FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3105032904> ?p ?o ?g. }

• W3105032904 abstract "ABSTRACT Blood brain barrier (BBB) dysfunction upon ischemia and hypoxia has been implicated in the exacerbation of neuronal injury in stroke. Despite the therapeutic potential of the cerebrovascular endothelium, the limited understanding of the endothelial signaling pathways governing BBB function restricts progress towards developing novel therapeutic approaches specifically targeting the endothelium. Sphingosine-1-phosphate (S1P) is a potent modulator of endothelial function via its receptors (S1PR). Recent human and mouse studies indicate that vasoprotective endothelial S1P signaling via S1PR1 may be impaired in cardiovascular and inflammatory diseases. Herein, we investigated the expression of S1PR1 in the mouse and human cerebrovascular endothelium and the role of endothelial-specific S1PR1 signaling in brain injury in a mouse model of aneurysmal subarachnoid hemorrhage (SAH), the most devastating type of stroke. We found that S1PR1 is the most abundant S1PR transcript in the mouse brain and in mouse and human brain endothelial cells (20-100 mRNA copies per cell). S1PR1 transcripts were significantly enriched (~6 fold) in mouse cortical microvessels compared to total brain. Using the S1PR1-eGFP knock in mouse, we found that S1PR1-eGFP is abundantly expressed in the cerebrovascular endothelium in the mouse brain. A similar pattern of expression was observed in human brain samples. Endothelial specific deletion of S1PR1 in adult mice ( S1pr1 flox/flox xCdh5-Cre ERT2 , referred to as S1pr1 iECKO ), resulted in exacerbation of brain edema, neuronal injury and worsened neurological outcomes upon SAH compared to S1pr1 flox/flox littermates. No differences in the subarachnoid blood, hemostasis or cerebral blood flow changes during and after SAH were found between groups. Mechanistically, S1pr1 iECKO exhibited aggravated BBB dysfunction and increased phosphorylation of myosin light chain (MLC) in isolated cortical microvessels, a downstream effector of the Rho-ROCK pathway implicated in endothelial inflammation and barrier dysfunction. Taken together, our data indicate that S1PR1 is an endogenous protective signaling pathway in the endothelium, critical to maintain BBB function and to mitigate neuronal injury in pathological conditions. Thus, the therapeutic and diagnostic potential of the endothelial sphingosine-1-phosphate pathway in stroke deserves further study." @default.
• W3105032904 created "2020-11-23" @default.
• W3105032904 creator A5002902942 @default.
• W3105032904 creator A5018107869 @default.
• W3105032904 creator A5030829514 @default.
• W3105032904 creator A5035231990 @default.
• W3105032904 creator A5039011294 @default.
• W3105032904 creator A5048492327 @default.
• W3105032904 creator A5058899441 @default.
• W3105032904 creator A5066602980 @default.
• W3105032904 creator A5068297370 @default.
• W3105032904 creator A5074615107 @default.
• W3105032904 creator A5090356821 @default.
• W3105032904 date "2018-06-28" @default.
• W3105032904 modified "2023-10-14" @default.
• W3105032904 title "Endothelial sphingosine-1-phosphate receptor 1 deficiency exacerbates brain injury and blood brain barrier dysfunction upon subarachnoid hemorrhage in mice" @default.
• W3105032904 cites W122155702 @default.
• W3105032904 cites W127046385 @default.
• W3105032904 cites W1493585689 @default.
• W3105032904 cites W1804985370 @default.
• W3105032904 cites W1910276728 @default.
• W3105032904 cites W1955736456 @default.
• W3105032904 cites W1963535811 @default.
• W3105032904 cites W1965836316 @default.
• W3105032904 cites W1967076681 @default.
• W3105032904 cites W1969448383 @default.
• W3105032904 cites W1972357850 @default.
• W3105032904 cites W1974297564 @default.
• W3105032904 cites W1979620916 @default.
• W3105032904 cites W1979799609 @default.
• W3105032904 cites W1980406902 @default.
• W3105032904 cites W1984179269 @default.
• W3105032904 cites W1986426214 @default.
• W3105032904 cites W1987859643 @default.
• W3105032904 cites W1992495544 @default.
• W3105032904 cites W1992758695 @default.
• W3105032904 cites W1992981081 @default.
• W3105032904 cites W1994679471 @default.
• W3105032904 cites W1995037165 @default.
• W3105032904 cites W2000422049 @default.
• W3105032904 cites W2000965529 @default.
• W3105032904 cites W2001741720 @default.
• W3105032904 cites W2006985918 @default.
• W3105032904 cites W2007878869 @default.
• W3105032904 cites W2009021880 @default.
• W3105032904 cites W2009065888 @default.
• W3105032904 cites W2010033467 @default.
• W3105032904 cites W2011398156 @default.
• W3105032904 cites W2015541518 @default.
• W3105032904 cites W2019209482 @default.
• W3105032904 cites W2019889454 @default.
• W3105032904 cites W2020844847 @default.
• W3105032904 cites W2026629766 @default.
• W3105032904 cites W2026796826 @default.
• W3105032904 cites W2028514452 @default.
• W3105032904 cites W2029417795 @default.
• W3105032904 cites W2030613585 @default.
• W3105032904 cites W2031762899 @default.
• W3105032904 cites W2034275438 @default.
• W3105032904 cites W2035176010 @default.
• W3105032904 cites W2035569448 @default.
• W3105032904 cites W2040981235 @default.
• W3105032904 cites W2043112660 @default.
• W3105032904 cites W2043175847 @default.
• W3105032904 cites W2044310963 @default.
• W3105032904 cites W2045733139 @default.
• W3105032904 cites W2048085891 @default.
• W3105032904 cites W2048766205 @default.
• W3105032904 cites W2049384154 @default.
• W3105032904 cites W2054022839 @default.
• W3105032904 cites W2056856515 @default.
• W3105032904 cites W2060298694 @default.
• W3105032904 cites W2063858338 @default.
• W3105032904 cites W2065284939 @default.
• W3105032904 cites W2069434477 @default.
• W3105032904 cites W2069634387 @default.
• W3105032904 cites W2071561174 @default.
• W3105032904 cites W2072001685 @default.
• W3105032904 cites W2082004477 @default.
• W3105032904 cites W2084969545 @default.
• W3105032904 cites W2085945520 @default.
• W3105032904 cites W2091399990 @default.
• W3105032904 cites W2092814331 @default.
• W3105032904 cites W2093984243 @default.
• W3105032904 cites W2095928634 @default.
• W3105032904 cites W2103164849 @default.
• W3105032904 cites W2104205655 @default.
• W3105032904 cites W2104948944 @default.
• W3105032904 cites W2106361045 @default.
• W3105032904 cites W2107325549 @default.
• W3105032904 cites W2116525638 @default.
• W3105032904 cites W2118606956 @default.
• W3105032904 cites W2120695828 @default.
• W3105032904 cites W2124077349 @default.
• W3105032904 cites W2125036060 @default.
• W3105032904 cites W2126232301 @default.
• W3105032904 cites W2126394436 @default.
• W3105032904 cites W2129034760 @default.
• W3105032904 cites W2137299577 @default.
• W3105032904 cites W2137571200 @default.

• next