title: Alterations in neuronal calcium levels are associated with cognitive deficits after traumatic brain injury.
abstract: Traumatic brain injury (TBI) survivors often suffer from a post-traumatic syndrome with deficits in learning and memory. Calcium (Ca(2+)) has been implicated in the pathophysiology of TBI-induced neuronal death. However, the role of long-term changes in neuronal Ca(2+) 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 Ca(2+) ([Ca(2+)](i)) in acutely isolated rat CA3 hippocampal neurons using the Ca(2+) 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 [Ca(2+)](i) and cognitive deficits. Moderate TBI did not cause significant hippocampal neuronal death. However, basal [Ca(2+)](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 [Ca(2+)](i) and cognitive functions had returned to normal. Pretreatment with MK-801 blocked this elevation in [Ca(2+)](i) and also prevented MWM deficits. These studies provide evidence for a link between elevated [Ca(2+)](i) and altered cognition. Since no significant neuronal death was observed, the alterations in Ca(2+) 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.
authors.affiliation: Department of Neurology, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Laxmikant S
authors.initials: LS
authors.lastname: Deshpande
authors.forename: David A
authors.initials: DA
authors.lastname: Sun
authors.forename: Sompong
authors.initials: S
authors.lastname: Sombati
authors.forename: Anya
authors.initials: A
authors.lastname: Baranova
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Wilson
authors.forename: Elisa
authors.initials: E
authors.lastname: Attkisson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hamm
authors.forename: Robert J
authors.initials: RJ
authors.lastname: DeLorenzo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000150:complications*; D002118:Calcium / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology*; D018782:Maze Learning / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
chemical_list: D002118:Calcium