[The microglial activation and the expression of heat shock protein 27 through the propagation pathway of kainic acid-induced hippocampal seizure in the rat].

We studied activation of microglia and expression of the 27 kDa heat shock protein (HSP27) in the brain during kainic acid-induced acute hippocampal seizures in rats. The microglial activation was observed at 6 hrs after seizure induction, but the expression of HSP27 was delayed until 3 days after seizure induction. The gross anatomical distributions of the two phenomena in the brain structures were almost identical, being localized not only in the primary focus at the dorsal hippocampus ipsilateral to the kainic acid injection, but also in selected remote brain structures that was highly consistent with the propagation pathways of the hippocampal seizure as detected previously by metabolic mapping. These structures included the hippocampus, amygdala, entorhinal cortex, piriform cortex, sensorimotor cortex, hypothalamus and thalamus. A close observation, however, revealed a difference in distribution of the two phenomena in the layers of the contralateral hippocampus: The HSP27 expression showed a layer-specific distribution, being localized selectively in the molecular layer and hilus of the dentate gyrus, and the radiatum and molecular layers of the CA-3 subfield suggesting the expression in the neuropil. On the other hand, the distribution of the microglial activation was non-specific to the layers, being scattered in the whole regions of the dorsal hippocampus. There were no apparent morphological changes in the neurons in these structures except for the ipsilateral dorsal hippocampus, by light microscopic examinations with hematoxylin-eosin staining. These findings thus indicate that activation of microglial cells and expression of HSP27 occur transsynaptically by epileptic activities through the propagation pathways of hippocampal seizure and suggest that these phenomena may reflect a part of early microenvironmental alterations in epileptic brain.

[A case of MELAS presenting complex partial status epilepticus].

We reported a 37-year-old man who presented complex partial status epilepticus as the initial symptom of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). He showed fluctuating consciousness disturbance, left homonymous hemianopsia, and paroxysmal conjugated eye deviation to the left. The lactic acid level was elevated in blood and CSF, and ragged-red fibers were observed in the biopsied muscle. MRI demonstrated T2-prolonged lesions in the right occipito-parieto-temporal lobes. Since a mutation of mitochondrial DNA (A3243G) was identified, he was diagnosed as having MELAS. On an ictal record, high amplitude, rhythmic sharp waves were observed at right parieto-temporo-occipital region. High amplitude slow waves were also observed on the right hemisphere, especially in the right frontal lobe. These ictal discharges gradually decreased at their amplitude and in frequency, and then ictal EEG turned to the interictal EEG. During an ictal period, conjugated eye deviation to the left side and consciousness loss were observed. These seizures were observed once every several minutes. During the interictal period, sharp waves and sharp-wave complexes were observed frequently at right parietal and posterior temporal lobes. The venous injection of diazepam (10 mg) normalized EEG quickly. When consciousness loss, especially fluctuating, was observed in the patients of MELAS, complex partial status epilepticus should be considered.

Microglial activation by epileptic activities through the propagation pathway of kainic acid-induced hippocampal seizures in the rat.

We studied the distribution of activated microglia in the brain during kainic acid-induced acute hippocampal seizures in rats. Although no microglial activation was observed 4 h after seizure induction, activation was detected in the primary focus and also in other selected structures in the limbic and non-limbic structures after 8 and 24 h, in the absence of any obvious morphological changes in the neurons. The structures with activated microglia were highly consistent with those included in the propagation pathways of the hippocampal seizures. These findings thus suggest that the microglial cells are activated through the propagation pathways by the seizure activities that propagate transynaptically from the primary focus, even without any apparent neuronal injury.