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• W103663516 abstract "Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events in neurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for treatment of acute ischemia/reperfusion injury, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can salvageable brain tissue and/or protect BBB integrity during cerebral hypoxia and subsequent reoxygenation stress (H/R). One approach that may enable neural tissue rescue following H/R is CNS delivery of drugs with brain protective effects such as HMG-CoA reductase inhibitors (i.e., statins). Our present in vivo data demonstrates that atorvastatin, a commonly prescribed statin, attenuates poly (ADP-ribose) polymerase (PARP) cleavage in the brain following H/R, suggesting neuroprotective efficacy. However, atorvastatin use as a CNS therapeutic is limited by poor blood-brain barrier (BBB) penetration. Therefore, we examined regulation and functional expression of the known statin transporter Oatp1a4 at the BBB under H/R conditions. In rat brain microvessels H/R (6% O₂, 60 min followed by 21% O₂, 10 min) increased Oatp1a4 expression. Brain uptake of taurocholate (i.e., Oap1a4 probe substrate) and atorvastatin were reduced by Oatp inhibitors (i.e., estrone-3-sulfate, fexofenadine), suggesting involvement of Oatp1a4 in brain drug delivery. Pharmacological inhibition of TGF-β/ALK5 signaling with the selective inhibitor SB431542 increased Oatp1a4 functional expression, suggesting a role for TGF-β/ALK5 signaling in Oatp1a4 regulation. Taken together, our novel data show that targeting an endogenous BBB drug uptake transporter (i.e., Oatp1a4) may be a viable approach for optimizing CNS drug delivery for treatment of diseases with an H/R component." @default.
• W103663516 created "2016-06-24" @default.
• W103663516 creator A5074834797 @default.
• W103663516 date "2014-01-01" @default.
• W103663516 modified "2023-09-27" @default.
• W103663516 title "Hypoxia/Reoxygenation Stress Modulates Atorvastatin Transport at the Blood-Brain Barrier: A Role for Organic Anion Transporting Polypeptide" @default.
• W103663516 cites W131661586 @default.
• W103663516 cites W1516536009 @default.
• W103663516 cites W1532944255 @default.
• W103663516 cites W1553061387 @default.
• W103663516 cites W1598081091 @default.
• W103663516 cites W1601678499 @default.
• W103663516 cites W1637334016 @default.
• W103663516 cites W1664986234 @default.
• W103663516 cites W1675006565 @default.
• W103663516 cites W1714678118 @default.
• W103663516 cites W1882050418 @default.
• W103663516 cites W1964471078 @default.
• W103663516 cites W1965489478 @default.
• W103663516 cites W1969116648 @default.
• W103663516 cites W1969738474 @default.
• W103663516 cites W1969794746 @default.
• W103663516 cites W1971442835 @default.
• W103663516 cites W1976148567 @default.
• W103663516 cites W1976169273 @default.
• W103663516 cites W1976994600 @default.
• W103663516 cites W1979800084 @default.
• W103663516 cites W1980869901 @default.
• W103663516 cites W1982355800 @default.
• W103663516 cites W1982877190 @default.
• W103663516 cites W1983348654 @default.
• W103663516 cites W1988492326 @default.
• W103663516 cites W1991091534 @default.
• W103663516 cites W1992495728 @default.
• W103663516 cites W1993191156 @default.
• W103663516 cites W1994892692 @default.
• W103663516 cites W1995629926 @default.
• W103663516 cites W1996697333 @default.
• W103663516 cites W1996989104 @default.
• W103663516 cites W1998275215 @default.
• W103663516 cites W1999959667 @default.
• W103663516 cites W2000351290 @default.
• W103663516 cites W2002269747 @default.
• W103663516 cites W2002751444 @default.
• W103663516 cites W2003633558 @default.
• W103663516 cites W2003696679 @default.
• W103663516 cites W2010711249 @default.
• W103663516 cites W2011554900 @default.
• W103663516 cites W2012582908 @default.
• W103663516 cites W2014856474 @default.
• W103663516 cites W2015283800 @default.
• W103663516 cites W2017665309 @default.
• W103663516 cites W2017702989 @default.
• W103663516 cites W2018954111 @default.
• W103663516 cites W2020757356 @default.
• W103663516 cites W2024679475 @default.
• W103663516 cites W2029645827 @default.
• W103663516 cites W2032150209 @default.
• W103663516 cites W2035411579 @default.
• W103663516 cites W2035653659 @default.
• W103663516 cites W2036736823 @default.
• W103663516 cites W2037388690 @default.
• W103663516 cites W2041295155 @default.
• W103663516 cites W2042996709 @default.
• W103663516 cites W2044401686 @default.
• W103663516 cites W2044770099 @default.
• W103663516 cites W2044813154 @default.
• W103663516 cites W2046141417 @default.
• W103663516 cites W2047230924 @default.
• W103663516 cites W2050897300 @default.
• W103663516 cites W2051010051 @default.
• W103663516 cites W2051214272 @default.
• W103663516 cites W2051709012 @default.
• W103663516 cites W2053292669 @default.
• W103663516 cites W2053608702 @default.
• W103663516 cites W2054129577 @default.
• W103663516 cites W2058728855 @default.
• W103663516 cites W2059253659 @default.
• W103663516 cites W2061254404 @default.
• W103663516 cites W2064385602 @default.
• W103663516 cites W2065206396 @default.
• W103663516 cites W2066123672 @default.
• W103663516 cites W2066681478 @default.
• W103663516 cites W2068892466 @default.
• W103663516 cites W2069070477 @default.
• W103663516 cites W2069664695 @default.
• W103663516 cites W2070013537 @default.
• W103663516 cites W2070168780 @default.
• W103663516 cites W2072093696 @default.
• W103663516 cites W2072451175 @default.
• W103663516 cites W2074554971 @default.
• W103663516 cites W2074983104 @default.
• W103663516 cites W2075590617 @default.
• W103663516 cites W2075877825 @default.
• W103663516 cites W2078215490 @default.
• W103663516 cites W2081574942 @default.
• W103663516 cites W2081680109 @default.
• W103663516 cites W2081808464 @default.
• W103663516 cites W2082617426 @default.
• W103663516 cites W2084370109 @default.

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