Alterations in tau immunostaining in the rat hippocampus following transient cerebral ischemia.
Previous studies in gerbils have shown that cytoskeletal disruption and a loss of the dendritic microtubule-associated protein, MAP2, may occur after short periods of transient global ischemia. tau, a predominantly axonal microtubule-associated protein, has not been examined following ischemia. We compared neuronal damage with alterations in MAP2, tau, and 72-kD heat shock protein (HSP72) immunostaining at various reperfusion times following 20 min of ischemia in the rat four-vessel occlusion model. tau accumulated in neuronal cell bodies throughout the hippocampal formation 30 min to 2 h after the ischemic insult. Perikaryal tau immunostaining was transient in most regions, but persisted in polymorphic hilar neurons. This was accompanied by a loss of immunostaining in the target of many hilar neurons, the inner molecular layer of the dentate gyrus. The same neuronal populations that exhibited increased tau immunostaining of perikarya later displayed an induction of HSP72 immunoreactivity. In contrast, loss of MAP2 immunostaining was not consistently observed before neuronal death and did not correspond to HSP72 induction. The altered tau immunostaining is not the direct result of excitotoxic insult, as intrahippocampal injection of kainic acid did not cause the somal accumulation of tau, but did cause disruption of MAP2 immunostaining. Taken together, the results suggest that the somal accumulation of tau is an early, sensitive, and selective marker of ischemic insult.
Geddes
J W
JW
Sanders-Brown Center on Aging, University of Kentucky, College of Medicine, Lexington 40536-0230.
Schwab
C
C
Craddock
S
S
Wilson
J L
JL
Pettigrew
L C
LC
D000818:Animals; D048588:Benzoxazines; D004396:Coloring Agents; D006360:Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010078:Oxazines; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D016875:tau Proteins / Q000378:metabolism*
D048588:Benzoxazines; D004396:Coloring Agents; D006360:Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; D010078:Oxazines; D016875:tau Proteins; C028911:cresyl violet; D007608:Kainic Acid