Neuroprotective effects of SNX-185 in an in Vitro model of TBI with a second insult

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Purpose: 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.

Original languageEnglish (US)
Pages (from-to)141-153
Number of pages13
JournalRestorative Neurology and Neuroscience
Volume31
Issue number2
DOIs
StatePublished - 2013

Keywords

  • hypoxia
  • In Vitro
  • ischemia
  • neuronal cell death
  • rat
  • traumatic brain injury

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

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