Excitotoxic injury induces monocyte chemoattractant protein-1 expression in neonatal rat brain

Brain Res Mol Brain Res. 1998 Apr;55(2):306-14. doi: 10.1016/s0169-328x(98)00013-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn / metabolism*
  • Brain / drug effects
  • Brain / metabolism*
  • Chemokine CCL2 / biosynthesis*
  • Chemokine CCL2 / genetics
  • Hippocampus
  • Histocytochemistry
  • In Situ Hybridization
  • Injections
  • Lectins / metabolism
  • N-Methylaspartate / toxicity*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley


  • Chemokine CCL2
  • Lectins
  • RNA, Messenger
  • N-Methylaspartate