title: Increased apoptotic neuronal cell death and cognitive impairment at early phase after traumatic brain injury in aged rats.
abstract: Progressive age-associated increases in cerebral dysfunction have been shown to occur following traumatic brain injury (TBI). Moreover, levels of neuronal mitochondrial antioxidant enzymes in the aged brain are reduced, resulting in free radical-induced cell death. It was hypothesized that cognitive impairment after TBI in the aged progresses to a greater degree than in younger individuals, and that damage involves neuronal degeneration and death by free radicals. In this study, we investigated the effects of free radicals on neuronal degeneration, cell death, and cognitive impairment in 10-week-old (young group) and 24-month-old rats (aged group) subjected to TBI. Young and aged rats received TBI with a pneumatic controlled injury device. At 1, 3 and 7 days after TBI, immunohistochemistry, lipid peroxidation and behavioral studies were performed. At 1, 3 and 7 days post-TBI, the number of 8-hydroxy-2'-deoxyguanosine-, 4-hydroxy-2-nonenal- and single-stranded DNA (ssDNA)-positive cells, and the levels of malondialdehyde around the damaged area after TBI significantly increased in the aged group when compared with the young group (P < 0.05). In addition, the majority of ssDNA-positive cells in both groups co-localized with neuronal cells around the damaged area. There was a significant decrease in the number of surviving neurons and an increase in cognitive impairment after TBI in the aged group when compared with the young group (P < 0.05). These results indicate that following TBI, high levels of free radicals are produced in the aged rat brain, which induces neuronal degeneration and apoptotic cell death around the damaged area, resulting in cognitive impairment.
authors.affiliation: Department of Pathology, Faculty of Medicine, Kinki University, 377-2 Ohno-higashi, Osakasayama, Osaka 589-8511, Japan. tatsuki@med.kindai.ac.jp
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Itoh
authors.forename: Motohiro
authors.initials: M
authors.lastname: Imano
authors.forename: Shozo
authors.initials: S
authors.lastname: Nishida
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsubaki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizuguchi
authors.forename: Shigeo
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ito
authors.forename: Takao
authors.initials: T
authors.lastname: Satou
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000367:Age Factors; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D017209:Apoptosis; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D053904:DNA Breaks, Single-Stranded; D004277:DNA, Single-Stranded / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D000447:Aldehydes; D034961:Antigens, Nuclear; D004277:DNA, Single-Stranded; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal