Epileptogenesis

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

Early Deficits in Spatial Memory and Theta Rhythm in Experimental Temporal Lobe Epilepsy

Abstract: Patients with temporal lobe epilepsy (TLE), the most common form of epilepsy in adults, often display cognitive deficits. The time course and underlying mechanisms of cognitive decline remain unknown during epileptogenesis (the process leading to epilepsy). Using the rat pilocarpine model of TLE, we performed a longitudinal study to assess spatial and nonspatial cognitive performance during epileptogenesis. In parallel, we monitored interictal-like activity (ILA) in the hippocampal CA1 region, as well as theta oscillations, a brain rhythm central to numerous cognitive processes. Here, we report that spatial memory was altered soon after pilocarpine-induced status epilepticus, i.e., already during the seizure-free, latent period. Spatial deficits correlated with a decrease in the power of theta oscillations but not with the frequency of ILA. Spatial deficits persisted when animals had spontaneous seizures (chronic stage) without further modification. In contrast, nonspatial memory performances remained unaffected throughout. We conclude that the reorganization of hippocampal circuitry that immediately follows the initial insult can affect theta oscillation mechanisms, in turn, resulting in deficits in hippocampus-dependent memory tasks. These deficits may be dissociated from the process that leads to epilepsy itself but could instead constitute, as ILA, early markers in at-risk patients and/or provide beneficial therapeutic targets.

Epileptogenesis in Experimental Models

Abstract: Epileptogenesis refers to a phenomenon in which the brain undergoes molecular and cellular alterations after a brain-damaging insult, which increase its excitability and eventually lead to the occurrence of recurrent spontaneous seizures. Common epileptogenic factors include traumatic brain injury (TBI), stroke, and cerebral infections. Only a subpopulation of patients with any of these brain insults, however, will develop epilepsy. Thus, there are two great challenges: (1) identifying patients at risk, and (2) preventing and/or modifying the epileptogenic process. Target identification for antiepileptogenic treatments is difficult in humans because patients undergoing epileptogenesis cannot currently be identified. Animal models of epileptogenesis are therefore necessary for scientific progress. Recent advances in the development of experimental models of epileptogenesis have provided tools to investigate the molecular and cellular alterations and their temporal appearance, as well as the epilepsy phenotype after various clinically relevant epileptogenic etiologies, including TBI and stroke. Studying these models will lead to answers to critical questions such as: Do the molecular mechanisms of epileptogenesis depend on the etiology? Is the spectrum of network alterations during epileptogenesis the same after various clinically relevant etiologies? Is the temporal progression of epileptogenesis similar? Work is ongoing, and answers to these questions will facilitate the identification of molecular targets for antiepileptogenic treatments, the design of treatment paradigms, and the determination of whether data from one etiology can be extrapolated to another.

Seizure-induced neurogenesis: are more new neurons good for an adult brain?

Abstract: The idea that neural stem cells may play a role in the pathophysiology or potential treatment of specific epilepsy syndromes is relatively new. This notion relates directly to advances in the field of stem cell biology over the past decade, which have confirmed prior theories that both neural stem cells and neurogenesis, the birth of new neurons, persist in specific regions of the adult mammalian brain. The physiological role of persistent neurogenesis is not known, although recent work implicates this process in specific learning and memory tasks. Knowledge of the normal neurogenic pathways in the mature brain has led to recent studies of neurogenesis in rodent models of acute seizures or epileptogenesis. Most of these studies have examined neurogenesis in the adult rodent dentate gyrus, and current evidence indicates that single brief or prolonged seizures, as well as repeated kindled seizures, increase dentate granule cell (DGC) neurogenesis. The models studied to date include pilocarpine and kainic acid models of temporal lobe epilepsy, limbic kindling, and intermittent perforant path stimulation. Recent work also suggests that pilocarpine-induced status epilepticus increases rostral forebrain subventricular zone (SVZ) neurogenesis and caudal SVZ gliogenesis. Several lines of evidence implicate newly generated neurons in structural and functional network abnormalities in the epileptic hippocampal formation of adult rodents. These abnormalities include aberrant mossy fiber reorganization, persistence of immature DGC structure (e.g. basal dendrites), and the abnormal migration of newborn neurons to ectopic sites in the dentate gyrus. Taken together, these findings suggest a pro-epileptogenic role of seizure- or injury-induced neurogenesis in the epileptic hippocampal formation. However, the induction of forebrain SVZ neurogenesis and directed migration to injury after seizures and other brain insults underscores the potential therapeutic use of neural stem cells as a source for neuronal replacement after injury.