Electroacupuncture pretreatment attenuates blood-brain barrier disruption following cerebral ischemia/reperfusion

Disruption of the blood-brain barrier (BBB) and subsequent brain edema are major contributors to the pathogenesis of ischemic stroke, however, current clinical therapeutic methods remains unsatisfactory. Electroacupuncture (EA) pretreatment has a protective effect against cerebral ischemia/reperfusion (I/R). However, the underlying mechanisms remain to be fully elucidated. In the present study, the effect of EA pretreatment on BBB disruption was investigated in a focal I/R rat model. Male Sprague-Dawley rats (280-320 g) were pretreated with EA at the acupoint 'Baihui' (GV20) 30 min/day, for five days consecutively prior to focal cerebral I/R, which was induced by middle cerebral artery occlusion (MCAO) for 2 h. The results demonstrated that the infarction volume, brain water content and neurological deficits increased in the MCAO model rats at 3 h and 24 h post-reperfusion, and were attenuated significantly by EA pretreatment. Furthermore, electron microscopy examination confirmed a reduction in brain edema reduction in the EA pretreated rats. Western blot analysis revealed that the tight junction proteins between endothelial cells, including claudin-5, occludin, were significantly degraded, while the protein expression of phosphorylated (p-) caveolin-1 and p-Akt increased following reperfusion, all of which were alleviated by EA pretreatment. However, no significant differences were observed in the expression of caveolin-1 or Akt. Overall, the results demonstrated that EA pretreatment significantly reduced BBB permeability and brain edema, which were correlated with alleviation of the degradation of tight junction proteins and inhibition of the expression of p-caveolin-1 in the endothelial cells.