

Sublethal ischemic preconditioning (IPC) is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration), 5×5 min (5 min duration, 2 episodes, 15-min interval), 5×5×5 min (5 min duration, 3 episodes, 15-min intervals), and 15 min (15 min duration), and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1)-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R) injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis.

Metformin improves anxiety-like behaviors through AMPK-dependent regulation of autophagy following transient forebrain ischemia

“…Our study cleared that the levels of autphagic related proteins: LC3B, Atg7, Atg12-Atg5 complex and beclin-1 were decreased in global cerebral ischemia and metformin pretreatment for 2 weeks increased these factors following global cerebral ischemia. It was declared that reduction of autophagy in ischemic group might be related to activation of apoptotic pathway (Ashabi et al 2014a;Xia et al 2013). Furthermore, activation of AMPK amplified protective role of autophagy.…”

Combination of Ginsenoside Rg1 and Bone Marrow Mesenchymal Stem Cell Transplantation in the Treatment of Cerebral Ischemia Reperfusion Injury in Rats

“…Positive cells were counted using the CIAS-1000 cell image analysis system. The average positive cell number was counted from each perspective [17].…”

Ghrelin protects adult rat hippocampal neural stem cells from excessive autophagy during oxygen-glucose deprivation

“…In fact, dysregulated autophagy has been involved in many human disease states. Also as a bulk cellular degradation pathway, autophagy has been widely reported in its neuroprotective potential [11][12][13] and autophagy is thought to be a protective mechanism that sustain cell survival under stress conditions. By contrast, altercation exist whether excessive autophagy activity contribute to autophagy induced cell death [14][15][16], when autophagy is excessively induced, it can result in autophagic cell death, type II programmed cell death (PCD).…”