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Improvement of cerebral function by anti-amyloid precursor protein antibody infusion after traumatic brain injury in rats

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Abstract

We previously demonstrated the increased amyloid precursor protein (APP) immunoreactivity around the site of damage after traumatic brain injury (TBI). However, the function of APP after TBI has not been evaluated. In this study, we investigated the effects of direct infusion of an anti-APP antibody into the damaged brain region on cerebral function and morphological changes following TBI in rats. Three days after TBI, there were many TUNEL-positive neurons and astrocytes around the damaged region and a significantly greater number of TUNEL-positive cells in the PBS group compared with the anti-APP group found. Seven days after TBI, there were significantly a greater number of large glial fibrillary acidic protein-positive cells, long elongated projections, and microtubule-associated protein-2-positive cells around the damaged region in the anti-APP group compared with the PBS group found. Seven days after TBI, the region of brain damage was significantly smaller and the time to arrival at a platform was significantly shorter in the anti-APP group compared with the PBS group. Furthermore, after TBI in the anti-APP group, the time to arrival at the platform recovered to that observed in uninjured sham operation group rats. These data suggest that the overproduction of APP after TBI inhibits astrocyte activity and reduces neural cell survival around the damaged brain region, which speculatively may be related to the induction of Alzheimer disease-type dementia after TBI.

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Acknowledgment

The authors thank Mari Machino and Emi Watanabe for technical assistance.

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Authors and Affiliations

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

    Tatsuki Itoh, Takao Satou & Hiroyuki Ito

  2. Division of Hospital Pathology, Hospital of Kinki University School of Medicine, Osaka, Japan

    Takao Satou

  3. Division of Sports Medicine, Institute of Life Science, Kinki University, Osaka, Japan

    Takao Satou

  4. Kinki University School of Pharmaceutical Sciences, Osaka, Japan

    Shozo Nishida & Masahiro Tsubaki

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

    Shigeo Hashimoto

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  1. Tatsuki Itoh
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  2. Takao Satou
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  3. Shozo Nishida
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  4. Masahiro Tsubaki
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  5. Shigeo Hashimoto
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  6. Hiroyuki Ito
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Correspondence to Tatsuki Itoh.

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Itoh, T., Satou, T., Nishida, S. et al. Improvement of cerebral function by anti-amyloid precursor protein antibody infusion after traumatic brain injury in rats. Mol Cell Biochem 324, 191–199 (2009). https://doi.org/10.1007/s11010-008-0013-1

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  • DOI: https://doi.org/10.1007/s11010-008-0013-1

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