Early effects of mild brain trauma on the cytoskeletal proteins neurofilament160 and MAP2, and the preventive effects of mexilitine.
OBJECTIVE
The aims were to investigate the early effects of graded, closed, mild head injury on neurofilament protein (NF160) and microtubule-associated protein-2 (MAP2) and to examine the levels of lipid peroxidation and the impact of mexilitine, inhibitor of lipid peroxidation, pretreatment on tissue damage.


METHODS
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 (50 mg/kg). Groups 2 and 3 were subdivided into subgroups (n = 14 each), which were subjected to 100 g/cm2, 125 g/cm2, 150 g/cm2, and 175 g/cm2 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-NF160 and anti-MAP2 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 NF160 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 MAP2 stainings group 2 animals showed remarkably less MAP2 staining throughout the sections. There were no significant differences in MAP2 staining intensity or pattern among the group 2 subgroups. In contrast, in the sections from the group 3 animals, the level of MAP2 positivity was markedly preserved.


CONCLUSIONS
In conclusion, our results show that the cytoskeletal proteins we investigated have different capacities for resisting injury, and that MAP2 is more vulnerable to injury than NF160. 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 MAP2 and NF160 integrity in closed mild head injury. This protection is inversely proportional to the magnitude of the applied force.
Caner
H
H
Department of Neurosurgery, Baskent University Faculty of Medicine, Ankara, Turkey. hakanc@baskent-ank.edu.tr
Can
A
A
Atalay
B
B
Erdogan
B
B
Albayrak
A H
AH
Kilinc
K
K
Bavbek
M
M
Altinors
N
N
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000032:analysis*; D016489:Head Injuries, Closed / Q000473:pathology*; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D016900:Neurofilament Proteins / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; C061195:neurofilament protein M; D008801:Mexiletine