Treatment with Enriched Environment Reduces Neuronal Apoptosis in the Periinfarct Cortex after Cerebral Ischemia/Reperfusion Injury

Abstract

Background/Aims: Enriched environment (EE) has been reported to exert neuroprotective effect in animal models of ischemic stroke. However, the underlying mechanism remains unclear. The purpose of this study was to investigate the effect of EE treatment on neuronal apoptosis in the periinfarct cortex after cerebral ischemia/reperfusion (I/R) injury. Methods: The cerebral I/R injury was established by middle cerebral artery occlusion (MCAO). A set of behavioral tests including the modified neurological severity score (mNSS), limb-placing test and foot-fault test were conducted. The infarct volume and the neuronal survival rate were evaluated by Nissl staining. The morphology and ultrastructure of ischemic neurons was examined by transmission electron microscopy. Neuronal apoptosis was assessed by double labeling of TdT-mediated dUTP-biotin nick end labeling (TUNEL) with NeuN. The expressions of apoptosis-related proteins were tested by western blotting and immunohistochemical labeling. Results: EE treatment improved neurological function, reduced infarct volume, increased neuronal survival rate and alleviated the morphological and ultrastructural damage of neurons (especially mitochondria) after I/R injury. EE treatment reduced the neuronal apoptosis, increased B cell lymphoma/leukemia-2 (Bcl-2) protein levels while decreased Bcl-2-associated X protein (Bax), cytochrome c, caspase-3 expressions and Bax/Bcl-2 ratio in the periinfarct cortex after cerebral I/R injury. Conclusion: Our findings suggest that EE treatment inhibits neuronal apoptosis in the periinfarct cortex after focal cerebral I/R injury, which may be one of the possible mechanisms underlying the neuroprotective effects of EE.

By Activating Akt/eNOS Bilobalide B Inhibits Autophagy and Promotes Angiogenesis Following Focal Cerebral Ischemia Reperfusion

“…Since apoptosis and autophagy are now relatively well defined mechanisms of stroke mediated brain injury [25,26], readily available compounds that are able to combat these pathways are desirable subjects of further studies to develop therapeutic strategies to treat stroke patients. In this study, we subjected rats to transient MCAO and studied the effects of bilobalide in post MCAO recovery.…”

Current Mechanistic Concepts in Ischemia and Reperfusion Injury

“…In parallel, Bax and Bak are processed and inserted into the mitochondrial membrane to release downstream pro-apoptotic proteins such as cytochrome c, Smac/Diablo, HTRA2/Omi, apoptosis-inducing factor, and endonuclease G. Cytochrome c binds apoptotic protease activating factor 1 (APAF-1) to activate pro-caspase-9 to form the apoptosome. The apoptosome induces a caspase cascade to promote apoptosis via activation of caspase-9 [86]. Endo G also interacts with AIF to cause DNA fragmentation.…”

Overexpression of Myocardin-related transcription factor-A attenuated middle cerebral artery occlusion/reperfusion-induced apoptosis via the Mcl-1/Cyt C/cleaved caspase 3 pathway

“…[6][7][8][9][10] Most studies have indicated that cell apoptosis plays a vital role in the mechanisms underlying I/R-induced neuronal damage. 11 Therefore, inhibiting apoptosis may be a promising direction for neuroprotection in I/R injury.…”