Abstract |
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 1 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.
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Authors | Shinya Arataki, Kazuhito Tomizawa, Akiyoshi Moriwaki, Keiichirou Nishida, Masayuki Matsushita, Toshifumi Ozaki, Toshiyuki Kunisada, Aki Yoshida, Hajime Inoue, Hideki Matsui |
Journal | Journal of neurotrauma
(J Neurotrauma)
Vol. 22
Issue 3
Pg. 398-406
(Mar 2005)
ISSN: 0897-7151 [Print] United States |
PMID | 15785234
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Glycoproteins
- calpain inhibitors
- Calpain
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Topics |
- Animals
- Calpain
(antagonists & inhibitors, metabolism)
- Cell Death
(drug effects, physiology)
- Dose-Response Relationship, Drug
- Glycoproteins
(pharmacology, therapeutic use)
- Male
- Motor Skills Disorders
(drug therapy, enzymology)
- Neurons
(drug effects, enzymology)
- Rats
- Rats, Wistar
- Spinal Cord Injuries
(drug therapy, enzymology)
- Thoracic Vertebrae
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