Electrochemical monitoring of superoxide anion production and cerebral blood flow: Effect of interleukin-1 beta pretreatment in a model of focal ischemia and reperfusion

Conditions associated with systemic infection, such as endotoxinemia, are k nown to increase the levels of proinflammatory cytokines such as interleuki n (IL)-1 in the central nervous system. Systemic infection has been shown t o be a common preexisting condition in patients with stroke. To examine a p ossible consequence of systemic infection, we used a novel electrochemical technique, which combines measurement of cerebral blood flow with measureme nt of superoxide anion concentrations, to examine the effect of pretreatmen t of pial vasculature with a proinflammatory cytokine, IL-1 beta, on cerebr al blood flow and superoxide anion concentration in a rat model of middle c erebral artery occlusion and reperfusion. In addition, neutrophil recruitme nt was measured using an immunohistochemical technique. Our results indicat e that exposure of pial and cerebral vasculature to IL-1 beta significantly accelerates recruitment of neutrophils, reduces cerebral blood flow, and i ncreases superoxide anion concentration at the pial surface during reperfus ion. These results support the idea that prior exposure of brain vasculatur e to IL-1 beta results in acceleration of cerebrovascular injury by acceler ating recruitment of neutrophils, which secrete superoxide anion, during re perfusion. This finding has possible implications for the treatment of stro ke with reperfusion agents in patients with preexisting infections. J. Neur osci. Res. 60: 795-803, 2000. (C) 2000 Wiley-Liss, Inc.