Yamasaki Y, Matsuura N, Shozuhara H, Onodera H, Itoyama Y, Kogure K
Department of Neurology, Tohoku University School of Medicine, Miyagi, Japan.
Stroke. 1995 Apr;26(4):676-80; discussion 681. doi: 10.1161/01.str.26.4.676.
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.
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-1 beta (rhIL-1 beta), anti-interleukin-1 beta neutralizing antibodies (anti-IL-1 beta), 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.
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-1 beta 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-1 beta; P < .01). rhIL-1 beta 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-1 beta 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 micrograms anti-IL-1 beta; P < .01). The number of neutrophils that infiltrated into ischemic areas also tended to decrease with anti-IL-1 beta or ZnPP treatment.
Application of rhIL-1 beta augmented the increase of brain water content, and application of anti-IL-1 beta depressed the increase of water content. These results tended to correlate with the neutrophilic infiltration into the parenchyma. It thus appears that IL-1 beta may play an important role in ischemic brain damage after reperfusion.
有人提出白细胞介素 -1（IL -1）是一种强效的炎症介质，且能在脑实质中合成并分泌。本研究的目的是评估IL -1对局灶性脑缺血后脑水肿形成的作用。
在大脑中动脉闭塞60分钟并再灌注后，测量大鼠脑含水量以评估缺血性脑损伤。观察外源性应用重组人白细胞介素 -1β（rhIL -1β）、抗白细胞介素 -1β中和抗体（抗IL -1β）和IL -1阻断剂锌原卟啉（ZnPP）对脑含水量的影响，并采用组织学技术测量梗死面积以及浸润到脑内的炎性细胞数量。
短暂性缺血导致大脑中动脉供血的皮质以及尾状核壳核的背侧和腹侧区域脑含水量显著增加、出现坏死和中性粒细胞浸润。再灌注后立即向左脑室内注射rhIL -1β以剂量依赖方式显著增强了这三个区域的缺血性脑水肿形成（用10 ng rhIL -1β处理的大鼠，尾状核壳核背侧和腹侧分别为88.4±0.7%和86.6±0.4%；P <.01）。rhIL -1β还增加了脑梗死面积，并且倾向于增加缺血区域浸润的中性粒细胞数量以及黏附在内皮细胞上的中性粒细胞数量。相反，向左脑室内给予抗IL -1β和ZnPP可减轻缺血后脑含水量的增加并减小脑梗死面积（用10μg抗IL -1β处理的大鼠，尾状核壳核背侧和腹侧分别为83.5±2.0%和79.9±2.0%；P <.01）。抗IL -1β或ZnPP处理后，浸润到缺血区域的中性粒细胞数量也倾向于减少。
应用rhIL -1β增加了脑含水量，而应用抗IL -1β抑制了含水量的增加。这些结果与实质内的中性粒细胞浸润倾向相关。因此，IL -1β似乎在再灌注后缺血性脑损伤中起重要作用。
