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.