Epileptogenesis

About: Epileptogenesis is a research topic. Over the lifetime, 4218 publications have been published within this topic receiving 170809 citations.

What is the biological significance of BDNF mRNA targeting in the dendrites? Clues from epilepsy and cortical development.

Abstract: The neurotrophin brain-derived neurotrophic factor (BDNF) is a regulatory factor of several, partially contrasting, aspects of the biology of neural cells, including survival, growth, differentiation, and cell death. Regulation of the local availability of BDNF at distinct subcellular domains such as the cell soma, dendrites, axons, and spines appears to be the key to conferring spatial and temporal specificity of the different effects elicited by this neurotrophin. This article reviews recent findings in the context of epileptogenesis and visual cortex maturation that showed that different BDNF messenger RNA (mRNA) transcripts are localized at different subcellular locations in hippocampal and cortical neurons. It also reviews findings demonstrating that strong depolarizing stimuli, both in vitro and in vivo, elicit accumulation of BDNF mRNA and protein in the distal dendrites through a signaling pathway involving the activation of the N-methyl-D-aspartate and tyrosine kinase B receptors and an intracellular increase in Ca2+ concentration. Finally, this article proposes that the regulation of the delivery of BDNF mRNA and protein to the different subcellular domains--particularly the dendritic compartment--may represent a fundamental aspect of the processes of cellular and synaptic morphological rearrangements underlying epileptogenesis and postnatal development of the visual cortex.

Long-latency auditory event-related potentials in epilepsy.

Abstract: Long latency auditory event-related potentials have been shown to change in patients with cerebral dysfunction. Some seizure patients with no evidence of brain damage or mental retardation show altered interictal cognitive and memory function. Long-latency auditory event-related potentials to tone stimulation were recorded in nineteen control subjects and seventeen patients with complex partial or partial and secondarily generalized seizures who had no evidence of brain damage, retardation, or drug intoxication, and whose seizures were controlled when studied. The latencies of N2 and P3 components were significantly longer in seizure patients than control subjects, and the P3 waveform was significantly greater in amplitude in epileptics. These findings suggest that cognitive event-related potentials are affected by partial epilepsy. The changes may be related to the recently reported involvement of the hippocampus in ERP generation, or to loss or alteration of modulatory functions, possibly cholinergic in nature, in the temporal lobe consequent upon epileptogenesis.

Inhibition of calcium/calmodulin kinase II alpha subunit expression results in epileptiform activity in cultured hippocampal neurons.

Abstract: Several models that develop epileptiform discharges and epilepsy have been associated with a decrease in the activity of calmodulin-dependent kinase II. However, none of these studies has demonstrated a causal relationship between a decrease in calcium/calmodulin kinase II activity and the development of seizure activity. The present study was conducted to determine the effect of directly reducing calcium/calmodulin-dependent kinase activity on the development of epileptiform discharges in hippocampal neurons in culture. Complimentary oligonucleotides specific for the α subunit of the calcium/calmodulin kinase were used to decrease the expression of the enzyme. Reduction in kinase expression was confirmed by Western analysis, immunocytochemistry, and exogenous substrate phosphorylation. Increased neuronal excitability and frank epileptiform discharges were observed after a significant reduction in calmodulin kinase II expression. The epileptiform activity was a synchronous event and was not caused by random neuronal firing. Furthermore, the magnitude of decreased kinase expression correlated with the increased neuronal excitability. The data suggest that decreased calmodulin kinase II activity may play a role in epileptogenesis and the long-term plasticity changes associated with the development of pathological seizure activity and epilepsy.