Possible alterations in GABAAreceptor signaling that underlie benzodiazepine-resistant seizures

摘要: Benzodiazepines have been used for decades as first-line treatment status epilepticus (SE). For reasons that are not fully understood, the efficacy of benzodiazepines decreases with increasing duration seizure activity. This often forces clinicians to resort more drastic second- and third-line treatments always successful. The antiseizure properties mediated by γ-aminobutyric acid type A (GABA(A) ) receptors. Decades research focused on failure GABAergic inhibition after onset likely cause development benzodiazepine resistance during SE. However, details deficits in GABA(A) signaling still largely unknown. Therefore, it is necessary improve our understanding mechanisms so effective strategies can be formulated. In this review we discuss evidence supporting role altered receptor function major underlying benzodiazepine-resistant SE both humans animal models. We specifically address prevailing hypothesis, which based changes number subtypes receptors, well potential influence perturbed chloride homeostasis mature brain.