Blood brain barrier is impermeable to solutes and permeable to water after experimental pediatric cardiac arrest

• Published in: Neuroscience letters 2014-08, Vol.578, p.17-21
• Main Authors: Tress, Erika E., Clark, Robert S.B., Foley, Lesley M., Alexander, Henry, Hickey, Robert W., Drabek, Tomas, Kochanek, Patrick M., Manole, Mioara D.
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Asphyxia; Asphyxia - complications; Asphyxia - metabolism; Blood brain barrier; Blood-Brain Barrier - metabolism; Body Water - metabolism; Brain - metabolism; Cardiac arrest; Disease Models, Animal; Female; Fluorescein - metabolism; Fluorescein - pharmacokinetics; Gadolinium - metabolism; Gadolinium - pharmacokinetics; Heart Arrest - etiology; Heart Arrest - metabolism; Heterocyclic Compounds - metabolism; Heterocyclic Compounds - pharmacokinetics; Immunoglobulin G - metabolism; Male; Organometallic Compounds - metabolism; Organometallic Compounds - pharmacokinetics; Permeability; Rat; Rats; Rats, Sprague-Dawley; Water - metabolism
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2014.06.020

•We assessed blood brain barrier permeability in a pediatric model of cardiac arrest.•We evaluated the percent brain water in a pediatric model of cardiac arrest.•Blood brain barrier was impermeable to small or large molecular weight substances.•Cerebral water content was increased at 3h post-resuscitation.•Evaluation of neuroprotective therapies in pediatric CA should include their ability to cross BBB. 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 9min 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 24h 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 24h 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 9min 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.