Stroemer R P, Rothwell N J
School of Biological Sciences, University of Manchester, United Kingdom.
J Cereb Blood Flow Metab. 1998 Aug;18(8):833-9. doi: 10.1097/00004647-199808000-00003.
Interleukin-1beta (IL-1beta) has been implicated in ischemic brain damage. The site of action of IL-1beta in such damage is not known, but we have demonstrated previously that injection of the interleukin-1 receptor antagonist (IL-1ra) in the striatum but not the cortex of rats inhibits damage caused by permanent middle cerebral artery occlusion. The present study investigated the site of action of IL-1beta on ischemic damage by examining the effects of intracerebroventricular, striatal, or cortical injection of recombinant IL-1beta at the onset of permanent middle cerebral artery occlusion in the rat. Intracerebroventricular injection of IL-1beta (2.5 ng) significantly increased infarct volume in the striatum (35%, P < 0.0001) and in the cortex (44%, P < 0.0001) compared with vehicle treatment. Direct injection of IL-1beta into the striatum also increased infarct volume in both the striatum (36%, P < 0.0001) and the cortex (38%, P < 0.0001), whereas injection of IL-1beta into the cortex failed to affect infarct volume in either the striatum or the cortex. Cortical injection of a higher dose of IL-1beta (20 ng) also failed to affect ischemic damage in either the striatum or the cortex. Injection of IL-1beta into the striatum contralateral to the infarction had no effect on striatal damage in the ischemic hemisphere, but did increase cortical damage by 18% (P < 0.0001). In separate groups of animals, IL-1beta (2.5 ng) was injected into either the striatum or the cortex, and body temperature was recorded continuously in conscious free-moving animals by remote telemetry. Injection of IL-1beta at either site failed to influence body temperature, suggesting that exacerbation of brain damage by striatal injection of IL-1beta is not caused by effects on body temperature. These results imply that IL-1beta exacerbates ischemic damage by specific actions in the striatum where it can influence damage at distant sites in the cortex.
白细胞介素-1β（IL-1β）与缺血性脑损伤有关。IL-1β在这种损伤中的作用位点尚不清楚，但我们之前已经证明，在大鼠纹状体而非皮层注射白细胞介素-1受体拮抗剂（IL-1ra）可抑制永久性大脑中动脉闭塞所致的损伤。本研究通过在大鼠永久性大脑中动脉闭塞开始时，检查脑室内、纹状体或皮层注射重组IL-1β的效果，来研究IL-1β对缺血性损伤的作用位点。与注射赋形剂相比，脑室内注射IL-1β（2.5 ng）显著增加了纹状体的梗死体积（35%，P < 0.0001）和皮层的梗死体积（44%，P < 0.0001）。将IL-1β直接注射到纹状体也增加了纹状体（36%，P < 0.0001）和皮层（38%，P < 0.0001）的梗死体积，而将IL-1β注射到皮层未能影响纹状体或皮层的梗死体积。皮层注射更高剂量的IL-1β（20 ng）也未能影响纹状体或皮层的缺血性损伤。将IL-1β注射到梗死对侧的纹状体对缺血半球的纹状体损伤没有影响，但确实使皮层损伤增加了18%（P < 0.0001）。在单独的动物组中，将IL-1β（2.5 ng）注射到纹状体或皮层，并通过远程遥测连续记录清醒自由活动动物的体温。在任一部位注射IL-1β均未影响体温，这表明纹状体注射IL-1β导致脑损伤加重并非由对体温的影响所致。这些结果意味着，IL-1β通过在纹状体中的特定作用加剧缺血性损伤，在纹状体中它可影响皮层远处部位的损伤。
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