ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2014
Hypoxia/reoxygenation stress signals an increase in organic anion transporting polypeptide 1a4 (Oatp1a4) at the blood-brain barrier: relevance to CNS drug delivery.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 71 citations in OpenAlex.
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- The Basic Requirement of Tight Junction Proteins in Blood-Brain Barrier Function and Their Role in Pathologies.International journal of molecular sciences · 2024Review
- CNS Drug Delivery in Stroke: Improving Therapeutic Translation From the Bench to the Bedside.Stroke · 2024Review
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- Methods to Study Drug Uptake at the Blood-Brain Barrier Following Experimental Ischemic Stroke: In Vitro and In Vivo Approaches.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Targeting organic cation transporters at the blood-brain barrier to treat ischemic stroke in rats.Experimental neurology · 2022Article
- Statins as antiepileptogenic drugs: Analyzing the evidence and identifying the most promising statin.Epilepsia · 2022Review
- Transport Mechanisms at the Blood-Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs.Pharmaceutics · 2022Review
- Regulation of Blood-Brain Barrier Transporters by Transforming Growth Factor-Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- A Historical Review of Brain Drug Delivery.Pharmaceutics · 2022Review
- Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs).Pharmaceutics · 2022Review
- High-Dose Acetaminophen Alters the Integrity of the Blood-Brain Barrier and Leads to Increased CNS Uptake of Codeine in Rats.Pharmaceutics · 2022Article
- Current Chemical, Biological, and Physiological Views in the Development of Successful Brain-Targeted Pharmaceutics.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Blood-Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke.International journal of molecular sciences · 2022Review
- Histopathological, histochemical and biochemical postmortem changes in induced fatal hypothermia in rats.Forensic sciences research · 2022Article
- Dexamethasone enhances the efficacy of atorvastatin in inhibiting excessively inflammation-induced abnormal angiogenesis by regulating macrophages.Journal of neuroinflammation · 2021Article
- Disease-Induced Modulation of Drug Transporters at the Blood-Brain Barrier Level.International journal of molecular sciences · 2021Review
- Transport Properties of Statins by Organic Anion Transporting Polypeptide 1A2 and Regulation by Transforming Growth Factor-The Journal of pharmacology and experimental therapeutics · 2021Article
- Regulation of blood-brain barrier integrity by microglia in health and disease: A therapeutic opportunity.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Review
- Probing the drug delivery strategies in ischemic stroke therapy.Drug delivery · 2020Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Cerebral hypoxia and subsequent reoxygenation stress (H/R) is a component of several diseases. One approach that may enable neural tissue rescue after H/R is central nervous system (CNS) delivery of drugs with brain protective effects such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (i.e., statins). Our present in vivo data show that atorvastatin, a commonly prescribed statin, attenuates poly (ADP-ribose) polymerase (PARP) cleavage in the brain after 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 organic anion transporting polypeptide 1a4 (Oatp1a4) at the BBB under H/R conditions. In rat brain microvessels, H/R (6% O2, 60 minutes followed by 21% O2, 10 minutes) increased Oatp1a4 expression. Brain uptake of taurocholate (i.e., Oap1a4 probe substrate) and atorvastatin were reduced by Oatp inhibitors (i.e., estrone-3-sulfate and fexofenadine), suggesting involvement of Oatp1a4 in brain drug delivery. Pharmacological inhibition of transforming growth factor-β (TGF-β)/activin receptor-like kinase 5 (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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.