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Increased apoptotic neuronal cell death and cognitive impairment at early phase after traumatic brain injury in aged rats

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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.

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Acknowledgments

The authors thank Mari Yachi for technical assistance.

Conflict of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine, Kinki University, 377-2 Ohno-higashi, Osakasayama, Osaka, 589-8511, Japan

    Tatsuki Itoh, Akihiko Ito & Takao Satou

  2. Department of Surgery, Faculty of Medicine, Kinki University, Osakasayama, Osaka, Japan

    Motohiro Imano

  3. Faculty of Pharmaceutical Sciences, Kinki University, Higashiosaka, Osaka, Japan

    Shozo Nishida & Masahiro Tsubaki

  4. Life Science Research Institute, Kinki University, Osakasayama, Osaka, Japan

    Nobuyuki Mizuguchi

  5. Department of Pathology, PL Hospital, Osaka, Japan

    Shigeo Hashimoto

  6. Division of Hospital Pathology, Faculty of Medicine, Hospital of Kinki University, Osakasayama, Osaka, Japan

    Takao Satou

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  1. Tatsuki Itoh
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  2. Motohiro Imano
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  3. Shozo Nishida
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  8. Takao Satou
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Correspondence to Tatsuki Itoh.

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Itoh, T., Imano, M., Nishida, S. et al. Increased apoptotic neuronal cell death and cognitive impairment at early phase after traumatic brain injury in aged rats. Brain Struct Funct 218, 209–220 (2013). https://doi.org/10.1007/s00429-012-0394-5

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  • DOI: https://doi.org/10.1007/s00429-012-0394-5

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