NDLI: Role of the Sphingosine Metabolism Pathway on Neurons Against Experimental Cerebral Ischemia in Rats

Content Provider	Springer Nature Link
Author	Hasegawa, Yu Suzuki, Hidenori Altay, Orhan Rolland, William Zhang, John H.
Copyright Year	2013
Abstract	Although there is evidence that sphingosine-1-phosphate receptor-1 (S1P1) activation occurs following experimental brain injury, there is little information about its metabolic pathway in cerebral ischemia. The purpose of this study was to evaluate the role of the sphingosine metabolic pathway including S1P1 and sphingosine kinases 1 (SphK1) and 2 (SphK2) in transient middle cerebral artery occlusion (MCAO). Fifty-eight male Sprague–Dawley rats were used to assess temporal profiles of S1P1, SphK1, and SphK2 on neurons in infarct and periinfarct cortices at preinfarct state, 6 h, and 24 h after MCAO. The animals were then treated with vehicle and 0.25 mg/kg FTY720, which is an agonist of S1P receptors, and evaluated regarding neurological function, infarct volume, and S1P1 expression on neurons at 24 h after MCAO. The expressions of S1P1, SphK1, and SphK2 were significantly decreased after MCAO. Labeling of all markers was reduced in the infarct cortex but remained present in the periinfarct cortex and some were found to be on neurons. Significant improvements of neurological function and brain injury were observed in the FTY720 group compared with the vehicle and untreated groups, although S1P1 expression on neurons was reduced in the FTY720 group compared with the vehicle group. We demonstrated that S1P1, SphK1, and SphK2 were downregulated in the infarct cortex, whereas they were preserved in the periinfarct cortex where FTY720 reduced neuronal injury possibly via S1P1 activation. Our findings suggest that activation of the sphingosine metabolic pathway may be neuroprotective in cerebral ischemia.
Starting Page	524
Ending Page	532
Page Count	9
File Format	PDF
ISSN	18684483
Journal	Translational Stroke Research
Volume Number	4
Issue Number	5
e-ISSN	1868601X
Language	English
Publisher	Springer US
Publisher Date	2013-05-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Sphingosine 1-phosphate receptor-1 Sphingosine kinase 1 Sphingosine kinase 2 FTY720 Transient middle cerebral artery occlusion Neurosciences Neurology Cardiology Neurosurgery Vascular Surgery
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Neuroscience Neurology (clinical)

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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