title: Calpain inhibition reduces axolemmal leakage in traumatic axonal injury.
abstract: Calcium-induced, calpain-mediated proteolysis (CMSP) has recently been implicated to the pathogenesis of diffuse (traumatic) axonal injury (TAI). Some studies suggested that subaxolemmal CMSP may contribute to axolemmal permeability (AP) alterations observed in TAI. Seeking direct evidence for this premise we investigated whether subaxolemmal CMSP may contribute to axolemmal permeability alterations (APA) and pre-injury calpain-inhibition could reduce AP in a rat model of TAI. Horseradish peroxidase (HRP, a tracer that accumulates in axons with APA) was administered one hour prior to injury into the lateral ventricle; 30 min preinjury a single tail vein bolus injection of 30 mg/kg MDL-28170 (a calpain inhibitor) or its vehicle was applied in Wistar rats exposed to impact acceleration brain injury. Histological detection of traumatically injured axonal segments accumulating HRP and statistical analysis revealed that pre-injury administration of the calpain inhibitor MDL-28170 significantly reduced the average length of HRP-labeled axonal segments. The axono-protective effect of pre-injury calpain inhibition recently demonstrated with classical immunohistochemical markers of TAI was further corroborated in this experiment; significant reduction of the length of labeled axons in the drug-treated rats implicate CMSP in the progression of altered AP in TAI.
authors.affiliation: Department of Neurosurgery, University of Pécs, Pécs, Hungary. endre.czeiter@aok.pte.hu
authors.forename: Endre
authors.initials: E
authors.lastname: Czeiter
authors.forename: András
authors.initials: A
authors.lastname: Büki
authors.forename: Péter
authors.initials: P
authors.lastname: Bukovics
authors.forename: Orsolya
authors.initials: O
authors.lastname: Farkas
authors.forename: József
authors.initials: J
authors.lastname: Pál
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Kövesdi
authors.forename: Tamás
authors.initials: T
authors.lastname: Dóczi
authors.forename: János
authors.initials: J
authors.lastname: Sándor
mesh_terms: D000818:Animals; D001369:Axons; D002154:Calpain / Q000037:antagonists & inhibitors*; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D002154:Calpain; C058076:calpain inhibitor III