Attenuation of microtubule associated protein-2 degradation after mild head injury by mexiletine and calpain-2 inhibitor

• Published in: British journal of neurosurgery 2007-06, Vol.21 (3), p.281-287
• Main Authors: Atalay, B., Caner, H., Can, A., Cekinmez, M.
• Format: Article
• Language: English
• Subjects: Animals; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain damage; Calpain - antagonists & inhibitors; Calpain inhibitor; Cytoskeleton - drug effects; Disease Models, Animal; Head Injuries, Closed - metabolism; Head Injuries, Closed - pathology; Immunologic Techniques; Inhibitor drugs; Injections, Intraperitoneal; Leupeptins - pharmacology; Lipid Peroxidation - drug effects; Male; mexiletine; Mexiletine - pharmacology; microtubule associated protein-2; Microtubule-Associated Proteins - analysis; Microtubule-Associated Proteins - drug effects; Microtubule-Associated Proteins - metabolism; mild head trauma; Neurology; Neurons; Protease Inhibitors - pharmacology; Proteins; Rats; Rats, Sprague-Dawley; Rodents; Time Factors
• ISSN: 0268-8697; 1360-046X
• DOI: 10.1080/02688690701364781

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.