Aggravation of Seizure-like Events by Hydrogen Sulfide: Involvement of Multiple Targets that Control Neuronal Excitability

Aims Epileptic 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 Results Pentylenetetrazole (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. Conclusions These 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.