Departments of Physiology and Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA.
Pediatr Res. 2023 Aug;94(2):495-502. doi: 10.1038/s41390-023-02486-5. Epub 2023 Jan 24.
Neonatal epileptic seizures cause postictal dysregulation of cerebral blood flow. Hydrogen sulfide (HS), a mediator with vasodilator and antioxidant properties, is produced in the brain by astrocyte cystathionine β-synthase (CBS). This study investigated whether HS improves the cerebral vascular outcome of seizures.
Epileptic seizures were induced in newborn pigs using bicuculline. The effects of the CBS inhibitor aminooxyacetate (AOA) and the HS donor NaHS on cerebral vascular outcome of seizures were examined in live pigs, cerebral endothelial cells, and cortical astrocytes.
Brain HS was elevated during seizures. AOA blocked HS and reduced functional hyperemia in the epileptic brain. The endothelium- and astrocyte-dependent vasodilation of pial arterioles was impaired 48 h after seizures suggesting cerebral vascular dysfunction. Systemic NaHS elevated brain HS and blocked reactive oxygen species in the epileptic brain and in primary endothelial cells and astrocytes during inflammatory and excitotoxic conditions. Postictal cerebrovascular dysfunction was exaggerated in HS-inhibited pigs and minimized in NaHS-treated pigs.
HS elevation in the epileptic brain via activation of CBS contributes to functional hyperemia and exhibits cerebroprotective properties. The HS donor NaHS enhances brain antioxidant defense and provides a therapeutic approach for preventing adverse cerebral vascular outcome of neonatal epileptic seizures.
Epileptic seizures in neonates lead to prolonged postictal cerebral vascular dysregulation. The role of hydrogen sulfide (HS), a mediator with vasodilator and antioxidant properties, in the epileptic brain has been explored. Astrocytes are major sites of enzymatic HS production in the epileptic brain. Postictal cerebral vascular dysfunction is exaggerated when astrocyte HS production is pharmacologically inhibited during seizures. Postictal cerebral vascular dysfunction is minimized when the brain HS is elevated by systemic administration of NaHS during seizures. NaHS provides a therapeutic approach for improving cerebrovascular outcome of epileptic seizures via a mechanism that involves the antioxidant potential of HS.
新生儿癫痫发作会导致发作后大脑血流调节紊乱。硫化氢（HS）是一种具有血管扩张和抗氧化特性的介质，由星形胶质细胞胱硫醚-β-合酶（CBS）在大脑中产生。本研究旨在探讨 HS 是否能改善癫痫发作时的脑血管预后。
使用荷包牡丹碱诱导新生猪癫痫发作。在活猪、脑内皮细胞和皮质星形胶质细胞中，观察 CBS 抑制剂氨基氧乙酸（AOA）和 HS 供体硫氢化钠（NaHS）对癫痫发作时脑血管预后的影响。
癫痫发作时大脑 HS 水平升高。AOA 阻断 HS 并减少癫痫大脑中的功能性充血。提示脑血管功能障碍，48 小时后，脑动静脉血管扩张受损。全身给予 NaHS 可升高大脑 HS 水平，并阻断癫痫大脑以及在炎症和兴奋毒性条件下的原代内皮细胞和星形胶质细胞中的活性氧。在 HS 抑制的猪中，发作后脑血管功能障碍加重，而在 NaHS 治疗的猪中则减轻。
通过 CBS 的激活，癫痫大脑中 HS 的升高有助于功能性充血，并表现出脑保护特性。HS 供体 NaHS 增强了大脑抗氧化防御能力，为预防新生儿癫痫发作后不良脑血管结局提供了一种治疗方法。
新生儿癫痫发作会导致发作后长时间的脑血管调节紊乱。本研究探索了具有血管扩张和抗氧化特性的介质硫化氢（HS）在癫痫大脑中的作用。在癫痫大脑中，星形胶质细胞是 HS 产生的主要部位。在癫痫发作时，通过药物抑制星形胶质细胞 HS 产生，会加重发作后脑血管功能障碍。在癫痫发作时，通过全身给予 NaHS 升高脑 HS 水平，可以减轻发作后脑血管功能障碍。NaHS 通过 HS 的抗氧化潜力来改善癫痫发作的脑血管预后。
