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

Abstract

Conditions associated with systemic infection, such as endotoxinemia, are known to increase the levels of pro‐inflammatory cytokines such as interleukin (IL)‐1 in the central nervous system. Systemic infection has been shown to be a common preexisting condition in patients with stroke. To examine a possible consequence of systemic infection, we used a novel electrochemical technique, which combines measurement of cerebral blood flow with measurement of superoxide anion concentrations, to examine the effect of pretreatment of pial vasculature with a proinflammatory cytokine, IL‐1β, on cerebral blood flow and superoxide anion concentration in a rat model of middle cerebral artery occlusion and reperfusion. In addition, neutrophil recruitment was measured using an immunohistochemical technique. Our results indicate that exposure of pial and cerebral vasculature to IL‐1β significantly accelerates recruitment of neutrophils, reduces cerebral blood flow, and increases superoxide anion concentration at the pial surface during reperfusion. These results support the idea that prior exposure of brain vasculature to IL‐1β results in acceleration of cerebrovascular injury by accelerating recruitment of neutrophils, which secrete superoxide anion, during reperfusion. This finding has possible implications for the treatment of stroke with reperfusion agents in patients with preexisting infections. J. Neurosci. Res. 60:795–803, 2000. © 2000 Wiley‐Liss, Inc.

Apocynin Attenuates Cerebral Infarction after Transient Focal Ischaemia in Rats

“…10,11 The interaction of superoxide with nitric oxide results in the production of peroxynitrite, one of the most harmful reactive oxygen species that causes neuronal tissue damage. Values are the mean ± SE.…”

Oxidative Stress in Rats With Heatstroke-Induced Cerebral Ischemia

“…Chang, MS, unpublished data, 2001). All these substances may cause the increase of reactive oxygen species 13,29 and result in ischemic neuronal damage in the brain.…”

Heterogeneity Affecting Outcome From Acute Stroke Therapy

“…If such patients could be identified, anti-immune therapy could be reserved for the patients most likely to sustain the greatest benefit in the acute setting. Our experimental work 55,56 has shown that neutrophil recruitment and superoxide generation are important only when ischemia duration is prolonged before reperfusion or when the ischemic tissue has been recently exposed to the inflammatory cytokine interleukin (IL)-1␤. In contrast, models with a shorter duration of ischemia or relatively minimal reperfusion show negligible neutrophil recruitment and contribution to outcome.…”

“…Yet, both clinical and experimental data suggest that recent infection/inflammation may be an important factor in outcome. Our laboratory 56 has studied whether administration of a specific inflammatory cytokine (IL-1␤) would accelerate development of reperfusion injury in an experimental model. Results showed that pretreatment with IL-1␤ on the cortical surface accelerated a number of pathological processes in experimental middle cerebral artery occlusion.…”

“…These events occurred after 60 to 90 minutes of ischemia, a time period that produces no measurable superoxide anion radical formation among non-1L-1␤-pretreated rats. Exposure to IL-1␤ accelerated the poor-reflow phenomenon 56 and reduced the ischemia time necessary to unleash superoxide anion radicals on reperfusion, an effect that could accelerate reactive oxygen species-mediated reperfusion damage to the vasculature and parenchyma. Thus, in the presence of upregulation of certain inflammatory cytokines such as might occur with recent infection, 161 reperfusion injury may be worsened by factors [162][163][164] discussed previously.…”