Activation of astrocytes during epileptogenesis in the absence of neuronal degeneration.

The issue of whether neuronal degeneration is a primary factor in activation of astrocytes during epileptogenesis was addressed using the kindling model of epilepsy. No degenerative changes specific to the kindling process were observed in brain sections from kindled animals, sampled from the olfactory bulbs through to cerebellum and processed with the degeneration-sensitive cupric silver stain. Also, examination of lectin-stained sections did not reveal any reactive microglia. At the same time, reactive astrocytes, as judged by an increase in glial fibrillary acidic protein immunoreactivity and a de novo vimentin immunoreactivity, were prominent in amygdala, piriform cortex, entorhinal cortex and hippocampus. These results suggest that loss of neurones is not a prerequisite for establishment of epilepsy-prone state, that seizures of short duration do not necessarily result in neuronal death, and that in kindling, astrocytes are activated by factors that are not related to neuronal degeneration, but which are likely associated with abnormal neuronal activity.

Transfer kindling between sites in the entorhinal cortex-perforant path-dentate gyrus system.

Repeated electrical stimulation of forebrain sites can lead to an enhanced epileptogenic response (the kindling phenomenon). When stimulation is subsequently applied to related sites, these developments occur more rapidly (the transfer effect). Axonal pathways do not support epileptiform discharge, so it is generally assumed that the kindling develops, when these pathways are stimulated, in the target structures of those pathways. Consequently, transfer kindling should be immediate, or at least very rapid. Primary and 'transfer' kindling effects were examined in the excitatory, monosynaptically coupled, entorhinal cortex-dentate gyrus system. Transfer kindling was begun following either a 24 h delay or a 4 week delay between the last primary site convulsion and the start of transfer kindling in the secondary site. A 4 week delay between kindling sites was chosen to minimize the effects of a previously reported transient suppression of transfer kindling and the increased inhibition that has been shown to develop in the dentate gyrus as a result of kindling the perforant path. Although there was a significant transfer to the dentate gyrus following perforant path stimulation, the dentate gyrus still required a mean of 18.5 (24 h delay) and 20.3 (4 week delay) stimulations to reach criterion. In the entorhinal cortex, there was a significant positive transfer following primary kindling of the perforant path only in the group in which transfer kindling was begun after a 4 week delay. When the perforant path itself was the transfer site, there was a significant savings in number of afterdischarges needed to reach criterion following dentate gyrus kindling but no savings following entorhinal cortex kindling.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of kindling beyond the 'stage 5' criterion on paired-pulse depression and hilar cell counts in the dentate gyrus.

Recent experiments have indicated that recurrent inhibition in the dentate gyrus, as measured with paired-pulse tests, is reduced following the induction of status epilepticus. Also, a loss of cells in the hilus has been reported, and it has been suggested that the two effect might be related. In this experiment, we have monitored paired-pulse depression and counted cells in the hilus in animals that have been kindled well beyond the typical stage 5 criterion. Responses evoked in the dentate gyrus by paired-pulse stimulation of the perforant path were monitored before and after kindling of the perforant path. One group of animals served as controls and received no kindling stimulations. Another group was kindled to 4 stage 5 seizures and then allowed to recover for 2 months. A third group was kindled to 44 stage 5 seizures and then allowed to recover for at least 5 weeks. Paired-pulse tests were taken at 1 week intervals during the kindling and recovery phases. Paired-pulse inhibition increased during kindling, peaked after 4 stage 5 seizures, remained enhanced throughout the additional 40 stage 5 seizures, and recovered towards baseline over a period of about 5 weeks. Upon completion of this phase of the experiment, cell counts were taken in the hilar regions of the Nissl stained brain sections. There was a significant reduction in number of cells in the tissue from kindled animals, compared to controls, but there was no significant difference between the 2 kindled groups.(ABSTRACT TRUNCATED AT 250 WORDS)