Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia
Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia
复制标题
DOI：
10.1073/pnas.94.20.10873
复制
发表时间：
1997-09-30
影响因子：
11.1
通讯作者：
Hallenbeck, JM
中科院分区：
文献类型：
--
作者：
Becker, KJ;McCarron, RM;Hallenbeck, JM
免疫机制参与了脑缺血损伤的发生。由于全身副作用，治疗免疫抑制的选择有限。我们试图通过口服对髓鞘碱性蛋白(MBP)的耐受来实现大脑的免疫抑制。Lewis大鼠在大脑中动脉闭塞(MCAO)前3h给予小剂量牛MBP或卵清蛋白(1 mg，5次)。第三组动物对MBP致敏，但没有在中风后时期存活下来。免疫组织化学结果显示，耐受组小鼠脑内T细胞产生转化生长因子β1，在体内证实了对MBP的耐受性，表现为脾细胞对刀豆蛋白A、脂多糖和MBP的体外增殖。两组患者的全身转化生长因子p1水平相当。术后24小时皮质酮水平在所有假手术动物和缺血对照组动物中均升高，而在缺血耐受动物中未见升高。这些结果表明，抗原特异性的免疫反应调节缩小了局灶性脑缺血后的梗塞面积，而对相同抗原的敏化实际上可能会恶化预后。
Immune mechanisms contribute to cerebral ischemic injury. Therapeutic immunosuppressive options are limited due to systemic side effects. We attempted to achieve immunosuppression in the brain through oral tolerance to myelin basic protein (MBP). Lewis rats were fed low-dose bovine MBP or ovalbumin (1 mg, five times) before 3 h of middle cerebral artery occlusion (MCAO). A third group of animals was sensitized to MBP but did not survive the post-stroke period. Infarct size at 24 and 96 h after ischemia was significantly less in tolerized animals, Tolerance to MBP was confirmed in vivo by a decrease in delayed-type hypersensitivity to MBP, Systemic immune responses, characterized in vitro by spleen cell proliferation to Con A, lipopolysaccharide, and MBP, again confirmed antigen-specific immunologic tolerance, Immunohistochemistry revealed transforming growth factor pi production by T cells in the brains of tolerized but not control animals. Systemic transforming growth factor pi levels were equivalent in both groups. Corticosterone levels 24 h after surgery were elevated in all sham operated animals and ischemic control animals but not in ischemic tolerized animals. These results demonstrate that antigen-specific modulation of the immune response decreases infarct size after focal cerebral ischemia and that sensitization to the same antigen may actually worsen outcome.