title: Do sodium channel blockers have neuroprotective effect after onset of ischemic insult?
abstract: OBJECTIVE
  Cerebral ischemia causes a series of pathophysiologic events that may result in cerebral infarct. Some neurons are more vulnerable to ischemia, particularly pyramidal neurons in the hippocampal CA1 region. Pharmacologic intervention for treatment of cerebral ischemia aims to counteract secondary neurotoxic events or to interrupt the progression of this process. In the present study, we compare the neuroprotective effects of sodium channel blockers (mexiletine, riluzole and phenytoin) and investigate whether they have neuroprotective effect when given after ischemic insult.
  
  
  METHODS
  A transient global cerebral ischemia model was performed in this study by clipping bilateral common carotid arteries during 45 minutes. Riluzole (8 mg/kg), mexiletine (80 mg/kg) and phenytoin (200 mg/kg) were injected into the rats intraperitoneally 30 minutes before or after reperfusion. Lipid peroxidation levels and cerebral water contents were evaluated 24 hours after ischemia. Histopathologic assessment of hippocampal region was determined 7 days after ischemia.
  
  
  RESULTS
  Riluzole, mexiletine and phenytoin treatment after global ischemia significantly decreased water content of the ischemic brain (p<0.05 for each). No significant difference was observed in cerebral edema among the drug treatment groups (p>0.05). When pre-treatment and post-treatment groups were compared with each other, only riluzole pre-treatment group revealed better result for cerebral edema (p<0.05). Pre-treatment with these drugs revealed significantly better results for the malonyldialdehyde (MDA) level and the number of survival neuron on the hippocampal region than the post-treatment groups.
  
  
  CONCLUSIONS
  It is demonstrated that riluzole, mexiletine and phenytoin are potent neuroprotective agents in the rat model of transient global cerebral ischemia, but they are more effective when given before onset of the ischemia.
authors.affiliation: Department of Neurosurgery, School of Medicine, Inonu University, Malatya, Turkey. atesozkan@hotmail.com
authors.forename: Ozkan
authors.initials: O
authors.lastname: Ates
authors.forename: Suleyman R
authors.initials: SR
authors.lastname: Cayli
authors.forename: Iclal
authors.initials: I
authors.lastname: Gurses
authors.forename: Aysun Bay
authors.initials: AB
authors.lastname: Karabulut
authors.forename: Neslihan
authors.initials: N
authors.lastname: Yucel
authors.forename: Ayhan
authors.initials: A
authors.lastname: Kocak
authors.forename: Celal Ozbek
authors.initials: CO
authors.lastname: Cakir
authors.forename: Saim
authors.initials: S
authors.lastname: Yologlu
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion / Q000379:methods; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D018709:Statistics, Nonparametric
chemical_list: D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers