XQ-1H Suppresses Neutrophils Infiltration and Oxidative Stress Induced by Cerebral Ischemia Injury Both In Vivo and In Vitro

Cerebral ischemia/reperfusion injury plays an important role in the development of tissue injury after acute stroke, including neutrophils adhesion and infiltration, inflammation and oxidative stress. 10-O-( N , N -dimethylaminoethyl)-ginkgolide B methanesulfonate (XQ-1H) is a novel ginkdolide B derivative. In this study, we investigated the anti-inflammatory and anti-oxidative activities of XQ-1H in vivo and vitro. In our study, rats were treating with XQ-1H (31.2, 15.6 and 7.8 mg/kg) after middle cerebral artery occlusion surgery. Primary cultured cortical rat neurons were treated with Na 2 S 2 O 4 for 1.5 h to mimic hypoxia and reoxygenation injury in vitro. Cortical neurons were preincubated with XQ-1H (100, 10, 1 μM) 24 h before hypoxic injury. Brain edema was evaluated by brain water content. Neutrophil infiltration was determined by fluorescence imaging method and myeloperoxidase assay. Intercellular adhesion molecule 1 (ICAM-1) and matrix metallopeptidase 9 (MMP-9) expressions were examined by immunohistochemistry analysis. Neuronal injury was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, lactate dehydrogenase releasing and lactic acid content. The anti-oxidative effects of XQ-1H were evaluated by superoxide dismutase (SOD) activity and malondialdehyde content in ischemic brain and neuron cultures subjected to hypoxia/reoxygenation procedure. Results showed that XQ-1H reduced neutrophils infiltration to ischemic brain, which might result from down regulation of inflammatory mediators, such as ICAM-1 and MMP-9. In addition, an antioxidative effect of XQ-1H was observed in cortical neuron and brain homogenates by enhancing SOD activity and inhibiting lipid peroxidation. These results indicated that XQ-1H possessed a protective effect against cerebral ischemia, especially on neutrophil infiltration and oxidative stress.