title: Blood brain barrier is impermeable to solutes and permeable to water after experimental pediatric cardiac arrest.
abstract: Pediatric asphyxial cardiac arrest (CA) results in unfavorable neurological outcome in most survivors. Development of neuroprotective therapies is contingent upon understanding the permeability of intravenously delivered medications through the blood brain barrier (BBB). In a model of pediatric CA we sought to characterize BBB permeability to small and large molecular weight substances. Additionally, we measured the percent brain water after CA. Asphyxia of 9 min was induced in 16-18 day-old rats. The rats were resuscitated and the BBB permeability to small (sodium fluorescein and gadoteridol) and large (immunoglobulin G, IgG) molecules was assessed at 1, 4, and 24 h after asphyxial CA or sham surgery. Percent brain water was measured post-CA and in shams using wet-to-dry brain weight. Fluorescence, gadoteridol uptake, or IgG staining at 1, 4h and over the entire 24 h post-CA did not differ from shams, suggesting absence of BBB permeability to these solutes. Cerebral water content was increased at 3h post-CA vs. sham. In conclusion, after 9 min of asphyxial CA there is no BBB permeability over 24h to conventional small or large molecule tracers despite the fact that cerebral water content is increased early post-CA indicating the development of brain edema. Evaluation of novel therapies targeting neuronal death after pediatric CA should include their capacity to cross the BBB.
authors.affiliation: University of Pittsburgh, Department of Pediatrics, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Electronic address: Erika.Tress@UHhospitals.org.
authors.forename: Erika E
authors.initials: EE
authors.lastname: Tress
authors.affiliation: University of Pittsburgh, Department of Pediatrics, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; University of Pittsburgh, Critical Care Medicine, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA; University of Pittsburgh, Safar Center for Resuscitation Research, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA. Electronic address: clarkrs@ccm.upmc.edu.
authors.forename: Robert S B
authors.initials: RS
authors.lastname: Clark
authors.affiliation: Carnegie Mellon University, NMR Center for Biomedical Research, 4400 Fifth Avenue, Pittsburgh, PA 15213, USA. Electronic address: lmfoley@andrew.cmu.edu.
authors.forename: Lesley M
authors.initials: LM
authors.lastname: Foley
authors.affiliation: University of Pittsburgh, Critical Care Medicine, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA; University of Pittsburgh, Safar Center for Resuscitation Research, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA. Electronic address: AlexanderHL@anes.upmc.edu.
authors.forename: Henry
authors.initials: H
authors.lastname: Alexander
authors.affiliation: University of Pittsburgh, Department of Pediatrics, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Electronic address: Robert.Hickey@chp.edu.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Hickey
authors.affiliation: University of Pittsburgh, Safar Center for Resuscitation Research, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA; University of Pittsburgh Department of Anesthesiology, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA. Electronic address: drabtx@upmc.edu.
authors.forename: Tomas
authors.initials: T
authors.lastname: Drabek
authors.affiliation: University of Pittsburgh, Department of Pediatrics, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; University of Pittsburgh, Critical Care Medicine, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA; University of Pittsburgh, Safar Center for Resuscitation Research, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA. Electronic address: kochanekpm@ccm.upmc.edu.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.affiliation: University of Pittsburgh, Department of Pediatrics, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; University of Pittsburgh, Safar Center for Resuscitation Research, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA. Electronic address: mioara.manole@chp.edu.
authors.forename: Mioara D
authors.initials: MD
authors.lastname: Manole
mesh_terms: D000367:Age Factors; D000818:Animals; D001237:Asphyxia / Q000150:complications / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D019793:Fluorescein / Q000378:metabolism / Q000493:pharmacokinetics; D005682:Gadolinium / Q000378:metabolism / Q000493:pharmacokinetics; D006323:Heart Arrest / Q000209:etiology / Q000378:metabolism*; D006571:Heterocyclic Compounds / Q000378:metabolism / Q000493:pharmacokinetics; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D009942:Organometallic Compounds / Q000378:metabolism / Q000493:pharmacokinetics; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000378:metabolism*
chemical_list: D006571:Heterocyclic Compounds; D007074:Immunoglobulin G; D009942:Organometallic Compounds; C062402:gadoteridol; D014867:Water; D005682:Gadolinium; D019793:Fluorescein
keywords: Asphyxia; Blood brain barrier; Cardiac arrest; Permeability; Rat