"Blood Brain Barrier Alterations Induced By Hypoxia / Stroke - Challenges to Drug Delivery for Stroke". Stroke affects a million people every year in the U.S. alone and costs billions of dollars in medical treatment and lost productivity. To date many of the investigations concerning the blood brain barrier (BBB) and the delivery of therapeutics to the CNS to treat stroke pathologies have been performed in naive animals or preclinical models of stroke. It is clear that the BBB is not a static barrier, and is not open at all times in stroke , but can be modulated and challenged by a number of factors from the immune, neuronal , glial , endothelial and hormonal systems. During hypoxia or stroke each of the neurovascular unit (NVU) cell types are activated and altered in a unique manner. We are currently investigating specific NVU cell types, BBB tight junction (TJ) proteins Claudin 5 and Occludin , P-gp and OATP 1a4 transporter function, trafficking , and drug - drug interaction with Acetaminophen in both acute pain and rodent models of stroke. The BBB preclinical models (MCAO) we study for stroke do not merely "leak" as defined by "opening of the barrier" in all brain regions. We have discovered that stroke and hypoxia pathologies modify the delivery of therapeutic drugs, such as statin neuroprotectants, and pain relieving opioids, via specific transporters at the BBB that can be targeted. Our most recent report is that the stroke neuroprotectant atorvistatin requires delivery to the CNS by the BBB transporter OATP 1a4 and provides evidence that one can not always rely on an "open" or "closed" BBB alone for drug delivery treatment in stroke, as BBB transporters play a critical role in drug delivery as well.
