EXCITOTOXIC INJURY INDUCES MONOCYTE CHEMOATTRACTANT PROTEIN-1 EXPRESSION IN NEONATAL RAT-BRAIN

Intra-hippocampal injection of NMDA (12.5 nmol) in postnatal day 7 (P7 ) rats results in neuronal necrosis and hippocampal atrophy; injury ex tends into the adjacent striatum, thalamus and cortex. NMDA-induced in jury is marked by an acute microglial/monocyte response; the molecular signals that control this response and the role of activated microgli a/monocytes in the progression of excitotoxic injury are unknown. Mono cyte chemoattractant protein-1 (MCP-1) is a well-characterized chemoki ne that regulates monocyte chemotaxis and activation, and contributes to the pathogenesis of monocyte-dependent tissue injury in several dis ease models. We hypothesized that MCP-1 could be a regulator of the mi croglial/monocyte response to excitotoxic injury in neonatal rat brain . To determine if intra-hippocampal NMDA injections induced MCP-1 mRNA expression, in situ hybridization assays were performed in brain samp les obtained from 7-day-old rats, evaluated 0-24 h after intra-hippoca mpal NMDA injection. MCP-1 mRNA expression was first detected at 2 h a fter lesioning, in the choroid fissure, adjacent to the lesioned hippo campus; levels of expression increased markedly in the lesioned hippoc ampus and adjacent structures within the first 16 h after NMDA injecti on, and then rapidly declined. In control animals that received intra- hippocampal saline injections, only minimal MCP-1 mRNA was detected, a long the injection track. These results demonstrate that excitotoxic i njury transiently induces MCP-1 gene expression in neonatal rat brain. The functional role of MCP-1 in the injured brain remains to be deter mined. (C) 1998 Elsevier Science B.V.