sphingosine-1-phosphate and Vasospasm--Intracranial

To demonstrate the relationship between of sphingosine-1-phosphate (S1P) expression and subarachnoid hemorrhage (SAH).. The basilar arteries from a "double-hemorrhage" rabbit model of SAH were used to investigate the relation between S1P expression and SAH. Various symptoms, including blood clots, basilar artery cross-sectional area, and S1P phosphatase expression were measured at day 3, 5, 7, 9.. The expression of S1P was enhanced in the cerebral vasospasm after subarachnoid hemorrhage in the rabbits. And S1P expression was consistent with the basilar artery cross-sectional area changes at day 3, 5, 7, 9.. Sphingosine-1-phosphate expression in the cerebral arterial may be a new indicator in the development of cerebral vasospasm after subarachnoid hemorrhage and provide a new therapeutic method for SAH.

Topics: Animals; Basilar Artery; Disease Models, Animal; Flow Cytometry; Lysophospholipids; Rabbits; Random Allocation; Sphingosine; Subarachnoid Hemorrhage; Time Factors; Vasospasm, Intracranial

The purpose of this study was to investigate changes in the cerebrospinal fluid sphingolipid profile in patients with subarachnoid hemorrhage in relation to the occurrence of symptomatic vasospasm and outcome at hospital discharge.. The ceramide profile in the cerebrospinal fluid was determined by mass spectrometry in control subjects and patients with Fisher 3 grade subarachnoid hemorrhage within 48 hours of the bleed. Patients were prospectively followed and subcategorized based on the occurrence of symptomatic vasospasm and modified Rankin Scale at discharge.. Compared to control subjects, patients with subarachnoid hemorrhage had higher cerebrospinal fluid levels of total ceramide (12.4±8.8 versus 54.6±49.3 pmol/mL; P<0.001). In the subgroup analysis, total ceramide levels in individuals with symptomatic vasospasm (104.2±57.0 pmol/mL) were higher than in those with asymptomatic vasospasm (32.4±25.7 pmol/mL; P=0.006) and no vasospasm (30.9±15.7 pmol/mL; P=0.003). In addition, compared to patients with a good outcome (modified Rankin Scale ≤3), individuals with poor outcome (modified Rankin Scale ≥4) had higher cerebrospinal fluid levels of total ceramide (79±25 versus 23±6 pmol/mL; P=0.008). When the relative contributions of the different ceramide species were calculated, a higher relative concentration of C(18:0) ceramide was observed in individuals with symptomatic vasospasm (P=0.018) and poor outcome (P=0.028).. Ceramide profile changes occur in subarachnoid hemorrhage. In this small case-based series elevation of levels of this sphingolipid, particularly C(18:0), was associated with the occurrence of symptomatic vasospasm and poor neurological outcome after subarachnoid hemorrhage.

Topics: Adult; Aged; Ceramides; Female; Humans; Lipids; Lysophospholipids; Male; Middle Aged; Predictive Value of Tests; Prognosis; Reference Standards; Sphingolipids; Sphingomyelin Phosphodiesterase; Sphingosine; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial

Inflammation has an important function in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH); however, the mediators of this inflammatory response have not been clearly identified. In this study, we have investigated the potential function of two sphingolipids, which occur naturally in plasma and serum, sphingosylphosphorylcholine (SPC) and sphingosine 1-phosphate (S1P), to act as proinflammatory mediators in cerebral artery vascular smooth muscle (VSM) cells. In rat cerebral arteries, SPC but not S1P activated p38 mitogen-activated protein kinase (MAPK). Using transcription factor arrays, two proinflammatory transcription factors activated by SPC in cerebral arteries were identified--nuclear factor-κB and CCAAT-enhancer-binding protein. Both these transcription factors were activated by SPC in a p38MAPK-dependent manner. To determine whether this contributed to vascular inflammation, an inflammatory protein array was performed, which showed that SPC increased release of the chemokine monocyte chemoattractant protein-1 (MCP-1) in cultured rat VSM cells. This increase in MCP-1 expression was confirmed in cerebral arteries. The S1P did not increase MCP-1 release. Taken together, our results suggest that SPC, but not S1P, can act as a proinflammatory mediator in cerebral arteries. This may contribute to inflammation observed after SAH and may be part of the initiating event in vasospasm.

Topics: Animals; Blood Platelets; Blotting, Western; Cells, Cultured; Cerebral Arteries; Chemokine CCL2; Electrophoretic Mobility Shift Assay; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Inflammation; Inflammation Mediators; Lysophospholipids; Male; Muscle, Smooth, Vascular; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylcholine; Rats; Rats, Sprague-Dawley; Sphingosine; Subarachnoid Hemorrhage; Transcription Factors; Up-Regulation; Vasospasm, Intracranial

Sphingosine 1-phosphate (S1P) is a platelet-derived bioactive lipid that exerts a variety of biological responses, including vasocontraction. To understand the involvement of S1P in cerebral vasospasm, we investigated the effect of S1P on vasocontraction of the canine basilar artery in vitro and in vivo.. We recorded isometric tension in basilar arterial rings from dogs in vitro and estimated time-course changes in the diameter of canine basilar arteries and the S1P concentration in cerebrospinal fluid (CSF) by angiography and radioreceptor assays, respectively, after administering S1P into the cisterna magna. Changes in the supernatant S1P concentration during clot formation were monitored by using the in vitro subarachnoid hemorrhage model, in which blood is mixed with CSF.. At concentrations ranging between 100 nmol/L and 10 micromol/L, S1P induced a dose-dependent contraction of the basilar artery in vitro. This effect was significantly inhibited by Y-27632, a highly selective Rho-kinase inhibitor. The administration of S1P into the CSF induced a 60% to 70% decrease in the arterial diameter within 15 minutes, and vasocontraction continued for 2 days thereafter. The concentration of S1P in the supernatant during clot formation in vitro reached approximately 300 nmol/L.. S1P induces vasocontraction in the canine basilar artery in vitro and in vivo, possibly through a mechanism involving activation of the Rho/Rho-kinase pathway. Thus, S1P might be considered as a novel spasmogenic substance involved in cerebral vasospasm after subarachnoid hemorrhage.

Topics: Amides; Animals; Basilar Artery; Blood; Cerebral Angiography; Cerebrospinal Fluid; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; In Vitro Techniques; Injections, Intraventricular; Intracellular Signaling Peptides and Proteins; Isometric Contraction; Lysophospholipids; Male; Protein Serine-Threonine Kinases; Pyridines; Radioligand Assay; rho-Associated Kinases; Sphingosine; Vascular Patency; Vasoconstriction; Vasospasm, Intracranial