title: Temporal progression of kainic acid induced changes in vascular laminin expression in rat brain with neuronal and glial correlates.
abstract: We recently demonstrated a dramatic up regulation of laminin expression within the blood vessels of brain regions vulnerable to excitotoxin mediated neuronal degeneration. Although this effect was clearly demonstrable at 2 days post kainic acid exposure, its expression at shorter and longer post-dosing intervals has not been reported. Therefore, a primary goal of the present study was to characterize the laminin labeling at intervals ranging from 4 hours to 2 months following i.p. injection of kainic acid. To better characterize the nature and possible underlying mechanism of action of the changes in laminin expression, both Fluoro-Jade C and GFAP immunohistochemistry were employed respectively at all survival intervals. At the shortest intervals examined (4hr, 8hr), Fluoro-Jade C positive cells could be detected in the hippocampus, thalamus, and piriform cortex. In these same regions, both vascular laminin and astrocytic GFAP expression were up regulated. At intermediate survival intervals (2, 5, 14, and 21 days), the respective labeling of degenerating neurons, astrocytes and capillaries were all maximal. Morphologically, Fluoro-Jade C labeled degenerating neurons were labeled in their entirety, GFAP positive astrocytes appeared hypertrophic and blood vessels took on a fragmented appearance. Hypertrophied GFAP positive astrocytes were conspicuous around periphery of the lesion but absent within the core of the lesion at these times. At longer survival intervals (1-2 months), the number of FJ-C labeled degenerating neurons was greatly reduced, while GFAP staining essentially returned to base line and laminin expression remained noticeably elevated, although the vessels appeared to be intact morphologically. These data allow for speculation on possible mechanisms underlying these events.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Road, HFT-132, Jefferson, AR 72079, USA. Sumit.Sarkar@FDA.HHS.GOV
authors.forename: Sumit
authors.initials: S
authors.lastname: Sarkar
authors.forename: James
authors.initials: J
authors.lastname: Raymick
authors.forename: Larry
authors.initials: L
authors.lastname: Schmued
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007608:Kainic Acid / Q000633:toxicity*; D007797:Laminin / Q000819:agonists / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology* / Q000503:physiopathology*; D009498:Neurotoxins / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D009498:Neurotoxins; D007608:Kainic Acid