HSPB8 over ‐expression prevents disruption of blood–brain barrier by promoting autophagic flux after cerebral ischemia/reperfusion injury

This study focused on the effect of intracerebroventricular (i.c.v) delivery of lenti ‐HSPB8 virus against neurological injury in a rat model of cerebral I/R and explored the underlying mechanism. We found that lentivirus i.c.v injection‐induced HSPB8 over‐expression strongly alleviated infarct volume, improved neurobehavioral outcomes, and reduced brain edema in rat middle cer ebral artery occlusion/reperfusion (MCAO/R) model. Concomitantly, HSPB8 over‐expression noticeably prevented blood–brain barrier (BBB) disruption after cerebral I/R injury as indicated by the reduction in Evans blue leakage and IgG detection in the ipsilateral hemisphere compared with the vehicl e group. Moreover, immunoblotting and immunofluorescence staining of tight junction proteins claudin‐5 and occludin showed that HSPB8 over‐expression prevented the degradation of these proteins induced by MCAO/R, which indicated the protective effect of HSPB8 on BBB. Western blotting and immunos taining techniques were also utilized to analyze the expression of the markers of autophagy. We found that HSPB8 over‐expression promoted autophagic flux, evidenced by increased ratio of LC3 I/II, accumulation of Beclin‐1 expression and enhanced p62 degradation. i.c.v injection of 15 μg autoph agy inhibitor 3‐methyladenine (3‐MA) was applied at the onset of reperfusion. The results showed that 3‐MA elicited a significant loss of the protective effect of HSPB8 against MCAO/R‐induced neurologic...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Original Article Source Type: research