Monocyte chemoattractant protein-1 expressed in neurons and astrocytes during focal ischemia in mice

Focal cerebral ischemia elicits an inflammatory response characterized by t he infiltration and accumulation of leukocytes, as well as the secretion of inflammatory mediators (Clark et al., Brain Res. Bull., 35 (1994) 387-392; Garcia et al., Am. J. Pathol., 144 (1994) 188-199; Wang et al., J. Neuroch em. 71 (1998) 1194-1204). Leukocytes eliminate microbial invaders and necro tizing tissue debris, and can also turn against surrounding healthy tissue and exacerbate tissue injury (Furie and Randolph, Am. J. Pathol., 146 (1995 ) 1287-1301; Kochanek and Hallenbeck, Stroke 23 (1992) 1367-1379). Inflamma tory mediators are considered to play an important role in attracting and s timulating leukocytes (Weiss, N. Engl. J. Med., 320 (1989) 365-376). Monocy te chemoattractant protein-1 (MCP-1) functions as an inflammatory mediator, whose source and role in focal cerebral ischemia is worth studying. MCP-1, a potent chemoattractant factor, may play an important role in ischemia-in duced inflammatory response. The aim of the present study is to determine t he time course and cell type of MCP-1 protein expression after permanent fo cal ischemia in mice. ELISA and immunohistochemical staining were used to d etect the expression of MCP-1 protein after 0 h, 2 h, 4 h, 12 h, 1 day, 2 d ays, 3 days, 5 days and 7 days of middle cerebral artery occlusion (n=3-5 i n each group). Double-labeled fluorescent staining was used to examine the cellular localization of MCP-1. The results demonstrated that MCP-1 express ion was mainly observed in the ischemic core after 12 h of middle cerebral artery occlusion, then gradually increased and extended to the ischemic per ifocal area. MCP-1 expression peaked at 2 days and 3 days, and gradually de creased after 5 days of MCAO. Double-labeled immunostaining for MCP-1 and n euron specific enolase (NSE) or glial fibrillary acidic protein (GFAP) show ed that MCP-1 positive neurons were observed as early as 12 h of ischemia, while MCP-1 positive astrocytes were observed after 2 days of ischemia. The se results support the functional role of MCP-1 in ischemic brain injury an d reveal a distinct temporal and spatial expression of MCP-1 in cells belie ved to be neurons and astrocytes. (C) 2001 Elsevier Science B.V. All rights reserved.