Calpain inhibition reduces axolemmal leakage in traumatic axonal injury

Czeiter, Endre (author): Department of Neurosurgery, University of Pécs, Pécs, Hungary

Büki, Andras, 1966- (author): Department of Neurosurgery, University of Pécs, Pécs, Hungary

Bukovics, Péter (author): Department of Neurosurgery, University of Pécs, Pécs, Hungary

Farkas, Orsolya (author): Department of Neurosurgery, University of Pécs, Pécs, Hungary

Pál, József (author): Department of Neurosurgery, University of Pécs, Pécs, Hungary

Kövesdi, Erzsébet (author): Department of Neurosurgery, University of Pécs, Pécs, Hungary

Dóczi, Tamás (author): Department of Neurosurgery, University of Pécs, Pécs, Hungary

Sándor, János (author): Department of Public Health, Institute of Applied Health Sciences, University of Pécs, Pécs, Hungary

(creator_code:org_t)

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Abstract Subject headings

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.

By the author/editor: Czeiter, Endre; Büki, Andras, 19 ...; Bukovics, Péter; Farkas, Orsolya; Pál, József; Kövesdi, Erzsébe ...; show more...; Dóczi, Tamás; Sándor, János; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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