Acamprosate protects rat brain against middle-cerebral-artery-occlusion-induced ischemic injuries through anti-oxidative activities

It is has been reported that acamprosate significantly reduces neurological deficits following transient hemispheric ischemia, which may be related to its antiglutamatergic effect. However, it is unclear whether acamprosate may provide anti-oxidative neuroprotection in cerebral ischemic condition. To investigate the anti-oxidative neuroprotective effects of acamprosate during focal cerebral ischemia, rats were treated with acamprosate through sublingual vein injection 30 min after the onset of MCAO-induced cerebral ischemia. The behavioral tests were performed to evaluate neurological performance. 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to evaluate the infarct area of brain tissue. Spectrophotometric assay was used to determine the activities of superoxide dismutase (SOD) and glutathione-peroxidase (GSH-Px), and contents of malondialdehyde (MDA) and adenosine triphosphate (ATP). Furthermore, the respiratory control ratio (RCR = State 3/State 4) was calculated to determine the brain mitochondria activities. Acamprosate at doses of 30 and 100 mg/kg, but not 10 mg/kg, exhibited significant neuroprotective effects against focal cerebral ischemic injury by markedly attenuating MCAO-induced neurological deficit, and reducing the infarct area. Meanwhile, acamprosate significantly improved mitochondrial energy metabolism, and countered the reduction of SOD and GSH-Px activities and elevation of MDA level induced by cerebral ischemia. Acamprosate might provide neuroprotection against the cerebral ischemia-induced injury through antioxidative actions in the brain.