台大医院医生汤颂君日前研究发现，“免疫球蛋白”治疗急性栓塞性脑中风老鼠有显着效果。
据台湾《中国时报》报道，汤颂君前年至美国国家卫生研究院老年研究中心神经科学实验室进修。上述研究形成的论文发表于八月的美国国家科学期刊(PNAS)上。
汤颂君说，该研究室证实缺血性(即栓塞性)脑中风发生后，脑部发炎反应是引起神经细胞死亡主因之一，若能控制脑部发炎就能控制病情恶化。
据悉，免疫球蛋白是具有抗体活性的蛋白，可有效抑制体内免疫反应，SARS、严重肠病毒七十一型治疗就是以此为主，但从未应用于脑中风治疗。
此研究结果是新发现，因急性缺血性脑中风，目前仍无有效治疗方法，虽中风三小时以内，病患可于静脉注射血栓溶解剂，但在台湾只有1%的病患符合治疗条件。汤颂君有关脑中风的两篇论文引起美国国家卫生研究院高度重视，正申请人体临床实验及用药剂量与时机。（中新网）
原始出处:
Published online before print August 21, 2007, 10.1073/pnas.0700506104
PNAS | August 28, 2007 | vol. 104 | no. 35 | 14104-14109
BIOLOGICAL SCIENCES / NEUROSCIENCE
Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death
Thiruma V. Arumugam*,, Sung-Chun Tang*,, Justin D. Lathia*, Aiwu Cheng*, Mohamed R. Mughal*, Srinivasulu Chigurupati*, Tim Magnus*, Sic L. Chan*,, Dong-Gyu Jo*, Xin Ouyang*, David P. Fairlie¶, Daniel N. Granger||, Alexander Vortmeyer**, Milan Basta,, and Mark P. Mattson*,
*Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224; Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center 1400 Wallace Boulevard, Amarillo, TX 79106; Biomolecular Science Center, University of Central Florida, Orlando, FL 32816; ||Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130; Department of Neurology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin 640, Taiwan; ¶Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia; Neuronal Excitability Section and **Neurosurgical Division, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205
Edited by Michael V. L. Bennett, Albert Einstein College of Medicine, Bronx, NY, and approved July 24, 2007 (received for review January 18, 2007)
Stroke is among the three leading causes of death worldwide and the most frequent cause of permanent disability. Brain ischemia induces an inflammatory response involving activated complement fragments. Here we show that i.v. Ig (IVIG) treatment, which scavenges complement fragments, protects brain cells against the deleterious effects of experimental ischemia and reperfusion (I/R) and prevents I/R-induced mortality in mice. Animals administered IVIG either 30 min before ischemia or after 3 h of reperfusion exhibited a 50–60% reduction of brain infarct size and a 2- to 3-fold improvement of the functional outcome. Even a single low dose of IVIG given after stroke was effective. IVIG was protective in the nonreperfusion model of murine stroke as well and did not exert any peripheral effects. Human IgG as well as intrinsic murine C3 levels were significantly higher in the infarcted brain region compared with the noninjured side, and their physical association was demonstrated by immuno-coprecipitation. C5-deficient mice were significantly protected from I/R injury compared with their wild-type littermates. Exposure of cultured neurons to oxygen/glucose deprivation resulted in increased levels of C3 associated with activation of caspase 3, a marker of apoptosis; both signals were attenuated with IVIG treatment. Our data suggest a major role for complement-mediated cell death in ischemic brain injury and the prospect of using IVIG in relatively low doses as an interventional therapy for stroke.
C5a | cerebral cortex apoptosis | ischemic stroke | lymphocyte | microglia
Author contributions: T.V.A. and S.-C.T. and M.B. and M.P.M. contributed equally to this work; M.B. and M.P.M. designed research; T.V.A., S.-C.T., J.D.L., A.C., M.R.M., S.C., T.M., S.L.C., D.-G.J., X.O., D.N.G., and A.V. performed research; D.-G.J., X.O., D.P.F., and D.N.G. contributed new reagents/analytic tools; T.V.A., S.-C.T., and M.B. analyzed data; and M.B. and M.P.M. wrote the paper
