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Abstract: Traumatic brain injury (TBI) survivors often suffer from a post-traumatic syndrome with deficits in learning and memory. Calcium (Ca2+) has been implicated in the pathophysiology of TBI-induced neuronal death. However, the role of long-term changes in neuronal Ca2+ function in surviving neurons and the potential impact on TBI-induced cognitive impairments are less understood. Here we evaluated neuronal death and basal free intracellular Ca2+ ([Ca2+]i) in acutely isolated rat CA3 hippocampal neurons using the Ca2+ indicator, Fura-2, at seven and thirty days after moderate central fluid percussion injury. In moderate TBI, cognitive deficits as evaluated by the Morris Water Maze (MWM), occur after injury but resolve after several weeks. Using MWM paradigm we compared alterations in [Ca2+]i and cognitive deficits. Moderate TBI did not cause significant hippocampal neuronal death. However, basal [Ca2+]i was significantly elevated when measured seven days post-TBI. At the same time, these animals exhibited significant cognitive impairment (F 2,25 =3.43, p <0.05). When measured 30 days post-TBI, both basal [Ca2+]i and cognitive functions had returned to normal. Pretreatment with MK-801 blocked this elevation in [Ca2+]i and also prevented MWM deficits. These studies provide evidence for a link between elevated [Ca2+]i and altered cognition. Since no significant neuronal death was observed, the alterations in Ca2+ homeostasis in the traumatized, but surviving neurons may play a role in the pathophysiology of cognitive deficits that manifest in the acute setting after TBI and represent a novel target for therapeutic intervention following TBI. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Moderately head injured patients often suffer long term neurological sequelae. There is no therapy for brain trauma and current treatments aim only to minimize secondary damage. These secondary effects are often triggered by the inability to re-establish ionic homeostasis after injury, due to large energy demands. Recent reports have demonstrated that neurons are capable of utilizing lactate as an energy source, thus this report examines the usefulness of lactate administration in the attenuation of behavioural deficits following a moderate brain injury. Lactate infusion (i.v.) was started 30 min after lateral fluid percussion injury and continued for 3 h. Cognitive deficits were determined using the Morris water maze. Lactate infused injured animals demonstrated significantly less cognitive deficits than saline infused injured animals. Thus, lactate infusion attenuated the cognitive deficits normally observed in this model, and therefore may provide moderately head injured patients with a treatment to help ameliorate the sequelae. [Copyright &y& Elsevier]