PMID- 15785234
OWN - NLM
STAT- MEDLINE
DCOM- 20050602
LR  - 20061115
IS  - 0897-7151 (Print)
IS  - 0897-7151 (Linking)
VI  - 22
IP  - 3
DP  - 2005 Mar
TI  - Calpain inhibitors prevent neuronal cell death and ameliorate motor disturbances 
      after compression-induced spinal cord injury in rats.
PG  - 398-406
AB  - 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.
FAU - Arataki, Shinya
AU  - Arataki S
AD  - Department of Physiology, Okayama University Graduate School of Medicine and 
      Dentistry, Okayama, Japan.
FAU - Tomizawa, Kazuhito
AU  - Tomizawa K
FAU - Moriwaki, Akiyoshi
AU  - Moriwaki A
FAU - Nishida, Keiichirou
AU  - Nishida K
FAU - Matsushita, Masayuki
AU  - Matsushita M
FAU - Ozaki, Toshifumi
AU  - Ozaki T
FAU - Kunisada, Toshiyuki
AU  - Kunisada T
FAU - Yoshida, Aki
AU  - Yoshida A
FAU - Inoue, Hajime
AU  - Inoue H
FAU - Matsui, Hideki
AU  - Matsui H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (Glycoproteins)
RN  - 0 (calpain inhibitors)
RN  - EC 3.4.22.- (Calpain)
SB  - IM
MH  - Animals
MH  - Calpain/*antagonists & inhibitors/metabolism
MH  - Cell Death/drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Glycoproteins/*pharmacology/therapeutic use
MH  - Male
MH  - Motor Skills Disorders/*drug therapy/enzymology
MH  - Neurons/*drug effects/enzymology
MH  - Rats
MH  - Rats, Wistar
MH  - Spinal Cord Injuries/*drug therapy/enzymology
MH  - Thoracic Vertebrae
EDAT- 2005/03/24 09:00
MHDA- 2005/06/03 09:00
CRDT- 2005/03/24 09:00
PHST- 2005/03/24 09:00 [pubmed]
PHST- 2005/06/03 09:00 [medline]
PHST- 2005/03/24 09:00 [entrez]
AID - 10.1089/neu.2005.22.398 [doi]
PST - ppublish
SO  - J Neurotrauma. 2005 Mar;22(3):398-406. doi: 10.1089/neu.2005.22.398.