L-3n-butylphthalide maintains BBB permeability and attenuates cerebral ischemia-reperfusion injury in rats by increasing PGC-1α levels.

AIM: The aim of the present study was to investigate the possible mechanisms of DL-3-n-butylphthalide (NBP) in maintaining the stability of the blood-brain barrier (BBB) and attenuating cerebral ischemia-reperfusion injury (CIRI) by increasing the levels of PGC-1α.

METHODS

A model of middle cerebral artery occlusion/reperfusion (MCAO/R) injury was established using Sprague-Dawley rats. The rats were divided into sham, MCAO/R, NBP, Vehicle and SR-18292 groups. 2,3,5-Triphenyltetrazolium chloride staining, hematoxylin and eosin (H&E) staining, and Evans Blue staining were performed to observe the volume of cerebral infarction, status of pathological injury, and BBB permeability of the brain tissue, respectively. Immunofluorescence staining and western blot analysis were performed to evaluate the expression of vascular endothelial cell markers (vWF and CD31), tight junction (TJ) protein markers (claudin5 and occludin), and PGC-1α.

RESULTS

H&E staining showed that the brain tissues of MCAO/R rats showed worsening vacuolar degeneration and necrosis. NBP reduced infarct volume, decreased the level of BBB extravasation, increased vascular density, and promoted the expression of TJs. Concurrently, NBP activated PGC-1α levels in rats subjected to MCAO/R. Downregulation of PGC-1α levels by PGC-1α inhibitors (SR-18292) could promote BBB permeability, infarct volume, and neurological deficits in the MCAO/R model.

CONCLUSIONS

The present study demonstrates that NBP plays a role in maintaining the stability of the BBB and attenuates CIRI by increasing PGC-1α levels as well as by increasing the levels of vascular endothelial cells and TJ markers.