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Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats.
Stroke. 2010 Feb; 41(2):368-74.S

Abstract

BACKGROUND AND PURPOSE

FTY720 is a known sphingosine 1-phosphate receptor agonist. In the present study, we investigated the neuroprotective effect of postischemic administration of FTY720 in rats with 2 hours transient middle cerebral artery occlusion (MCAO).

METHODS

One hundred eleven male rats were randomly assigned to sham-operated and MCAO treated with vehicle, 0.25 mg/kg and 1 mg/kg of FTY720, another selective sphingosine 1-phosphate receptor-1 agonist SEW2871 (5 mg/kg), or 0.25 mg/kg of FTY720 plus a sphingosine 1-phosphate antagonist, VPC23019 (0.5 mg/kg). Drugs were injected intraperitoneally immediately after reperfusion. Neurological score and infarct volume were assessed at 24 and 72 hours after MCAO. Western blotting, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling were conducted at 24 hours after MCAO.

RESULTS

FTY720 significantly reduced infarct volume and improved neurological score at 24 and 72 hours after MCAO compared with the vehicle group. SEW2871 showed similar neuroprotective effects to FTY720, whereas VPC 20319 abolished the neuroprotective effects of FTY720. FTY720 significantly retained Akt and extracellular signal-regulated kinase phosphorylation and Bcl-2 expression and decreased cleaved caspase-3 expression and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling-positive neurons at 24 hours after MCAO. VPC23019 blocked the antiapoptotic effects of FTY720.

CONCLUSIONS

These data suggest that activation of sphingosine 1-phosphate-1 by FTY720 reduces neuronal death after transient MCAO.

Authors+Show Affiliations

Department of Physiology, Loma Linda University School of Medicine, Loma Linda, Calif 92354, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19940275

Citation

Hasegawa, Yu, et al. "Activation of Sphingosine 1-phosphate Receptor-1 By FTY720 Is Neuroprotective After Ischemic Stroke in Rats." Stroke, vol. 41, no. 2, 2010, pp. 368-74.
Hasegawa Y, Suzuki H, Sozen T, et al. Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats. Stroke. 2010;41(2):368-74.
Hasegawa, Y., Suzuki, H., Sozen, T., Rolland, W., & Zhang, J. H. (2010). Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats. Stroke, 41(2), 368-74. https://doi.org/10.1161/STROKEAHA.109.568899
Hasegawa Y, et al. Activation of Sphingosine 1-phosphate Receptor-1 By FTY720 Is Neuroprotective After Ischemic Stroke in Rats. Stroke. 2010;41(2):368-74. PubMed PMID: 19940275.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats. AU - Hasegawa,Yu, AU - Suzuki,Hidenori, AU - Sozen,Takumi, AU - Rolland,William, AU - Zhang,John H, Y1 - 2009/11/25/ PY - 2009/11/27/entrez PY - 2009/11/27/pubmed PY - 2010/2/24/medline SP - 368 EP - 74 JF - Stroke JO - Stroke VL - 41 IS - 2 N2 - BACKGROUND AND PURPOSE: FTY720 is a known sphingosine 1-phosphate receptor agonist. In the present study, we investigated the neuroprotective effect of postischemic administration of FTY720 in rats with 2 hours transient middle cerebral artery occlusion (MCAO). METHODS: One hundred eleven male rats were randomly assigned to sham-operated and MCAO treated with vehicle, 0.25 mg/kg and 1 mg/kg of FTY720, another selective sphingosine 1-phosphate receptor-1 agonist SEW2871 (5 mg/kg), or 0.25 mg/kg of FTY720 plus a sphingosine 1-phosphate antagonist, VPC23019 (0.5 mg/kg). Drugs were injected intraperitoneally immediately after reperfusion. Neurological score and infarct volume were assessed at 24 and 72 hours after MCAO. Western blotting, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling were conducted at 24 hours after MCAO. RESULTS: FTY720 significantly reduced infarct volume and improved neurological score at 24 and 72 hours after MCAO compared with the vehicle group. SEW2871 showed similar neuroprotective effects to FTY720, whereas VPC 20319 abolished the neuroprotective effects of FTY720. FTY720 significantly retained Akt and extracellular signal-regulated kinase phosphorylation and Bcl-2 expression and decreased cleaved caspase-3 expression and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling-positive neurons at 24 hours after MCAO. VPC23019 blocked the antiapoptotic effects of FTY720. CONCLUSIONS: These data suggest that activation of sphingosine 1-phosphate-1 by FTY720 reduces neuronal death after transient MCAO. SN - 1524-4628 UR - https://www.unboundmedicine.com/medline/citation/19940275/Activation_of_sphingosine_1_phosphate_receptor_1_by_FTY720_is_neuroprotective_after_ischemic_stroke_in_rats_ L2 - http://www.ahajournals.org/doi/full/10.1161/STROKEAHA.109.568899?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -