Zhan Xinhua, Kim Charles, Sharp Frank R
Department of Neurology and M.I.N.D. Institute, University of California at Davis, Sacramento, CA 95817, USA.
Brain Res. 2008 Oct 9;1234:183-97. doi: 10.1016/j.brainres.2008.07.094. Epub 2008 Aug 5.
This study examined very brief focal ischemia that simulates transient ischemic attacks (TIAs) that occur in humans. Adult rats were subjected to sham operations or 5 min, 10 min, or 2 h of middle cerebral artery (MCA) ischemia using the suture (thread) model. Hsp70 protein was induced 24 h, 48 h and 72 h later in neurons throughout the entire MCA territory in many but not all animals. Following 5- and 10-minute MCA occlusions, 9 of 32 animals (28%) had microinfarcts mostly in dorsal lateral striatum. Uncommon Hsp70 stained intracellular cytoplasmic inclusions, some of which co-localized with activated caspase-3, were detected in microglia, macrophages, astrocytes and oligodendrocytes. Hsp70 stained neurons were TUNEL negative at 24 h and 48 h whereas some Hsp70 stained neurons were TUNEL positive at 72 h after reperfusion. Hsp70 positive, activated "bushy" microglia and Hsp70 negative, activated "polarized" or rod-shaped microglia were located outside of the microinfarcts. Thus, experimental focal ischemia simulating TIAs can: induce Hsp70 protein throughout the ischemic vessel territory; produce Hsp70 protein positive glial inclusions; activate Hsp70 positive and negative microglia; and cause microinfarcts in some animals.
本研究检测了模拟人类短暂性脑缺血发作(TIA)的极短暂局灶性缺血。成年大鼠接受假手术,或使用缝线模型进行5分钟、10分钟或2小时的大脑中动脉(MCA)缺血。在许多但并非所有动物中,缺血24小时、48小时和72小时后,整个MCA区域的神经元中均诱导出Hsp70蛋白。在MCA闭塞5分钟和10分钟后,32只动物中有9只(28%)出现微梗死,主要位于背外侧纹状体。在小胶质细胞、巨噬细胞、星形胶质细胞和少突胶质细胞中检测到罕见的Hsp70染色的细胞内细胞质包涵体,其中一些与活化的caspase-3共定位。再灌注后24小时和48小时,Hsp70染色的神经元TUNEL阴性,而72小时时一些Hsp70染色的神经元TUNEL阳性。Hsp70阳性、活化的“浓密型”小胶质细胞和Hsp70阴性、活化的“极化型”或杆状小胶质细胞位于微梗死灶之外。因此,模拟TIA的实验性局灶性缺血可:在整个缺血血管区域诱导Hsp70蛋白;产生Hsp70蛋白阳性的胶质细胞包涵体;激活Hsp70阳性和阴性小胶质细胞;并在一些动物中导致微梗死。