Hypoxic-Ischemic Injury Induces Monocyte Chemoattractant Protein-1 Expression in Neonatal Rat Brain

Abstract

Monocyte chemoattractant protein-1 (MCP-1) regulates monocyte accumulation in several macrophage-dependent experimental disease models. In the neonatal brain, activated microglia accumulate rapidly after hypoxic-ischemic injury. These cells produce potentially neurotoxic factors that may contribute to the progression of injury. To determine whether MCP-1 could be one of the molecular signals that influences the microglial response to hypoxic-ischemic injury in the neonatal brain, we examined the impact of acute hypoxic-ischemic injury on MCP-1 mRNA and protein expression. Seven-day-old rats underwent right carotid artery ligation, followed by 3 hours of 8% oxygen exposure, to elicit ipsilateral forebrain hypoxic-ischemic injury. To detect MCP-1 mRNA in situ hybridization assays were performed using 35S-labeled antisense riboprobes generated from rat MCP-1 cDNA. Animals were evaluated 0, 1, 2, 4, 8, 16, 24, 48, and 120 hours after hypoxic exposure (N > or = 3/group). Immunocytochemistry (with a polyclonal rabbit antirat MCP-1 antibody) was used to determine the anatomic and temporal distribution of MCP-1, in samples obtained 10 minutes to 5 days after hypoxic exposure (N > or = 3/group). Monocyte chemoattractant protein-1 mRNA was first detected in periventricular regions of the lesioned hemisphere 1 hour after hypoxia-ischemia; periependymal and intraparenchymal MCP-1 mRNA expression were detected at 4 hours; hybridization signal peaked at 8 to 24 hours; and no MCP-1 mRNA was detected at 48 and 120 hours. In lesioned forebrain, MCP-1 protein expression were consistently detected at 2.5 to 48 hours after hypoxia-ischemia. Many immunoreactive cells appeared to be neurons. These results suggest that in the developing brain, MCP-1 could represent a functionally important molecular signal for the microglial response to hypoxic-ischemic injury.

Staphylococcus epidermidisBacteremia Induces Brain Injury in Neonatal Mice via Toll-like Receptor 2-Dependent and -Independent Pathways

“…However, with respect to cytokines and chemokines in brain homogenates, S. epidermidis injection increased concentrations of CCL2 but not the other chemokines/cytokines examined. CCL2 is rapidly upregulated in response to a variety of acute and chronic CNS disorders [32], including neonatal brain injury in rodent models [33] and human infants [34]. CCL2 is released across the apical and basolateral membranes of the choroid epithelium and can mediate leukocyte recruitment to the choroid plexus [35,36].…”

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

“…Hypoxia has been reported to upregulate MCP-1 expression in human dermal fibroblasts, 40 neonatal rat brain 41 and melanona cells. 42 The formation of MCP-1 is reduced by hypoxia in ovarian cancer cells, 43 macrophages 44,45 and human synovial fibroblasts.…”

The origin and differentiation of microglial cells during development

“…These factors are produced by brain macrophages/microglial cells, which therefore contribute to the recruitment of cells of the same type, and also by nonmicroglial cells (Ransoho et al, 1993;Mallat et al, 1996). It has been demonstrated that some of these factors are also released in the immature brain after injury (Ivacko et al, 1997), but at the moment we do not know if they in¯uence the migration of microglial cells in the developing normal brain.…”

“…However, little is known about the relationship between cell death and microglial invasion. Both disease and injury of the CNS in rats and mice induces the expression of genes that code for a monocyte/macrophage chemoattractant factor, monocyte chemoattractant protein-1 (MCP-1) (Glabinski et al, 1996;Ivacko et al, 1997); this or similar chemoattractants are likely involved in the recruitment of mononuclear phagocytes from the blood stream, and perhaps also from the surrounding nervous parenchyma (see Section 4.2.2). However, it is not known whether these factors released during the process of cell degeneration come into play during development.…”