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

Shinya Arataki, Kazuhito Tomizawa, Akiyoshi Moriwaki, Keiichiro Nishida, Masayuki Matsushita, Toshihumi Ozaki, Toshiyuki Kunisada, Aki Yoshida, Hajime Inoue, Hideki Matsui

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 SCL 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.

Original languageEnglish
Pages (from-to)398-406
Number of pages9
JournalJournal of Neurotrauma
Volume22
Issue number3
DOIs
Publication statusPublished - Mar 2005

Fingerprint

Spinal Cord Injuries
Cell Death
Calpain
Spinal Cord
Motor Neurons
Dimethyl Sulfoxide
Uracil Nucleotides
DNA Nucleotidylexotransferase
calpain inhibitors
Wistar Rats
Motor Activity
Central Nervous System
Weights and Measures
calpain inhibitor III

Keywords

  • Apoptosis
  • Motor neuron
  • SCI
  • Spinal cord
  • Terminal deoxynucleotidyl transferase-uridine nucleotide end-labeling technique

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Calpain inhibitors prevent neuronal cell death and ameliorate motor disturbances after compression-induced spinal cord injury in rats. / Arataki, Shinya; Tomizawa, Kazuhito; Moriwaki, Akiyoshi; Nishida, Keiichiro; Matsushita, Masayuki; Ozaki, Toshihumi; Kunisada, Toshiyuki; Yoshida, Aki; Inoue, Hajime; Matsui, Hideki.

In: Journal of Neurotrauma, Vol. 22, No. 3, 03.2005, p. 398-406.

Research output: Contribution to journalArticle

Arataki, Shinya ; Tomizawa, Kazuhito ; Moriwaki, Akiyoshi ; Nishida, Keiichiro ; Matsushita, Masayuki ; Ozaki, Toshihumi ; Kunisada, Toshiyuki ; Yoshida, Aki ; Inoue, Hajime ; Matsui, Hideki. / Calpain inhibitors prevent neuronal cell death and ameliorate motor disturbances after compression-induced spinal cord injury in rats. In: Journal of Neurotrauma. 2005 ; Vol. 22, No. 3. pp. 398-406.
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