Long-lasting alterations in neuronal calcium homeostasis in an in vitro model of stroke-induced epilepsy.
Altered calcium homeostatic mechanisms have been implicated in the development of acquired epilepsy in numerous models. Stroke is one of the leading brain injuries that cause acquired epilepsy, yet little is known concerning the molecular mechanisms underlying stroke-induced epileptogenesis. Recently an in vitro model of stroke-induced epilepsy was developed and characterized as a powerful tool to study the pathophysiology of injury and stroke-induced epileptogenesis. Using this glutamate injury-induced epileptogenesis model, we have investigated the role of altered calcium homeostatic mechanisms in the development and maintenance of stroke-induced epilepsy. Epileptic neurons manifested elevated intracellular calcium levels compared to control neurons independent of neuronal activity and seizure discharge for the remainder of the life of the neurons in culture. In addition, epileptic neurons were found to have alterations in the ability to reduce intracellular calcium levels following a calcium load. These long-term epileptic changes in calcium homeostasis were dependent on calcium during the initial glutamate injury. The data demonstrate that significant alterations in calcium homeostatic mechanisms occur in association with stroke-induced epilepsy and suggest that these changes may play a role in both the induction and maintenance of the epileptic phenotype in this model.
Sun
David A
DA
Department of Neurological Surgery, Vanderbilt University, Nashville, TN, USA.
Sombati
Sompong
S
Blair
Robert E
RE
DeLorenzo
Robert J
RJ
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D004827:Epilepsy / Q000503:physiopathology*; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000503:physiopathology*; D013995:Time
D018698:Glutamic Acid; D002118:Calcium