|Title||Blood-Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Nilles KL, Williams EI, Betterton RD, Davis TP, Ronaldson PT|
|Journal||Int J Mol Sci|
|Date Published||2022 Feb 08|
|Keywords||Animals, Blood-Brain Barrier, Disease Models, Animal, Gene Expression Regulation, Humans, Ischemic Stroke, Molecular Targeted Therapy, Neuroprotective Agents, Organic Anion Transporters, Organic Cation Transport Proteins|
Globally, stroke is a leading cause of death and long-term disability. Over the past decades, several efforts have attempted to discover new drugs or repurpose existing therapeutics to promote post-stroke neurological recovery. Preclinical stroke studies have reported successes in identifying novel neuroprotective agents; however, none of these compounds have advanced beyond a phase III clinical trial. One reason for these failures is the lack of consideration of blood-brain barrier (BBB) transport mechanisms that can enable these drugs to achieve efficacious concentrations in ischemic brain tissue. Despite the knowledge that drugs with neuroprotective properties (i.e., statins, memantine, metformin) are substrates for endogenous BBB transporters, preclinical stroke research has not extensively studied the role of transporters in central nervous system (CNS) drug delivery. Here, we review current knowledge on specific BBB uptake transporters (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents); organic cation transporters (OCTs in humans; Octs in rodents) that can be targeted for improved neuroprotective drug delivery. Additionally, we provide state-of-the-art perspectives on how transporter pharmacology can be integrated into preclinical stroke research. Specifically, we discuss the utility of in vivo stroke models to transporter studies and considerations (i.e., species selection, co-morbid conditions) that will optimize the translational success of stroke pharmacotherapeutic experiments.
|Alternate Journal||Int J Mol Sci|
|PubMed Central ID||PMC8836701|
|Grant List||R01 DA051812 / DA / NIDA NIH HHS / United States |
R01 NS084941 / NS / NINDS NIH HHS / United States
Blood-Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke.
Faculty Member Reference:
Thomas P Davis, PhD
Patrick T Ronaldson, PhD, FAAPS