Epilepsia
The causative genes for lissencephaly—including LIS1, DCX, and TUBA1A—highlight the importance of a microtubule‐based transport pathway in cortical development and potentially in pathogenesis of focal cortical dysplasias. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado‐Escueta AV, eds) published...
The developmental origins of cortical and hippocampal interneurons in the rodent are discussed, in addition to a description of the transcriptional mechanisms that control their specification and differentiation. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado‐Escueta AV, eds) published by...
Neurotransmitters released from active synapses stimulate receptors on glia, which produce a neuromodulatory response by gliotransmitter release. When a local inflammatory reaction is induced in the brain by epileptogenic events, microglia and astrocytes are activated and release proinflammatory mediators, consequently the neuron–glia signaling may be perturbed, thereby provoking increased neuronal...
The thalamocortical system consists of widespread excitatory connections between cortical and subcortical structures. Synaptic excitation and inhibition play subcircuit‐specific roles in its function. Generalized absence seizures result from either increased/decreased inhibition or excitation, depending on the subcircuit, yet a common feature of absence seizures in thalamus is net increased inhibition,...
Very fast oscillations (VFOs; >70–80 Hz) precede and superimpose upon electrographic seizures. Knowing the cellular mechanisms of VFOs may offer clues to therapy. In vitro models, and ultrastructural and network modeling data, suggest that VFOs are generated by electrical coupling between principal neurons, and that VFOs are favored by the suppression of chemical neurotransmission. For an expanded...
Pathologic high‐frequency oscillations, believed to reflect basic neuronal disturbances responsible for epilepsy, are promising biologic markers that may be used in clinical studies to optimize surgical treatment of medically refractory epilepsy, and studies that seek to develop new therapies for treatment, and possible prevention, of epilepsy. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition...
Voltage‐gated calcium channels contribute to the control of excitability at both the cellular and neural network levels. Alterations in the expression or biophysical properties of specific subtypes of calcium channels can have pathophysiologic effects on the frequency and patterns of action potential firing and causally contribute to epileptic seizures. For an expanded treatment of this topic see...
γ‐Aminobutyric acid (GABA) mediates both fast synaptic inhibition and a tonic form of signaling that depends on high‐affinity, extrasynaptic GABAA receptors. Tonic inhibition may contribute to the generation of spike‐wave discharges. Because they have a profound effect on circuit excitability, tonically active GABAA receptors represent an important therapeutic target. For an expanded treatment of...
Enhanced glutamate synaptic transmission may be expected to alter the balance of excitation and inhibition in brain, leading to seizures. Several differences between epileptic and nonepileptic brains in presynaptic and postsynaptic glutamate mechanisms have been reported. These findings suggest that altered glutamate mechanisms contribute to the hyperexcitability of epileptic brain. For an expanded...
Chronic intermittent ethanol (CIE) treatment and withdrawal in rats produces behavioral changes that models human alcohol dependence, including increased seizure susceptibility, and can be explained by plastic changes in inhibitory neurotransmission involving γ‐aminobutyric acid (GABA)A receptors. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition...
Brain derived neurotrophic factor (BDNF) regulates diverse neuronal functions and plasticity, and its expression is increased by seizures. Here we review the evidence that actions of BDNF at TrkB receptors contribute to temporal lobe epilepsy. In addition, regulation of BDNF by steroid hormones might explain syndromes such as catamenial epilepsy. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition...
Epilepsy often results from a brain insult. Herein, I describe the complex time‐dependent alterations in glutamatergic and γ‐aminobutyric acid (GABA)ergic circuitry triggered by the initial insult. I will relate these modifications to the occurrence of the first spontaneous seizure, the development of epileptogenic networks, and associated cognitive deficits. For an expanded treatment of this topic...
Alterations in the distribution of GABAA receptors are likely to play pivotal roles in epilepsy. Current findings indicate that such changes are more complex than general increases or decreases in specific subunits and can involve differential changes in principal cells and interneurons, altered localization at synapses, and altered subunit partnerships. For an expanded treatment of this topic see...
Seizure‐induced hilar basal dendrites on dentate granule cells are observed in several rodent models of temporal lobe epilepsy. Ultrastructural evidence showed that basal dendrites receive predominantly excitatory synapses, including many from mossy fibers. Such highly interconnected granule cells with basal dendrites are suggested to enhance hyperexcitability within the dentate network. For an expanded...
Persistent neural stem cells generate dentate granule cells (DGCs) throughout life. Evidence suggests that aberrant neurogenesis contributes to epileptic structural abnormalities, but that normally integrating adult‐born DGCs may restore inhibition. Current research focuses on how epileptogenic insults alter neurogenesis, and whether restoring normal neurogenesis will attenuate epilepsy or its comorbidities...
Major comorbidities of epilepsy include cognitive impairment and behavioral dysfunction. The type and degree of these comorbidities is dependent upon etiology, age, electroencephalography (EEG) abnormalities, and seizure type and frequency. The hippocampus and prefrontal cortex appear particularly vulnerable to seizure‐induced dysfunction. Rodent studies allow investigators to understand the cellular...
Febrile seizures (FS) are common and are associated with increased probability of temporal lobe epilepsy (TLE). However, whether FS can provoke TLE in the nonpredisposed brain is unknown. Using an immature rat model, we established that long FS cause TLE, and that duration of FS governed the severity of epilepsy. Epileptogenesis was accompanied, perhaps causally, by ion channel dysfunction and inflammatory...
Posttraumatic epilepsy (PTE) is defined as a recurrent seizure disorder due to injury to the brain following head trauma. Traumatic brain injury (TBI) accounts for 20% of symptomatic epilepsy in the general population and 5% of all epilepsy. Prevention or suppression of the development of PTE is a major unmet challenge in medicine. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition...
The time course of development of spontaneous recurrent seizures is a sigmoid function of time after status epilepticus or perinatal stroke, which reflects underlying mechanisms of epileptogenesis. The increase in recurrent excitation after axon sprouting, along with death of specific γγ‐aminobutyric acid (GABA)ergic interneurons, may contribute to this temporal pattern of epileptogenesis. For an...
Neonatal hypoxic/ischemic encephalopathy is the most common cause of neonatal seizures, and these seizures are refractory to conventional antiseizure drugs and can lead to later life epilepsy and congitive deficits. Data from human tissue studies as well as rodent models suggest unique age‐specific mechanisms underlying these neonatal seizure and their consequences, and are leading to a number of...