Chronic neocortical epileptogenesis in vitro.
1. We used an in vitro model to explore critical aspects of chronic epileptogenesis. Partial neocortical isolations having intact blood supply were made in rat and guinea pig from postnatal day 7 to 34 and then examined 1 to 150 days later in standard brain slice preparations. 2. The epileptogenic potential of several different types of lesions was assessed. Slices containing transcortical (i.e., gray matter) lesions, with or without a contiguous white matter injury (i.e., "undercut"), developed chronic epileptogenesis after a latency of approximately 1-2 wk, manifested by evoked and spontaneous "interictal" discharges and evoked "ictal" events. The region of hyperexcitability did not extend beyond approximately 2 mm from the chronic transcortical lesion and was rarely observed in slices having only an apparent white matter injury. 3. Multiple recordings and current source density (CSD) analysis identified layer V as the source of the interictal discharge. 4. Significant differences in CSD profiles of the evoked interictal discharge occurred between chronically epileptogenic slices and control (noninjured) slices bathed in the convulsant, bicuculline methiodide, suggesting that mechanisms other than disinhibition must be involved in posttraumatic epileptogenesis. 5. Interictal events were blocked in most but not all chronically injured slices by application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovalerate (D-AP5), suggesting that non-NMDA receptors were predominantly involved in some preparations. 6. This model of chronic epileptogenesis in vitro will be useful in studies relevant to mechanisms of posttraumatic epilepsy in man.
Hoffman
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SN
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, California 94305-5300.
Salin
P A
PA
Prince
D A
DA
D000818:Animals; D001931:Brain Mapping; D016922:Cellular Senescence / Q000502:physiology*; D002540:Cerebral Cortex / Q000293:injuries / Q000503:physiopathology*; D046508:Culture Techniques; D004827:Epilepsy / Q000503:physiopathology*; D004834:Epilepsy, Post-Traumatic / Q000503:physiopathology; D005071:Evoked Potentials / Q000502:physiology; D006168:Guinea Pigs; D009044:Motor Cortex / Q000293:injuries / Q000503:physiopathology; D009415:Nerve Net / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013003:Somatosensory Cortex / Q000293:injuries / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate