title: Neuroprotective effects of SNX-185 in an in vitro model of TBI with a second insult.
abstract: OBJECTIVE
  Second insults following traumatic brain injury (TBI), such as ischemia and hypoxia, significantly worsen outcome in patients and in experimental models of TBI. Following TBI there is a pathological increase in intracellular calcium, triggering cellular mechanisms of dysfunction and death. N-type specific voltage gated calcium channel (VGCC) blockers reduce cell death in both in vitro mechanical strain injury (MSI) and in vivo models of TBI, but they have not been previously explored in a model of TBI followed by a second insult.
  
  
  METHODS
  In the following studies, cortical neurons and astrocytes experienced MSI followed by incubation in 20% CO2. Cultures were treated with the N-type VGCC blocker, ω-conopeptide SNX-185 (1 μM), 5-minutes post-injury and intracellular calcium accumulation was assessed at 3, 6 and 24 h. Neuronal viability was assessed 24 h after MSI.
  
  
  RESULTS
  Increasing incubator CO2 to 20% significantly increased calcium accumulation and cell death regardless of MSI severity. Treatment with 1 μM of SNX-185 significantly reduced the accumulation of calcium 3 hours following injury and increased the number of viable neurons 24 h post-injury and incubation in 20% CO2.
  
  
  CONCLUSIONS
  In vitro models provide a critical tool for identifying roles of cell specific mechanisms involved in neuronal dysfunction and death following injury. These data demonstrate the potential of N-type VGCC blockers in reducing the damaging effects of TBI and second insults.
authors.affiliation: Department of Neurological Surgery, University of California, Davis, CA 95817, USA. kiarash.shahlaie@ucdmc.ucdavis.edu
authors.forename: Kiarash
authors.initials: K
authors.lastname: Shahlaie
authors.forename: Gene G
authors.initials: GG
authors.lastname: Gurkoff
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Lyeth
authors.forename: J Paul
authors.initials: JP
authors.lastname: Muizelaar
authors.forename: Robert F
authors.initials: RF
authors.lastname: Berman
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000293:injuries*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D012008:Recurrence; D020960:omega-Conotoxins / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D020960:omega-Conotoxins; C087968:omega-conotoxin TVIA; D002118:Calcium