Journal
STROKE
Volume 33, Issue 3, Pages 795-801Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/hs0302.103740
Keywords
astrocytes; chemokines; endothelium; neonate; receptors, chemokine; rats
Categories
Funding
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS031054] Funding Source: NIH RePORTER
- NINDS NIH HHS [NS31054] Funding Source: Medline
- PHS HHS [35059] Funding Source: Medline
Ask authors/readers for more resources
Background and Purpose-Macrophage inflammatory protein (MIP)-1alpha is a well-characterized monocyte chemoattractant; its role in regulating monocyte and microglial recruitment and activation in the injured neonatal brain is unknown. We evaluated the impact of acute hypoxic-ischemic (HI) brain injury on the expression of MIP-1alpha in neonatal rat brain. Methods-To elicit forebrain ischemic injury, 7-day-old (P7) rats underwent right carotid ligation, followed by 2.5 hours of 8% oxygen exposure. We used an enzyme-linked immunosorbent assay and immunohistochemistry to detect MIP-1alpha; double-labeling immunofluorescence assays were analyzed with confocal microscopy to identify cellular sources of MIP-1alpha. Immunocytochemistry assays were also used to detect 2 MIR-1alpha receptors, CCR1 and CCR5. Results-We found marked increases in tissue concentrations of MIP-1alpha in the HI cerebral hemisphere, peaking from 8 to 72 hours after lesioning. Immunocytochemistry assays revealed that MIP-1alpha was constitutively expressed in physiologically activated microglia; from 8 to 120 hours after lesioning, MIP-1alpha immunoreactive monocytes and microglia accumulated in the lesion territory. In immunoreactive cells, MIP-1alpha was diffusely distributed throughout the cytoplasm at early post-HI time intervals; by 72 hours, MIP-1alpha immunoreactivity was typically concentrated adjacent to the nucleus, a pattern indicative of active MIP-1alpha production. In P7 to P12 brain, many cells expressed MIP-1alpha receptors; both CCR1 and CCR5 immunoreactivity were localized to endothelium and ependyma; CCR1-immunoreactive astrocytes and neurons and CCR5-immunoreactive microglia were also identified. Conclusions-These data implicate MIP-1alpha as a mediator of the complex and sustained inflammatory response initiated by perinatal HI brain injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available