title: Neuroprotective effects of 619C89, a use-dependent sodium channel blocker, in rat traumatic brain injury.
abstract: Release of the excitatory amino acid (EAA) neurotransmitter glutamate has been implicated in secondary tissue damage following central nervous system (CNS) trauma and ischemia. The present study evaluated the neuroprotective actions of 619C89, a sodium channel blocker that inhibits ischemia-induced glutamate release, on traumatic brain injury (TBI) in rats using a lateral fluid percussion model. Various motor-related behavioral outcomes were used to evaluate neurologic function. Glial fibrillary acidic protein (GFAP) immunostaining and Cresyl violet staining were used to assess the histological changes. Treatment with 619C89, at a dose of 30 mg/kg administered intravenously 15 min before brain injury, significantly attenuated behavioral deficits at 24 h and 1 week. At 2 weeks, neuronal loss in the CA1 and CA3 pyramidal cell layers of the hippocampus was significantly decreased by 619C89 administration. Treatment with this compound also significantly attenuated increases in GFAP-immunoreactivity in both ipsilateral and contralateral CA1 regions. The present results suggest a potential therapeutic role for sodium channel blockade and/or glutamate release inhibition in the treatment of TBI.
authors.affiliation: Department of Neurology, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: F Y
authors.initials: FY
authors.lastname: Sun
authors.forename: A I
authors.initials: AI
authors.lastname: Faden
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers; D013997:Time Factors
chemical_list: D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D026941:Sodium Channel Blockers; C081980:sipatrigine