Therapeutic potential of nitric oxide and its donors in hemorrhagic and ischemic stroke: a systematic review

Wang, Shijun#; Wan, Sicen#; Zhang, Xu#; Sun, Ming; Li, Hongru; Chen, Gang; Wang, Jiahe*; Li, Xiang Jr*

Author Information

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China

*Correspondence to: Jiahe Wang, MS, wangjiahe_96@163.com; Xiang Li Jr, MD, neurosurgerylee@163.com

#These authors contributed equally to this work.

Funding:This work was supported by Basic Research Pilot Project of Suzhou (No. SSD2024063), The Science and Education Foundation for Health of Suzhou for Youth (No. KJXW2023001), and Boxi Youth Natural Science Foundation (No. BXQN2023028).

Abstract

Nitric oxide is a gas molecule that serves as a signaling molecule in mammals, regulating the relaxation and contraction of vascular, thereby modulating local blood flow. Stroke encompasses both hemorrhagic and ischemic subtypes, with hemorrhagic strokes further classified into subarachnoid and intracerebral hemorrhages. The vasodilatory effects of nitric oxide and its derivatives have been confirmed in both peripheral and central vascular diseases. Additionally, animal studies have demonstrated that exogenous supplementation of nitric oxide or its donors has beneficial effects on stroke. We systematically reviewed the existing research on the relationship between nitric oxide donors and stroke, and elaborated on the pathophysiological processes in which nitric oxide is involved in different types of strokes. Given the significant differences in the concentration and temporal effects of nitric oxide in various types of strokes and their pathophysiological processes, the optimal timing for exogenous nitric oxide intervention under different conditions was analyzed to enhance clinical awareness regarding the treatment with nitric oxide and its donors. Future research can place greater emphasis on the development of novel nitric oxide donors and their diverse administration routes to further optimize treatment outcomes for stroke. This review underscores the limited progress in the clinical translation of nitric oxide-based therapeutics and aims to offer novel insights for the further optimization of their development, delivery strategies, and administration timing.

摘要

一氧化氮是一种气体分子，在哺乳动物中作为信号分子，调节血管的舒张与收缩，从而调控局部血流量。卒中包括出血性和缺血性两种亚型，其中出血性卒中进一步分为蛛网膜下腔出血和脑内出血。一氧化氮及其衍生物的血管舒张效应已在周围和中枢血管疾病中得到证实。此外，动物研究表明，外源性补充一氧化氮或其供体对卒中具有有益作用。我们系统回顾了现有关于一氧化氮供体与卒中关系的研究，并阐述了一氧化氮在不同类型卒中中所参与的病理生理过程。鉴于一氧化氮在不同类型卒中及其病理生理过程中的浓度和时间效应存在显著差异，本文分析了不同情况下外源性一氧化氮干预的最佳时机，以提高临床对一氧化氮及其供体治疗的认识。未来的研究可更加注重新型一氧化氮供体的开发及其多样化的给药途径，以进一步优化卒中的治疗效果。本综述强调了基于一氧化氮的疗法在临床转化方面进展有限，并旨在为其开发、递送策略及给药时机的进一步优化提供新的思路。