Neuroprotective Effects of Kangen-karyu on Spatial Memory Impairment in an 8-Arm Radial Maze and Neuronal Death in the Hippocampal CA1 Region Induced by Repeated Cerebral Ischemia in Rats

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  • Pu Fengling
    Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
  • Motohashi Kyoko
    Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
  • Kaneko Tomohiro
    Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
  • Tanaka Yurika
    Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
  • Manome Naomi
    Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
  • Irie Keiichi
    Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan Advanced Materials Institute, Fukuoka University, Japan
  • Takata Jirou
    Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
  • Egashira Nobuaki
    Department of Pharmacy, Kyushu University Hospital, Japan
  • Oishi Ryozo
    Department of Pharmacy, Kyushu University Hospital, Japan
  • Okamoto Takuya
    Iskra Industry Co., Ltd., Japan
  • Sei Yasuo
    Iskra Industry Co., Ltd., Japan
  • Yokozawa Takako
    Institute of Natural Medicine, University of Toyama, Japan
  • Mishima Kenichi
    Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan Advanced Materials Institute, Fukuoka University, Japan
  • Iwasaki Katsunori
    Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan Advanced Materials Institute, Fukuoka University, Japan
  • Fujiwara Michihiro
    Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan

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Abstract

In the present study, we investigated the neuroprotective effects of Kangen-karyu (KGK) in a repeated cerebral ischemia model (2 × 10 min, 1-h interval). A 21-day pre- and post-ischemic treatment with KGK (10 – 300 mg/kg) and aspirin (5 mg/kg) improved the spatial memory impairment and neuronal death in the hippocampal CA1 region induced by repeated cerebral ischemia. However, a 7-day post-ischemic treatment with KGK did not attenuate the spatial memory impairment and neuronal death in this model. To determine the mechanism of action of KGK, we investigated the effects of a 14-day pre-ischemic treatment with KGK on cerebral blood flow in the hippocampal area of the repeated cerebral ischemia model using laser Doppler flowmetry. The 14-day pre-ischemic treatment with KGK increased the cerebral blood flow during reperfusion. These results suggest that a 21-day pre- and post-ischemic treatment with KGK can protect against brain damage caused by cerebral ischemia by increasing the cerebral blood flow in the hippocampal area.<br>

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