Geranylgeranylacetone exerts neuroprotective roles through medicating the phosphatidylinositol-3 kinase/Akt signaling pathway in an intracerebral hemorrhage rat model.

AIM

Previous studies have demonstrated that geranylgeranylacetone exerts neuroprotective effects in experimental intracerebral hemorrhage. This study is designed to explore the underlying mechanism.

MATERIALS AND METHODS

One hundred and eighty male Sprague-Dawley rats were subjected to intracerebral hemorrhage by stereotactic injection of collagenase and were pretreated without or with different doses of geranylgeranylacetone. At 6 h, 24 h, 48 h, 72 h and 7 days after the operation, the neurological deficits were examined with the scoring scale method. To explore the underlying mechanism, wortmannin (Wort), a specific phosphatidylinositol-3 kinase (PI3K) inhibitor, was used. The protein expression of Akt was determined by Western blotting. The brain water content and the hematoma volume assessment were measured and compared among the different groups.

RESULTS

We first found that geranylgeranylacetone pretreatment significantly reduced neurological deficit in intracerebral hemorrhage rats, indicating its neuroprotective role. Then, we found wort treatment significantly decreased the geranylgeranylacetone-induced Akt expression level in intracerebral hemorrhage rats. Besides, wort not only reversed the effects of geranylgeranylacetone on neurological function, but also reversed the effects of geranylgeranylacetone on reducing brain edema and decreasing hematoma volume in intracerebral hemorrhage rats.

CONCLUSION

Geranylgeranylacetone exerts neuroprotective roles, at least partially, through medicating the PI3K/Akt signaling pathway in an experimental intracerebral hemorrhage rat model.