title: Tools for studying drug transport and metabolism in the brain.
abstract: BACKGROUND
  Development of xenobiotics that cross the blood-brain barrier in therapeutically-relevant quantities is an expensive and time-consuming undertaking. However, central nervous system diseases are an under-addressed cause of high mortality and morbidity, and drug development in this field is a worthwhile venture.
  
  
  METHODS
  We aim to familiarize the reader with available methodologies for studying drug transport into the brain. Current understanding of the blood-brain barrier structure has been well-described in other manuscripts, and first we briefly review the path that xenobiotics take through the brain - from bloodstream, to endothelial cells of the blood-brain barrier, to interstitial space, to brain parenchymal cells, and then to an exit point from the central nervous system. The second half of the review discusses research tools available to determine if xenobiotics are making the journey through the brain successfully and offers commentary on the translational utility of each methodology.
  
  
  CONCLUSIONS
  Theoretically, non-human mammalian and human blood-brain barriers are similar in composition; however, some findings demonstrate important differences across species. Translational methodologies may provide more reliable information about how a drug may act across species. The recent finding of lymphatic vessels within the central nervous system may provide new tools and strategies for drug delivery to the brain.
authors.affiliation: a Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School , The University of Texas Health Science Center at Houston , Houston , TX , USA.
authors.forename: Meagan R
authors.initials: MR
authors.lastname: Pitcher
authors.affiliation: a Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School , The University of Texas Health Science Center at Houston , Houston , TX , USA.|b Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School , The University of Texas Health Science Center at Houston , Houston , TX , USA.|c Neuroscience Graduate Program, Graduate School of Biomedical Sciences , The University of Texas Health Science Center at Houston , Houston , TX , USA.|d Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit , University of Southern Santa Catarina , Criciúma , Santa Catarina , Brazil.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism; D013045:Species Specificity; D057170:Translational Research, Biomedical / Q000379:methods; D015262:Xenobiotics / Q000493:pharmacokinetics*
chemical_list: D004364:Pharmaceutical Preparations; D015262:Xenobiotics
keywords: Blood-brain barrier; cerebrospinal fluid; drug transport; microdialysis; neuroimaging