Abstract：
The triggers of status epilepticus (SE) in non-epileptic patients can vary widely, from idiopathic causes to exposure to chemoconvulsants. Regardless of its etiology, prolonged SE can cause significant brain damage, commonly resulting in the development of epilepsy, which is often accompanied by increased anxiety. GABAA receptor (GABAAR)-mediated inhibition has a central role among the mechanisms underlying brain damage and the ensuing epilepsy and anxiety. During SE, calcium influx primarily via ionotropic glutamate receptors activates signaling cascades which trigger a rapid internalization of synaptic GABAARs; this weakens inhibition, exacerbating seizures and excitotoxicity. GABAergic interneurons are more susceptible to excitotoxic death than principal neurons. During the latent period of epileptogenesis, the aberrant reorganization in synaptic interactions that follow interneuronal loss in injured brain regions, leads to the formation of hyperexcitable, seizurogenic neuronal circuits, along with disturbances in brain oscillatory rhythms. Reduction in the spontaneous, rhythmic \"bursts\" of IPSCs in basolateral amygdala neurons is likely to play a central role in anxiogenesis. Protecting interneurons during SE is key to preventing both epilepsy and anxiety. Antiglutamatergic treatments, including antagonism of calcium-permeable AMPA receptors, can be expected to control seizures and reduce excitotoxicity not only by directly suppressing hyperexcitation, but also by counteracting the internalization of synaptic GABAARs. Benzodiazepines, as delayed treatment of SE, have low efficacy due to the reduction and dispersion of their targets (the synaptic GABAARs), but also because themselves contribute to further reduction of available GABAARs at the synapse; furthermore, benzodiazepines may be completely ineffective in the immature brain.
摘要：
非癫痫患者癫痫持续状态（SE）的触发因素可能差异很大，从特发性原因到接触化学惊厥药。不管它的病因是什么,长时间的SE会导致严重的脑损伤，通常导致癫痫的发展，这往往伴随着焦虑的增加。GABAA受体（GABAAR）介导的抑制在脑损伤和随后的癫痫和焦虑的潜在机制中具有核心作用。在SE期间,钙内流主要通过离子型谷氨酸受体激活信号级联，触发突触GABAAR的快速内化;这减弱抑制，加重癫痫发作和兴奋性毒性。GABA能中间神经元比主要神经元更容易发生兴奋性毒性死亡。在癫痫发生的潜伏期，在受损脑区神经元间丢失后突触相互作用的异常重组，导致过度兴奋的形成，引起尿源性神经元回路的癫痫发作,伴随着大脑振荡节律的紊乱。在自发的减少，基底外侧杏仁核神经元中IPSC的节律性“爆发”可能在焦虑发生中起重要作用。在SE期间保护中间神经元是预防癫痫和焦虑的关键。抗谷氨酸治疗，包括钙通透性AMPA受体的拮抗作用，不仅可以通过直接抑制兴奋来控制癫痫发作和减少兴奋性毒性，而且还通过抵消突触GABAAR的内化。苯二氮卓类药物,作为SE的延迟治疗，由于其靶标（突触GABAAR）的减少和分散，但也因为它们本身有助于进一步减少突触处可用的GABAAR；此外，苯二氮卓类药物在未成熟的大脑中可能完全无效。
