Apocynin improves outcome in experimental stroke with a narrow dose range

作者：Tang X N; Cairns B; Cairns N; Yenari M A^*

来源：Neuroscience, 2008, 154(2): 556-562.

DOI：10.1016/j.neuroscience.2008.03.090

• apocynin
• superoxide
• NADPH oxidase
• stroke
• brain hemorrhage

Inflammation following ischemic stroke is known to contribute to injury. NADPH oxidase (NOX) is a major enzyme system originally studied in immune cells that leads to superoxide (O center dot(-)) generation. Apocynin is a NOX inhibitor that has been studied as a potential treatment in experimental stroke. Here we explored the effect of different doses of apocynin in a mouse model of 2 h transient middle cerebral artery occlusion (tMCAO) followed by 22 h reperfusion. Apocynin, given i.v. at a dose of 2.5 mg/kg 30 min before reperfusion, improved neurological P<0.01), reduced infarct volume (P<0.05), and reduced the incidence of cerebral hemorrhage (P<0.05), but not at higher doses of 3.75 and 5 mg/kg, where it actually increased brain hemorrhage. Apocynin also tended to reduce mortality at the lower dose, but not at higher doses. Using hydroethine fluorescence to delineate O center dot(-) in the brain, neurons and some microglia/macrophages, but not vascular endothelial cells were found to contain O center dot(-). Apocynin at protective doses markedly prevented ischemia-induced increases in O center dot(-). Our data suggested that apocynin can protect against experimental stroke, but with a narrow therapeutic Published by Elsevier Ltd on behalf of IBRO.

• 出版日期2008-6-23