Acute excitotoxic injury induces expression of monocyte chemoattractant protein-1 and its receptor, CCR2, in neonatal rat brain.
Chemokines are a family of structurally related cytokines that activate and recruit leukocytes into areas of inflammation. The "CC" chemokine, monocyte chemoattractant protein (MCP)-1 may regulate the microglia/monocyte response to acute brain injury. Recent studies have documented increased expression of MCP-1 in diverse acute and chronic experimental brain injury models; in contrast, there is little information regarding expression of the MCP-1 receptor, CCR2, in the brain. In the neonatal rat brain, acute excitotoxic injury elicits a rapid and intense microglial response. To determine if MCP-1 could be a regulator of this response, we evaluated the impact of excitotoxic injury on MCP-1 and CCR2 expression in the neonatal rat brain. We used a reproducible model of focal excitotoxic brain injury elicited by intrahippocampal injection of NMDA (10 nmol) in 7-day-old rats, to examine injury-induced alterations in MCP-1 and CCR2 expression. RT-PCR assays demonstrated rapid stimulation of both MCP-1 and CCR2 mRNA expression. MCP-1 protein content, measured by ELISA in tissue extracts, increased >30-fold in lesioned tissue 8-12 h after lesioning. CCR2 protein was also detectable in tissue extracts. Double-immunofluorescent labeling enabled localization of CCR2 both to activated microglia/monocytes in the corpus callosum adjacent to the lesioned hippocampus and subsequently in microglia/monocytes infiltrating the pyramidal cell layer of the lesioned hippocampus. These results demonstrate that in the neonatal brain, acute excitotoxic injury stimulates expression of both MCP-1 and its receptor, CCR2, and suggests that MCP-1 regulates the microglial/monocyte response to acute brain injury.
Galasso
J M
JM
Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48109-0646, USA.
Miller
M J
MJ
Cowell
R M
RM
Harrison
J K
JK
Warren
J S
JS
Silverstein
F S
FS
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000187:drug effects* / Q000378:metabolism
C515336:Ccr2 protein, rat; D018932:Chemokine CCL2; D018690:Excitatory Amino Acid Agonists; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D016202:N-Methylaspartate