In vitro mechanical strain trauma alters neuronal calcium responses: Implications for posttraumatic epilepsy

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13 Scopus citations

Abstract

Traumatic brain injury (TBI) is known to initiate a series of chemical cascades resulting in neuronal dysfunction and death. Epidemiology studies have found that a prior incidence of TBI is the most important cause of remote symptomatic epilepsy in young adults and children. TBI-induced changes in neuronal sensitivity to stimulation may contribute to acute seizures and the eventual generation of epilepsy. This study examined TBI-induced changes in neuronal sensitivity to stimulation by measuring intracellular calcium ([Ca ++] i) responses in neurons during glutamate application in vitro. Initial experiments examined neuronal and glial cell death and determined that a 31% mechanical strain trauma to mixed neuronal-astrocyte rat cortical cultures produced a trend, but no significant cell death at 48 h after injury. Subsequent experiments utilized this magnitude of trauma to examine the sensitivity of cortical neurons to changes in [Ca ++] i in response to 100-μm glutamate at five time points postinjury (1, 6, 24, 48, and 72 h). Traumatically strain-injured neurons responded with a dynamic change in the accumulation of [Ca ++] i, with a significant increase at 48 h and a significant decrease at 72 h as compared to uninjured cultures. These data highlight that TBI leads to abnormal responsiveness to stimulation, an indicator of neuronal dysfunction in surviving cells. Such changes in sensitivity to stimulation may also be associated with changes in excitability in the first hours to days after TBI, and may play a role in early posttraumatic seizures observed in patients with TBI. In addition, this study provides an in vitro paradigm for testing the function of surviving cells following treatment interventions targeted at reducing cell death and dysfunction.

Original languageEnglish (US)
Pages (from-to)53-60
Number of pages8
JournalEpilepsia
Volume53
Issue numberSUPPL. 1
DOIs
StatePublished - Jun 2012

Keywords

  • Calcium
  • Cell culture
  • Excitability
  • Glutamate
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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