title: Traumatic brain injury causes a long-lasting calcium (Ca2+)-plateau of elevated intracellular Ca levels and altered Ca2+ homeostatic mechanisms in hippocampal neurons surviving brain injury.
abstract: 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 (Ca2+) 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 Ca2+ dynamics after TBI has not been evaluated. In the present study, we measured basal free intracellular Ca2+ concentration ([Ca2+](i)) in acutely isolated CA3 hippocampal neurons from Sprague-Dawley rats at 1, 7 and 30 days after moderate central fluid percussion injury. Basal [Ca2+](i) was significantly elevated when measured 1 and 7 days post-TBI without evidence of neuronal death. Basal [Ca2+](i) returned to normal when measured 30 days post-TBI. In contrast, abnormalities in Ca2+ homeostasis were found for as long as 30 days after TBI. Studies evaluating the mechanisms underlying the altered Ca2+ homeostasis in TBI neurons indicated that necrotic or apoptotic cell death and abnormalities in Ca2+ influx and efflux mechanisms could not account for these changes and suggested that long-term changes in Ca2+ buffering or Ca2+ sequestration/release mechanisms underlie these changes in Ca2+ homeostasis after TBI. Further elucidation of the mechanisms of altered Ca2+ 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.
authors: Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors: David A
authors: DA
authors: Sun
authors: Laxmikant S
authors: LS
authors: Deshpande
authors: Sompong
authors: S
authors: Sombati
authors: Anya
authors: A
authors: Baranova
authors: Margaret S
authors: MS
authors: Wilson
authors: Robert J
authors: RJ
authors: Hamm
authors: Robert J
authors: RJ
authors: DeLorenzo
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D007424:Intracellular Fluid / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013995:Time
chemical_list: D002118:Calcium