Aggravation of Seizure-like Events by Hydrogen Sulfide: Involvement of Multiple Targets that Control Neuronal Excitability
Aggravation of Seizure-like Events by Hydrogen Sulfide: Involvement of Multiple Targets that Control Neuronal Excitability
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DOI：
10.1111/cns.12228
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发表时间：
2014-05-01
影响因子：
5.5
通讯作者：
Chen, Jian-Guo
中科院分区：
文献类型：
--
作者：
Luo, Yi;Wu, Peng-Fei;Chen, Jian-Guo
癫痫发作是脑卒中后常见的神经系统并发症，发生率为3%。然而，癫痫发作与中风的内在相关性在很大程度上仍然未知。硫化氢（H2S）是一种可介导脑缺血损伤的气体递质。但H2S在癫痫发作中的作用尚未被理解。我们研究了硫化氢对类癫痫事件（SLEs）和相关mechanism.Methods和Results戊四唑（PTZ）和匹罗卡品诱导的大鼠癫痫发作模型的影响。采用膜片钳技术观察了低Mg ~（2+）/高K ~+和4-氨基吡啶（4-AP）诱导的癫痫发作模型。结果表明，NaHS可加重PTZ和匹罗卡品诱导的SLE，而NaHS可加重低Mg ~（2+）/高K ~+和4-AP诱导的SLE，这可能与NaHS对电压门控钠通道、N-甲基-D-天冬氨酸受体（NMDAR）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）功能的调节有关。此外，这些影响被逆转，通过阻断电压门控钠通道，NMDAR，和AMPAR.ConclusionsThese结果表明，在SLE在体内和体外的H2S水平增加的病理作用。控制H2S生物合成的酶可能是脑卒中后癫痫治疗中抗癫痫策略的有趣靶点。
AimsEpileptic seizures are well-known neurological complications following stroke, occurring in 3% of patients. However, the intrinsic correlation of seizures with stroke remains largely unknown. Hydrogen sulfide (H2S) is a gas transmitter that may mediate cerebral ischemic injury. But the role of H2S in seizures has not been understood yet. We examined the effect of H2S on seizure-like events (SLEs) and underlying mechanisms.Methods and ResultsPentylenetetrazole (PTZ)- and pilocarpine-induced rat epileptic seizure models were tested. Low-Mg2+/high-K+- and 4-aminopyridine (4-AP)-induced epileptic seizure models were examined using patch-clamp recordings in brain slices. It was found that NaHS aggravated both PTZ- and pilocarpine-induced SLEs in rats, while both low-Mg2+/high-K+- and 4-AP-induced SLEs were also exacerbated by NaHS in brain slices, which may be due to its regulation on the voltage-gated sodium channel, N-methyl-D-aspartic acid receptor (NMDAR), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) function. Furthermore, these effects were reversed by blocking voltage-gated sodium channel, NMDAR, and AMPAR.ConclusionsThese results suggest a pathological role of increased H2S level in SLEs in vivo and in vitro. Enzymes that control H2S biosynthesis could be interesting targets for antiepileptic strategies in poststroke epilepsy treatment.