Neurodegeneration in the rat hippocampus and striatum after middle cerebral artery occlusion.
Animal models of ischemia are in wide use to elucidate the molecular mechanisms of brain injury that result from cardiovascular disease in humans. We have used the fluorescent, anionic dye, Fluoro-Jade, to examine cellular degeneration that occurs in association with the middle cerebral artery occlusion (MCAO) model. MCAO results in cortical infarction as well as damage to the hippocampus leading to a delayed form of death of hippocampal neurons. We examined brain sections at 6 h, 12 h, 1, 4, 7, 14 and 21 days after injury. Fluoro-Jade labeling of the striatum was seen over a protracted time-course, with degeneration beginning by 6 h after injury. Neuronal degeneration in the hippocampus, in contrast, occurs between 12 h and 7 days after injury with neuronal death reaching a peak at 4 days. GFAP/Fluoro-Jade double labeling revealed that the Fluoro-Jade positive staining at late time-points in the striatum included astrocytic cells. Together, the results show Fluoro-Jade to be a useful marker of cellular degeneration following ischemic injury. Further, the use of this dye has enabled us to demonstrate previously undescribed events of cellular injury resulting from ischemia.
Butler
Tanya L
TL
Department of Pharmacology, University of South Florida, Tampa, FL 33612, USA.
Kassed
Cheryl A
CA
Sanberg
Paul R
PR
Willing
Alison E
AE
Pennypacker
Keith R
KR
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002536:Cerebral Arteries; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D009410:Nerve Degeneration / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D009930:Organic Chemicals; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005452:Fluoresceins; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D009930:Organic Chemicals; C435731:fluoro jade