Increased immunolocalization of nitric oxide synthases during blood-brain barrier breakdown and cerebral edema.
The role of nitric oxide (NO) in blood-brain barrier (BBB) breakdown and edema formation was investigated in the rat cortical cold injury model over a period of 10 min to 6 days post cold-injury by immunolocalization of fibronectin as a marker of BBB permeability alterations and endothelial (e) and inducible (i) nitric oxide synthases (NOS), which are markers of NO biosynthetic activity. BBB breakdown to fibronectin in lesion vessels was observed at 10 minutes post-injury, was maximal between 60 minutes and 3 hours and declined gradually thereafter, while perilesional vessels remained permeable up to 5 days. Increased eNOS immunoreactivity was observed in endothelium of perilesional permeable vessels starting at 12 hrs and was maximal between 4-6 days, after which immunoreactivity decreased reaching basal levels by 5-6 days. Immunoreactivity for iNOS was absent in normal brain and was first observed in polymorphonuclear leukocytes and endothelium of lesion vessels at 3 hrs. Maximal iNOS immunoreactivity was observed in endothelial cells and macrophages during the period of angiogenesis. Smooth muscle cells of overlying hyperplastic pial vessels showed iNOS immunoreactivity up to 6 days. The demonstration of increased NO synthases at the lesion site during BBB breakdown and edema formation and angiogenesis suggests that NO plays a role in these processes.
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Department of Pathology (Neuropathology), Toronto Western Research Institute, Toronto, Canada.
Picard
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Stewart
D J
DJ
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001929:Brain Edema / Q000473:pathology*; D002199:Capillary Permeability / Q000502:physiology; D002540:Cerebral Cortex / Q000293:injuries* / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000473:pathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D019001:Nitric Oxide Synthase