title: 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.
authors.affiliation: Department of Spine Surgery and Traumatology, Guanghua Integrative Medicine Hospital, Shanghai 200052, China ; Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai 200052, China.
authors.forename: Zifeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Spine Surgery and Traumatology, Guanghua Integrative Medicine Hospital, Shanghai 200052, China ; Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai 200052, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Spine Surgery and Traumatology, Guanghua Integrative Medicine Hospital, Shanghai 200052, China ; Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai 200052, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of Spine Surgery and Traumatology, Guanghua Integrative Medicine Hospital, Shanghai 200052, China ; Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai 200052, China.
authors.forename: Licheng
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Spine Surgery and Traumatology, Guanghua Integrative Medicine Hospital, Shanghai 200052, China ; Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai 200052, China.
authors.forename: Songtao
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Spine Surgery and Traumatology, Guanghua Integrative Medicine Hospital, Shanghai 200052, China ; Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai 200052, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000208:Acute Disease; D000818:Animals; D002154:Calpain / Q000378:metabolism*; D006023:Glycoproteins / Q000008:administration & dosage*; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: C568306:(3-ethoxycarbonyloxirane-2-carbonyl)leucine (3-methylbutyl) amide; D006023:Glycoproteins; C039304:calpain inhibitors; D002154:Calpain; C000606071:Capn1 protein, rat; D007930:Leucine