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Therapeutic Efficacy of E-64-d, a Selective Calpain Inhibitor, in Experimental Acute Spinal Cord Injury.

Abstract
This study aims to investigate the therapeutic effect of calpain inhibitor E-64-d on SCI and to find a new approach to treat SCI. When an SCI rat model was established, it was immediately administered with E-64-d. RT-PCR and Western blotting were used to determine the protein and mRNA levels of calpain 1 and 68-kD NFP. TUNEL staining and NeuN labeling were performed to analyze neuronal apoptosis in the lesion. Immunohistochemistry assay was carried out to observe the expressions of calpain 1 and GFAP. Cyclooxygenase-2 activity was measured to show the immune response status. Locomotor function was evaluated by inclined plane test and Basso, Beattie, and Bresnahan locomotor rating scale. The results showed that calpain 1 was activated after SCI occurred. Treatment with E-64-d decreased expressions of calpain 1 and GFAP, alleviated neuronal apoptosis, inhibited cyclooxygenase-2 activity, and resulted in the promoted locomotor function. Furthermore, combination of E-64-d and MP had better efficacy than did E-64-d or MP alone. E-64-d is expected to be applied to treat SCI, and its alliance with MP may provide a valid strategy for SCI therapy.
AuthorsZifeng Zhang, Zheng Huang, Hao Dai, Licheng Wei, Songtao Sun, Feng Gao
JournalBioMed research international (Biomed Res Int) Vol. 2015 Pg. 134242 ( 2015) ISSN: 2314-6141 [Electronic] United States
PMID26240815 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • (3-ethoxycarbonyloxirane-2-carbonyl)leucine (3-methylbutyl) amide
  • Glycoproteins
  • calpain inhibitors
  • Calpain
  • Capn1 protein, rat
  • Leucine
Topics
  • Acute Disease
  • Animals
  • Calpain (metabolism)
  • Glycoproteins (administration & dosage)
  • Leucine (administration & dosage, analogs & derivatives)
  • Locomotion (drug effects)
  • Male
  • Rats
  • Recovery of Function (drug effects)
  • Spinal Cord Injuries (diagnosis, drug therapy, physiopathology)
  • Treatment Outcome

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