title: Evidence that injury-induced changes in hippocampal neuronal calcium dynamics during epileptogenesis cause acquired epilepsy.
abstract: Alterations in hippocampal neuronal Ca(2+) and Ca(2+)-dependent systems have been implicated in mediating some of the long-term neuroplasticity changes associated with acquired epilepsy (AE). However, there are no studies in an animal model of AE that directly evaluate alterations in intracellular calcium concentration ([Ca(2+)](i)) and Ca(2+) homeostatic mechanisms (Ca(2+) dynamics) during the development of AE. In this study, Ca(2+) dynamics were evaluated in acutely isolated rat CA1 hippocampal, frontal, and occipital neurons in the pilocarpine model by using [Ca(2+)](i) imaging fluorescence microscopy during the injury (acute), epileptogenesis (latency), and chronic-epilepsy phases of the development of AE. Immediately after status epilepticus (SE), hippocampal neurons, but not frontal and occipital neurons, had significantly elevated [Ca(2+)](i) compared with saline-injected control animals. Hippocampal neuronal [Ca(2+)](i) remained markedly elevated during epileptogenesis and was still elevated indefinitely in the chronic-epilepsy phase but was not elevated in SE animals that did not develop AE. Inhibiting the increase in [Ca(2+)](i) during SE with the NMDA channel inhibitor MK801 was associated in all three phases of AE with inhibition of the changes in Ca(2+) dynamics and the development of AE. Ca(2+) homeostatic mechanisms in hippocampal neurons also were altered in the brain-injury, epileptogenesis, and chronic-epilepsy phases of AE. These results provide evidence that [Ca(2+)](i) and Ca(2+)-homeostatic mechanisms are significantly altered during the development of AE and suggest that altered Ca(2+) dynamics may play a role in the induction and maintenance of AE and underlie some of the neuroplasticity changes associated with the epileptic phenotype.
authors.affiliation: Departments of Neurology, Pharmacology and Toxicology, and Biochemistry and Molecular Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0599, USA.
authors.forename: Mohsin
authors.initials: M
authors.lastname: Raza
authors.forename: Robert E
authors.initials: RE
authors.lastname: Blair
authors.forename: Sompong
authors.initials: S
authors.lastname: Sombati
authors.forename: Dawn S
authors.initials: DS
authors.lastname: Carter
authors.forename: Laxmikant S
authors.initials: LS
authors.lastname: Deshpande
authors.forename: Robert J
authors.initials: RJ
authors.lastname: DeLorenzo
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004827:Epilepsy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D006706:Homeostasis; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D016291:Dizocilpine Maleate; D002118:Calcium