Impaired K+ homeostasis and altered electrophysiological properties of post-traumatic hippocampal glia

Traumatic brain injury (TBI) can be associated with memory impairment, cogn itive deficits, or seizures, all of which can reflect altered hippocampal f unction. Whereas previous studies have focused on the involvement of neuron al loss in posttraumatic hippocampus, there has been relatively little unde rstanding of changes in ionic homeostasis, failure of which can result in n euronal hyperexcitability and abnormal synchronization. Because glia play a crucial role in the homeostasis of the brain microenvironment, we investig ated the effects of TBI on rat hippocampal glia. Using a fluid percussion i njury (FPI) model and patch-clamp recordings from hippocampal slices, we ha ve found impaired glial physiology 2 d after FPI. Electrophysiologically, w e observed reduction in transient outward and inward K+ currents. To assess the functional consequences of these glial changes, field potentials and e xtracellular K+ activity were recorded in area CA3 during antidromic stimul ation. An abnormal extracellular K+ accumulation was observed in the posttr aumatic hippocampal slices, accompanied by the appearance of CA3 afterdisch arges. After pharmacological blockade of excitatory synapses and of K+ inwa rd currents, uninjured slices showed the same altered K+ accumulation in th e absence of abnormal neuronal activity. We suggest that TBI causes loss of K+ conductance in hippocampal glia that results in the failure of glial K homeostasis, which in turn promotes abnormal neuronal function. These find ings provide a new potential mechanistic link between traumatic brain injur y and subsequent development of disorders such as memory loss, cognitive de cline, seizures, and epilepsy.