Sphingosine-1-phosphate Signalling in Aneurysmal Subarachnoid Haemorrhage: Basic Science to Clinical Translation.

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• Sphingosine-1-phosphate (S1P) is a lipid mediator primarily acting extracellularly via S1P receptors.
• The S1P signaling pathway is increasingly recognized for its role in neurological disorders, including injury following aneurysmal subarachnoid hemorrhage (aSAH).

Purpose of the Study:

• To review and synthesize current knowledge on the role of S1P in neurological injury after aSAH.
• To reconcile conflicting findings regarding S1P's effects on brain parenchyma.
• To explore the therapeutic potential of S1P receptor modulators for aSAH.

Main Methods:

• Comprehensive literature review of studies investigating S1P in the context of aSAH.
• Analysis of data on S1P levels in cerebrospinal fluid and its association with cerebral vasospasm.
• Evaluation of research on S1P's impact on brain parenchyma, considering both beneficial and detrimental effects.

Main Results:

• S1P levels demonstrably rise in cerebrospinal fluid post-aSAH, correlating with cerebral artery vasospasm.
• The precise role of S1P within the brain parenchyma following aSAH remains controversial, with evidence supporting both protective and damaging effects.
• S1P receptor modulators, currently approved for multiple sclerosis treatment, are potential candidates for repurposing in aSAH management.

Conclusions:

• A unified interpretation of S1P's dual role in aSAH pathophysiology is proposed.
• Repurposing S1P receptor modulators presents a promising therapeutic avenue for aSAH.
• Significant knowledge gaps persist regarding human S1P signaling post-aSAH, necessitating further research and careful clinical consideration for pathway targeting.