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Traumatic brain injury causes a long‐lasting calcium (Ca 2+ )‐plateau of elevated intracellular Ca levels and altered Ca 2+ homeostatic mechanisms in hippocampal neurons surviving brain injury
Author(s) -
Sun David A.,
Deshpande Laxmikant S.,
Sombati Sompong,
Baranova Anya,
Wilson Margaret S.,
Hamm Robert J.,
DeLorenzo Robert J.
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06156.x
Subject(s) - traumatic brain injury , homeostasis , pathophysiology , calcium metabolism , hippocampal formation , medicine , status epilepticus , homeostatic plasticity , neuroscience , calcium , endocrinology , biology , synaptic plasticity , epilepsy , psychiatry , receptor , metaplasticity
Traumatic brain injury (TBI) survivors often suffer chronically from significant morbidity associated with cognitive deficits, behavioral difficulties and a post‐traumatic syndrome and thus it is important to understand the pathophysiology of these long‐term plasticity changes after TBI. Calcium (Ca 2+ ) has been implicated in the pathophysiology of TBI‐induced neuronal death and other forms of brain injury including stroke and status epilepticus. However, the potential role of long‐term changes in neuronal Ca 2+ dynamics after TBI has not been evaluated. In the present study, we measured basal free intracellular Ca 2+ concentration ([Ca 2+ ] i ) in acutely isolated CA3 hippocampal neurons from Sprague–Dawley rats at 1, 7 and 30 days after moderate central fluid percussion injury. Basal [Ca 2+ ] i was significantly elevated when measured 1 and 7 days post‐TBI without evidence of neuronal death. Basal [Ca 2+ ] i returned to normal when measured 30 days post‐TBI. In contrast, abnormalities in Ca 2+ homeostasis were found for as long as 30 days after TBI. Studies evaluating the mechanisms underlying the altered Ca 2+ homeostasis in TBI neurons indicated that necrotic or apoptotic cell death and abnormalities in Ca 2+ influx and efflux mechanisms could not account for these changes and suggested that long‐term changes in Ca 2+ buffering or Ca 2+ sequestration/release mechanisms underlie these changes in Ca 2+ homeostasis after TBI. Further elucidation of the mechanisms of altered Ca 2+ homeostasis in traumatized, surviving neurons in TBI may offer novel therapeutic interventions that may contribute to the treatment and relief of some of the morbidity associated with TBI.