Attenuation of microtubule associated protein-2 degradation after mild head injury by mexiletine and calpain-2 inhibitor.
The objective of the study was to address the early effects of mild, closed, head injuries on neuronal stability and the prevention of microtubule-associated protein-2 (MAP-2) degradation by mexiletine and calpain-2 inhibitor. Twenty-four rats were divided into four groups: control group (1); trauma group without treatment (2); mexiletine-pretreated and subjected to trauma group (3); trauma subjected and then calpain-2 inhibitor received group (4). All animals were subjected to mild, closed, head trauma. Frontal lobes were removed and processed for staining and immunofluorescent labelling of MAP-2 cytoskeletal proteins, which were evaluated by confocal microscopy in serial optical sections showing the three dimensional cytoarchitecture of affected areas. MAP-2 decoration in almost all neurons obtained from traumatized brain regions drastically diminished, while minute filamentous and granular profiles in axons and/or dendrites were retained together implying a massive degradation/depolymerization of microtubules. In contrast, in mexiletine-pretreated animals, MAP-2 positivity in axonal and perikaryonal profiles was fairly retained, which clearly depicts the protective role of mexiletine after trauma. Compared with mexiletine-pretreated group, calpain-2 inhibitor treated group displayed a less well-preserved MAP-2 expression. Mexiletine can prevent cytoskeletal structure and protein degradation after mild head trauma. Calpain-2 inhibitor prevents protein degradation, but cytoskeletal organization is better preserved with mexiletine.
Atalay
B
B
Department of Neurosurgery, Baskent University Faculty of Medicine, Ankara, Turkey. basara@baskent-ank.edu.tr
Caner
H
H
Can
A
A
Cekinmez
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002154:Calpain / Q000037:antagonists & inhibitors*; D003599:Cytoskeleton / Q000187:drug effects; D004195:Disease Models, Animal; D016489:Head Injuries, Closed / Q000378:metabolism* / Q000473:pathology; D007158:Immunologic Techniques; D007274:Injections, Intraperitoneal; D007976:Leupeptins / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D007976:Leupeptins; D008869:Microtubule-Associated Proteins; D011480:Protease Inhibitors; C089487:acetyl-leucinyl-leucinyl-methional; D008801:Mexiletine; D002154:Calpain