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(Stroke. 1995;26:676-681.)
© 1995 American Heart Association, Inc.
Articles |
Interleukin-1 as a Pathogenetic Mediator of Ischemic Brain Damage in Rats
From the Department of Neurology, Institute of Brain Disease, Tohoku University School of Medicine, Sendai, Miyagi (Y.Y., H.S., H.O., Y.I.); the Hanno Research Center, Taiho Pharmaceutical Co Ltd, Hanno, Saitama (N.M.); and the Institute of Neuropathology, Kumagaya, Saitama (K.K.), Japan.
Correspondence to Y. Yamasaki, Department of Neurology, Institute of Brain Disease, Tohoku University School of Medicine, Sendai, Miyagi 980, Japan.
Background and Purpose It has been suggested that interleukin-1 (IL-1) is a potent inflammatory mediator and that it is synthesized and secreted into the brain parenchyma. The aim of the present study is to evaluate the contribution of IL-1 to brain edema formation after focal brain ischemia.
Methods The brain water content was measured to evaluate postischemic brain injury in rats after 60 minutes of middle cerebral artery occlusion and reperfusion. The effects of exogenous application of recombinant human interleukin-1ß (rhIL-1ß), anti–interleukin-1ß neutralizing antibodies (anti–IL-1ß), and the IL-1 blocker zinc protoporphyrin (ZnPP) on brain water content were observed, and histological technique was used to measure the infarction size and number of inflammatory cells infiltrated into the brain.
Results Transient ischemia induced marked increase of brain water content, necrosis, and neutrophilic infiltration in the cortex perfused by the middle cerebral artery and the dorsal and ventral areas of the caudate putamen. Injection of rhIL-1ß into the left lateral ventricle immediately after reperfusion markedly enhanced ischemic brain edema formation in these three areas in a dose-dependent manner (88.4±0.7% and 86.6±0.4% in the dorsal and ventral parts of the caudate putamen, respectively, in rats treated with 10 ng rhIL-1ß; P<.01). rhIL-1ß also increased the size of the brain infarction, and it tended to increase the number of infiltrating neutrophils in ischemic areas and the number of neutrophils adherent to the endothelium. In contrast, administration of anti–IL-1ß and ZnPP into the left cerebral ventricle attenuated the postischemic increase of brain water content and decreased the size of brain infarction (83.5±2.0% and 79.9±2.0% in the dorsal and ventral parts of the caudate putamen, respectively, in rats treated with 10 µg anti–IL-1ß; P<.01). The number of neutrophils that infiltrated into ischemic areas also tended to decrease with anti–IL-1ß or ZnPP treatment.
Conclusions Application of rhIL-1ß augmented the increase of brain water content, and application of anti–IL-1ß depressed the increase of water content. These results tended to correlate with the neutrophilic infiltration into the parenchyma. It thus appears that IL-1ß may play an important role in ischemic brain damage after reperfusion.
Key Words: brain edema • cerebral ischemia, focal • interleukins • rats
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