Astrocyte processes surround synapses and are involved in uptake and release of ions and neurotransmitters. These cells also possess functional, specific glutamate receptor subtypes. Astrocytes influence neuronal excitability and synaptic transmission involving them in seizure initiation, propagation or termination (Neary et al, 1988). Astrocyte syncitiums are capable of sustaining glutamate-induced Ca2+ oscillations and Ca2+ waves. The ACPD receptor stimulates the production of IP3 and the release of intracellularly stored Ca2+. AMPA and kainate appear to induce a membrane influx of Ca2+. Epileptogenic foci might accumulate high glutamate levels from abnormal neuronal firing or abnormal glutamate uptake into astrocytes. Resulting astrocytic Ca2+ waves could increase the excitability of neighboring synapses. Hypothetically then, a localized area of excitability could spread to brain regions which are not synaptically connected. Tissues removed from two human models of epilepsy (sclerotic hippocampus and tumor related cortex) will be cultured. We are proposing to investigate cells from similar brain regions differing only in their epileptic experience. Astrocytes are cultured from regions of the cortex and hippocampus which are predominantly innervated by glutaminergic pathways. Preliminary evidence from time-lapse confocal scanning laser microscopy has shown that astrocytes cultured from hyperexcitable regions of cortex show inherent hyperexcitability in Ca2+ i oscillations following exposure to glutamate. In contrast astrocytes cultured from tumor loci show an initial Ca2+ spike in response to glutamate but exhibit no subsequent oscillations. Astrocytic response from both these tissues are dramatically different from regions with normal EEG activity. In addition, astrocytes from the parahippocampal cortex exhibit a hyperexcitability in Ca2+ i oscillations. Changes in astrocytic neurochemistry and physiology may reflect the primary etiology of the epileptic focus or some secondary adaptive changes caused by the drastically altered cellular environment that develops during the seizure.
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