Using the immune system to target epilepsy.

Abstract

The sudden and transient disruption from normal brain function by the disordered, synchronous and rhythmic firing of populations of neurons or seizures is the common feature of a diverse collection of disease syndromes collectively called the epilepsies. The epilepsies are estimated to affect 1–2% of the population, with the most common form being temporal lobe epilepsy, which accounts for 40% of all types. The underlying cause of this form of epilepsy is thought to involve an imbalance in excitatory and inhibitory neurotransmission due to altered circuitry in the hippocampus resulting from the selective degeneration of hilar, CAI and CA3 pyramidal neurons but relative preservation of dentate granule neurons.39 Hyperexcitability in the hippocampus then occurs following synaptic reorganization of the surviving dentate granule cell mossy fiber axons into the inner molecular layer of the dentate gyrus. While surgical resection is useful in alleviating seizures, particularly for intractable temporal lobe epilepsy,38,24 pharmacotherapy is the mainstay of treatment for most forms. At the cellular level, anti-epileptic agents mediate their effects through three major pharmacological modes of actions: enhancement of inhibitory neurotransmission, attenuation of excitatory transmission or modulation of voltage-dependent ion channels. While the use of one or a combination of antiepileptic drugs can provide seizure control in most cases, there are also many cases refractory to treatment. Additionally, many of these compounds have been reported to negatively impact cognitive function,11 suggesting the continuing requirement for better and more specific treatments.KeywordsNMDA ReceptorStatus EpilepticusTemporal Lobe EpilepsyGlutamic Acid DecarboxylaseTemporal Lobe Epilepsy PatientThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.