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 extends into the adjacent striatum, thalamus and cortex. NMDA-induced injury is marked by an acute microglial/monocyte response; the molecular signals that control this response and the role of activated microglia/monocytes in the progression of excitotoxic injury are unknown. Monocyte chemoattractant protein-1 (MCP-1) is a well-characterized chemokine that regulates monocyte chemotaxis and activation, and contributes to the pathogenesis of monocyte-dependent tissue injury in several disease models. We hypothesized that MCP-1 could be a regulator of the microglial/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 samples obtained from 7-day-old rats, evaluated 0-24 h after intra-hippocampal NMDA injection. MCP-1 mRNA expression was first detected at 2 h after lesioning, in the choroid fissure, adjacent to the lesioned hippocampus; levels of expression increased markedly in the lesioned hippocampus and adjacent structures within the first 16 h after NMDA injection, and then rapidly declined. In control animals that received intra-hippocampal saline injections, only minimal MCP-1 mRNA was detected, along the injection track. These results demonstrate that excitotoxic injury transiently induces MCP-1 gene expression in neonatal rat brain. The functional role of MCP-1 in the injured brain remains to be determined.
Szaflarski
J
J
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Ivacko
J
J
Liu
X H
XH
Warren
J S
JS
Silverstein
F S
FS
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D006624:Hippocampus; D006651:Histocytochemistry; D017403:In Situ Hybridization; D007267:Injections; D037102:Lectins / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D018932:Chemokine CCL2; D037102:Lectins; D012333:RNA, Messenger; D016202:N-Methylaspartate