Faculty of Medicine, University of Southampton, Southampton, SO17 1BJ, UK.
Department of Neurosurgery, Wessex Neurological Centre, University Hospital Southampton, Southampton, SO16 6YD, UK.
Transl Stroke Res. 2024 Apr;15(2):352-363. doi: 10.1007/s12975-023-01133-9. Epub 2023 Feb 7.
Sphingosine-1-phosphate (S1P) is generated intracellularly and, when transported to the extracellular compartment, predominantly signals through S1P receptors. The S1P signalling pathway has been implicated in the pathophysiology of neurological injury following aneurysmal subarachnoid haemorrhage (aSAH). In this review, we bring together all the available data regarding the role of S1P in neurological injury following aSAH. There is agreement in the literature that S1P increases in the cerebrospinal fluid following aSAH and leads to cerebral artery vasospasm. On the other hand, the role of S1P in the parenchyma is less clear cut, with different studies arguing for beneficial and deleterious effects. A parsimonious interpretation of this apparently conflicting data is presented. We discuss the potential of S1P receptor modulators, in clinical use for multiple sclerosis, to be repurposed for aSAH. Finally, we highlight the gaps in our knowledge of S1P signalling in humans, the clinical challenges of targeting the S1P pathway after aSAH and other research priorities.
鞘氨醇-1-磷酸（S1P）在细胞内产生，当运输到细胞外区室时，主要通过 S1P 受体发出信号。S1P 信号通路与蛛网膜下腔出血（aSAH）后神经损伤的病理生理学有关。在这篇综述中，我们汇集了所有关于 S1P 在 aSAH 后神经损伤中的作用的现有数据。文献中一致认为，S1P 在 aSAH 后脑脊液中增加，并导致脑动脉血管痉挛。另一方面，S1P 在实质中的作用不太明确，不同的研究提出了有益和有害的作用。我们对这些明显矛盾的数据提出了一种简单的解释。我们讨论了 S1P 受体调节剂的潜力，这些调节剂在多发性硬化症的临床应用中可能被重新用于 aSAH。最后，我们强调了我们对人类 S1P 信号的知识空白、在 aSAH 后靶向 S1P 通路的临床挑战以及其他研究重点。
