Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia-ischemia

C. Joakim Ek*, Barbara D'Angelo, Ana A. Baburamani, Christine Lehner, Anna Lena Leverin, Peter L P Smith, Holger Nilsson, Pernilla Svedin, Henrik Hagberg, Carina Mallard

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)818-827
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume35
Issue number5
Early online date28 Jan 2015
DOIs
Publication statusPublished - May 2015

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