Postischemic hyperthermia induces Alzheimer-like pathology in the rat brain.
This study addresses the effects of induced hyperthermia on post-ischemic rat brain evaluated histologically and/or immunohistochemically after 7-day, 2-month or 6-month survival. Hyperthermia (38.5 degrees - 40 degrees C) maintained (by heating the cage environment to 34-35 degrees C) for two consecutive periods of 5 and 9 h timed, respectively, from 4- and 21-h recirculation following 10-min global ischemia (two-vessel occlusion + hypotension) induced chronic neuronal death that became apparent in the rat forebrain from 7-day to 2-month survival. Associated immunohistochemical findings after 2 or 6 months of recovery included: (1) complement activation (membrane attack complex formation); (2) generalized overexpression of ubiquitin in surviving forebrain neurons; (3) persistent activation of macrophages; (4) presence of gemistocytic astrocytes in the hippocampus; (5) maturation of amyloid plaques (identified by immunohistochemistry using anti-human beta-A4 primary antibody) in cerebral cortex; and (6) intracellular deposits identified by anti-human hyperphosphorylated tau protein antibodies. This novel non-transgenic, self-sustained model of neurodegeneration triggered by the association of two prevalent insults to the aging human brain (ischemia and hyperthermia) presents morphological features similar to those of Alzheimer's disease. This finding raises the possibility that febrile complications of acute brain injuries may similarly impair human cognitive function in the long run.
Sinigaglia-Coimbra
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R
Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil.
Cavalheiro
E A
EA
Coimbra
C G
CG
D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001831:Body Temperature / Q000502:physiology; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D004195:Disease Models, Animal; D005334:Fever / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006979:Hyperthermia, Induced; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D015704:CD4 Antigens; D016827:CD8 Antigens; D015938:Complement Membrane Attack Complex; D000949:Histocompatibility Antigens Class II; D014409:Tumor Necrosis Factor-alpha; D025801:Ubiquitin; D016875:tau Proteins