Enhanced hippocampal neurodegeneration after traumatic or kainate excitotoxicity in GFAP-null mice.
Astrocytes perform a variety of functions in the adult central nervous system. Recent evidence suggests that the upregulation of glial fibrillary acidic protein (GFAP), an astrocyte-specific intermediate filament component, is a biological marker of neurotoxicity after cerebral injury. We herein compared the response to traumatic brain injury or kainic acid (KA)-induced neurotoxicity in GFAP knockout (GFAP-KO) and wild-type (WT) mice. Seventy-two hours after injury, all GFAP-KO mice showed hippocampal CA3 neurodegeneration, whereas WT mice did not show neurodegeneration. Seventy-two hours after KA administration, GFAP-KO mice were more susceptible to KA-induced seizures and had an increased number of pyknotic damaged CA3 neurons than did WT mice. These results indicate that GFAP plays a crucial role in pyramidal neuronal survival after injury or KA-induced neurotoxicity.
Otani
Naoki
N
Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. gra006@ad.ndmc.ac.jp
Nawashiro
Hiroshi
H
Fukui
Shinji
S
Ooigawa
Hidetoshi
H
Ohsumi
Atsushi
A
Toyooka
Terushige
T
Shima
Katsuji
K
Gomi
Hiroshi
H
Brenner
Michael
M
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D002450:Cell Communication / Q000235:genetics; D002470:Cell Survival / Q000502:physiology; D019610:Cytoprotection / Q000235:genetics*; D004195:Disease Models, Animal; D004351:Drug Resistance / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D020127:Recovery of Function / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D005904:Glial Fibrillary Acidic Protein; D009498:Neurotoxins; D007608:Kainic Acid