title: Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia-ischemia.
abstract: Insults to the developing brain often result in irreparable damage resulting in long-term deficits in motor and cognitive functions. The only treatment today for hypoxic-ischemic encephalopathy (HIE) in newborns is hypothermia, which has limited clinical benefit. We have studied changes to the blood-brain barriers (BBB) as well as regional cerebral blood flow (rCBF) in a neonatal model of HIE to further understand the underlying pathologic mechanisms. Nine-day old mice pups, brain roughly equivalent to the near-term human fetus, were subjected to hypoxia-ischemia. Hypoxia-ischemia increased BBB permeability to small and large molecules within hours after the insult, which normalized in the following days. The opening of the BBB was associated with changes to BBB protein expression whereas gene transcript levels were increased showing direct molecular damage to the BBB but also suggesting compensatory mechanisms. Brain pathology was closely related to reductions in rCBF during the hypoxia as well as the areas with compromised BBB showing that these are intimately linked. The transient opening of the BBB after the insult is likely to contribute to the pathology but at the same time provides an opportunity for therapeutics to better reach the infarcted areas in the brain.
authors: Department of Physiology, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: C Joakim
authors: CJ
authors: Ek
authors: Department of Physiology, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Barbara
authors: B
authors: D'Angelo
authors: 1] Department of Physiology, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden [2] Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, UK.
authors: Ana A
authors: AA
authors: Baburamani
authors: Spinal Cord Injury and Tissue Regeneration Center Salzburg, Department of Traumatology and Sport Injuries, Institute of Tendon and Bone Regeneration, Paracelsus Medical University, Salzburg, Austria; Austrian Cluster for Tissue Regeneration.
authors: Christine
authors: C
authors: Lehner
authors: Department of Physiology, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Anna-Lena
authors: AL
authors: Leverin
authors: Department of Physiology, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Peter L P
authors: PL
authors: Smith
authors: Department of Physiology, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Holger
authors: H
authors: Nilsson
authors: Department of Physiology, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Pernilla
authors: P
authors: Svedin
authors: 1] Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, UK [2] Departments of Obstetrics and Gynecology, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Henrik
authors: H
authors: Hagberg
authors: Department of Physiology, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Carina
authors: C
authors: Mallard
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000196:embryology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D005315:Fetal Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000196:embryology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice
references: Pediatr Res. 2005 Oct;58(4):791-8
references: 16189211
references: Stroke. 1988 Feb;19(2):245-50
references: 3344541
references: J Cereb Blood Flow Metab. 2000 Jan;20(1):10-4
references: 10616787
references: Pediatrics. 2002 Oct;110(4):673-80
references: 12359779
references: J Cereb Blood Flow Metab. 1996 Sep;16(5):1005-13
references: 8784246
references: J Neurosci. 2002 Jul 15;22(14):5910-9
references: 12122053
references: Brain Res. 1992 Sep 11;590(1-2):263-70
references: 1422834
references: Histochem Cell Biol. 2004 Jul;122(1):51-9
references: 15221411
references: Pharmacol Rev. 2005 Jun;57(2):173-85
references: 15914466
references: Ann N Y Acad Sci. 2009 May;1165:62-8
references: 19538289
references: BMJ. 2010;340:c363
references: 20144981
references: Pediatr Res. 1990 May;27(5):450-3
references: 2345670
references: Stroke. 1997 Nov;28(11):2281-8; discussion 2288-9
references: 9368577
references: Am J Physiol. 1978 Jan;234(1):H59-66
references: 623275
references: Ann Neurol. 2012 Apr;71(4):444-57
references: 22334391
references: Brain Res Dev Brain Res. 1991 Apr 24;59(2):231-5
references: 1914141
references: Exp Neurol. 2012 Jan;233(1):481-9
references: 22143064
references: Dev Neurosci. 2002;24(5):426-36
references: 12640182
references: J Cereb Blood Flow Metab. 1998 Feb;18(2):222-8
references: 9469166
references: Science. 2011 Dec 23;334(6063):1727-31
references: 22144466
references: J Cereb Blood Flow Metab. 2014 Apr;34(4):668-76
references: 24398931
references: J Neurosci. 2012 Jul 11;32(28):9588-600
references: 22787045
references: Exp Neurol. 2014 May;255:30-7
references: 24560715
references: J Biomed Biotechnol. 2010;2010:402593
references: 20224657
references: J Neurochem. 2004 Sep;90(5):1068-75
references: 15312162
references: J Comp Neurol. 2006 May 1;496(1):13-26
references: 16528724
references: J Cell Biol. 2003 May 12;161(3):653-60
references: 12743111
references: Am J Physiol. 1999 Feb;276(2 Pt 2):R283-9
references: 9950903
references: Nature. 2010 Nov 25;468(7323):562-6
references: 20944625
references: J Physiol. 2001 Nov 1;536(Pt 3):841-53
references: 11691876
references: Am J Obstet Gynecol. 2010 Jan;202(1):82.e1-9
references: 19889382
references: Histochem Cell Biol. 2012 Dec;138(6):861-79
references: 22886143
references: Pediatrics. 2008 Sep;122(3):e722-7
references: 18725389
references: J Cell Biol. 1998 Apr 20;141(2):397-408
references: 9548718
references: J Inherit Metab Dis. 2013 May;36(3):479-90
references: 23109062
references: Pediatr Neurol. 2004 Oct;31(4):254-7
references: 15464636
references: Trends Neurosci. 2008 Jun;31(6):279-86
references: 18471905
references: Front Physiol. 2012 Nov 09;3:424
references: 23162470
references: Biol Neonate. 2001;79(3-4):172-9
references: 11275647
references: J Pediatr. 2003 Nov;143(5):625-9
references: 14615734