Role of glutamate and GABA in the pathophysiology of epilepsy

Abstract

Epilepsy, a paroxysmal disorder characterized by abnormal neuronal discharges, is common in children. While the causes of epilepsy are many, the fundamental disorder is secondary to abnormal synchronous discharges of a network of neurons. Whether or not a seizure occurs in a child depends upon the balance between excitability and inhibition. Central nervous system neurotransmitters have significant effects on neuronal excitability and play a pivotal role in brain excitability. The most common excitatory neurotransmitter in the brain, glutamate, has been implicated in both the initiation and propagation of seizures as well as brain damage that can occur following prolonged or repeated seizures. Gammaaminobutyric acid, the most common inhibitory neurotransmitter, usually suppresses seizure activity, although in absence seizure drugs that enhance GABA may exacerbate seizures. Experience with GABA indicates that certain neurotransmitters may have either anticonvulsant or proconvulsant effects depending on the neuronal networks involved. While other neurotransmitters also have effects on neuronal excitability, their function in epilepsy remains to be defined. © 1995 Wiley‐Liss, Inc.

Flexible Electrocorticography Electrode Array for Epileptiform Electrical Activity Recording under Glutamate and GABA Modulation on the Primary Somatosensory Cortex of Rats

“…With accumulation and spread of extracellular Glu, which destroys the balance of Glu absorption and release, inducing abnormal epileptiform activity, a rapid increase in power at 0–30 Hz is observed. After GABA injection, the power in each frequency band reduces significantly due to the inhibitory effect on neurons [ 36 , 37 ].…”

The GABAergic System and Endocannabinoids in Epilepsy and Seizures: What Can We Expect from Plant Oils?

“…GABA (γ-aminobutyric acid) and L-glutamate are the main inhibitory and excitatory neurotransmitters in the central nervous system (CNS), respectively, and both actively participate in epileptic disease [ 22 , 23 ]. However, the GABAergic system has been classically considered a main target of the anticonvulsant pharmacopeia, probably due to the high efficacy and potency of drugs acting on this system.…”

“…GABA activity is rapidly terminated at the synapse by reuptake into nerve terminals and is metabolized by a reaction catalyzed by GABA transaminase (GABA-T) involved in the regulation of the GABAergic system [ 30 , 31 ]. GABA is released as a neurotransmitter into the synaptic cleft in many brain areas when stimulated by depolarization and exerts its effects pre- and postsynaptically via ionotropic (GABA A ) and metabotropic (GABA B ) receptors [ 22 , 24 , 32 ]. Ionotropic receptors (GABA A s) trigger the opening of chloride channels, resulting in membrane hyperpolarization of postsynaptic cells [ 24 ], while GABA B receptors produce slow and prolonged inhibitory signals via G proteins and second messengers [ 33 ].…”

Venom-derived modulators of epilepsy-related ion channels

“…In the mammalian cortex, glutamate and γ-aminobutyric acid (GABA) are the most abundant excitatory and inhibitory neurotransmitters, respectively. Due to their ability to exert either excitatory or inhibitory effects on postsynaptic neurons, these neurotransmitters play a major modulatory role in brain excitability and, consequently, in epilepsy [33].…”