Early effects of mild brain trauma on the cytoskeletal proteins neurofilament.sub.160 and MAP.sub.2, and the preventive effects of mexilitine

Byline: H. Caner (1), A. Can (2), B. Atalay (1), B. Erdogan (1), A. H. Albayrak (1), K. Kilinc (3), M. Bavbek (1), N. Altinors (1) Keywords: Keywords: Mild head injury; neurofilament protein (NF160); microtubule-associated protein-2 (MAP2); lipid peroxidation mexilitine. Objective. The aims were to... Full description

Byline: H. Caner (1), A. Can (2), B. Atalay (1), B. Erdogan (1), A. H. Albayrak (1), K. Kilinc (3), M. Bavbek (1), N. Altinors (1) Keywords: Keywords: Mild head injury; neurofilament protein (NF160); microtubule-associated protein-2 (MAP2); lipid peroxidation mexilitine. Objective. The aims were to investigate the early effects of graded, closed, mild head injury on neurofilament protein (NF.sub.160) and microtubule-associated protein-2 (MAP.sub.2) and to examine the levels of lipid peroxidation and the impact of mexilitine, inhibitor of lipid peroxidation, pretreatment on tissue damage. Material and method. One hundred and twenty-six rats were divided into groups as follows: Group 1 (n=14) were controls; group 2 (n=56) sustained trauma alone; and group 3 (n=56) were pretreated with mexilitine (50mg/kg). Groups 2 and 3 were subdivided into subgroups (n=14 each), which were subjected to 100g/cm.sup.2, 125g/cm.sup.2, 150g/cm.sup.2, and 175g/cm.sup.2 trauma forces, respectively. Two hours after trauma, the frontal lobes from all groups were removed and processed for lipid peroxidation H&E staining, immunofluorescent labelling of neurofilaments and microtubules with anti-NF.sub.160 and anti-MAP.sub.2 antibodies. Results. Compared to control findings, all the trauma-only animals showed increased lipid peroxidation levels and the elevations paralleled the amount of force applied. Administration of mexilitine significantly reduced the level of lipid peroxidation. In NF.sub.160 stainings, in group 2, the degree of impairment in axonal organization paralleled the different levels of force that were applied. Groups 3C and 3D (mexilitine pretreated) showed well-preserved axons and intact perikarya. In MAP.sub.2 stainings group 2 animals showed remarkably less MAP.sub.2 staining throughout the sections. There were no significant differences in MAP.sub.2 staining intensity or pattern among the group 2 subgroups. In contrast, in the sections from the group 3 animals, the level of MAP.sub.2 positivity was markedly preserved. Conclusion. In conclusion, our results show that the cytoskeletal proteins we investigated have different capacities for resisting injury, and that MAP.sub.2 is more vulnerable to injury than NF.sub.160. One of the reason for this cytoskeletal disruption may be increased lipid peroxidation. Inhibition of lipid peroxidation by pre-treatment with 50-mg/kg mexilitine significantly reduces the level of lipid peroxidation and may protect MAP.sub.2 and NF.