geranylgeranylacetone and Cognition-Disorders

Cerebral ischemia and reperfusion (I/R) can trigger a cytotoxic cascade with overflow of reactive oxygen species, paradoxically causing neurological dysfunction, redox imbalance, inflammation and apoptosis. The present study aims to investigate the effect of geranylgeranylacetone(GGA) on cerebral I/R injury and the underlying mechanism. The results demonstrated that cerebral I/R increased the neurological function abnormality, brain edema, inflammation and oxidative injury in rats as well as the cognitive impairment, which was significantly reversed by GGA in a dose-dependent manner. GGA also suppressed the cell injury and apoptosis caused by cerebral I/R. Moreover, the protective effect of GGA was found to involve heat shock protein 90 (HSP90) and phosphorylated endothelial nitric oxide synthase (eNOS) expression and activity. Both the HSP90 and eNOS inhibitor abolished the effect of GGA. The data showed that GGA could protect rats against cerebral I/R injury, which may be related to the induction of HSP90 and activation of eNOS.

Topics: Animals; Apoptosis; Brain; Brain Edema; Brain Ischemia; Cognition Disorders; Disease Models, Animal; Diterpenes; HSP90 Heat-Shock Proteins; Malondialdehyde; Maze Learning; Neuroimmunomodulation; Neuroprotective Agents; Nitric Oxide Synthase Type III; Phosphorylation; Random Allocation; Rats, Sprague-Dawley; Reperfusion Injury; Treatment Outcome; Tumor Necrosis Factor-alpha