MISC

2005年3月

Calpain inhibitors prevent neuronal cell death and ameliorate motor disturbances after compression-induced spinal cord injury in rats

JOURNAL OF NEUROTRAUMA
  • S Arataki
  • ,
  • K Tomizawa
  • ,
  • A Moriwaki
  • ,
  • K Nishida
  • ,
  • M Matsushita
  • ,
  • T Ozaki
  • ,
  • T Kunisada
  • ,
  • A Yoshida
  • ,
  • H Inoue
  • ,
  • H Matsui

22
3
開始ページ
398
終了ページ
406
記述言語
英語
掲載種別
DOI
10.1089/neu.2005.22.398
出版者・発行元
MARY ANN LIEBERT INC

Traumatic spinal cord injury (SCI) results in widespread neuronal cell death. Recent studies have suggested that activated calpain mediates neuronal cell death in the central nervous system. We conducted a study to determine whether calpain mediates neuronal cell death in the motor neurons of the spinal cord after SCI, and whether postinjury administration of the calpain inhibitors N-acetyl-Leu-Leu-Met-CHO (ALLM) and calpain inhibitor III (CI III) (MDL28170) reduces the motor disturbances in rats with a model of SCI. Adult male Wistar rats were subjected to SCI by application of a 20-g weight impactor probe to the spinal cord at T12 for 20 min. The rats were divided into three groups according to whether they were injected intravenously with 0.05-2.5 mg/kg ALLM, 10 mg/kg CI III, or 0.1% DMSO as a control every 24 h for I week after SCI. Calpain was activated in the spinal cord at 8 h, 24 h, and 5 days after SCI, and administration of ALLM inhibited its activation. ALLM, as compared to the DMSO vehicle alone, also significantly reduced the number of motor neurons in spinal-cord lesions that were positively labeled at 24 h after SCI with the terminal deoxynucleotidyl transferase-uridine nucleotide end-labeling (TUNEL) technique. Additionally, both the inclined plane test and footprint analysis showed markedly better motor activity after 4 weeks in rats injected with ALLM or CI III than in rats given vehicle only. These results suggest that activation of calpain plays a critical role in the neuronal cell death that follows SCI, and that calpain inhibitors may have benefit in treating the motor disturbances that follow SCI.

リンク情報
DOI
https://doi.org/10.1089/neu.2005.22.398
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000228019500006&DestApp=WOS_CPL
ID情報
  • DOI : 10.1089/neu.2005.22.398
  • ISSN : 0897-7151
  • Web of Science ID : WOS:000228019500006

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