Comparative neuroprotective effect of sodium channel blockers after experimental spinal cord injury.
Spinal cord injury (SCI) results in loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Influx of Na(+) ions into cells has been postulated to be a key early event in the pathogenesis of secondary traumatic and ischemic central nervous system injury. Previous studies have shown that some voltage-sensitive sodium channel blockers provide powerful neuroprotection. The purpose of the present study was to compare the neuroprotective effect of three sodium channel blockers-mexiletine, phenytoin and riluzole--after SCI. Ninety rats were randomly and blindly divided into five groups of 18 rats each: sham-operated group, trauma group (bolus injection of 1 mL physiological saline intraperiteonally [i.p.]), mexiletine treatment group (80 mg/kg, i.p.), phenytoin treatment group (200 mg/kg, i.p.) and riluzole treatment group (8 mg/kg, i.p.). Twenty-four hours after injury, the rats were killed for determination of spinal cord water content and malondialdehyde (MDA) levels. Motor function scores of six rats from each group were evaluated weekly for six weeks. Then the rats were killed for histopathological assessment. Although all the treatment groups revealed significantly lower MDA levels and spinal cord edema than the trauma group (p<0.05), the riluzole and mexiletine treatment groups were better than the phenytoin treatment group. In the chronic stage, riluzole and mexiletine treatment achieved better results for neurobehavioral and histopathological recovery than phenytoin treatment. In conclusion, all the tested Na(+) blockers had a neuroprotective effect after SCI; riluzole and mexiletine were superior to phenytoin.
Ates
Ozkan
O
Inonu University, School of Medicine, Department of Neurosurgery, Turgut Ozal Medical Center, 44069 Malatya, Turkey. atesozkan@hotmail.com
Cayli
Suleyman R
SR
Gurses
Ilal
I
Turkoz
Yusuf
Y
Tarim
Ozcan
O
Cakir
Celal O
CO
Kocak
Ayhan
A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D015227:Lipid Peroxidation / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008801:Mexiletine / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D010672:Phenytoin / Q000627:therapeutic use; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019782:Riluzole / Q000627:therapeutic use; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018709:Statistics, Nonparametric; D013997:Time Factors; D014867:Water / Q000378:metabolism
D026941:Sodium Channel Blockers; D014867:Water; D008801:Mexiletine; D010672:Phenytoin; D019782:Riluzole