Cells (Apr 2024)

The Temporal Relationship between Blood–Brain Barrier Integrity and Microglial Response following Neonatal Hypoxia Ischemia

  • Arya Jithoo,
  • Tayla R. Penny,
  • Yen Pham,
  • Amy E. Sutherland,
  • Madeleine J. Smith,
  • Maria Petraki,
  • Michael C. Fahey,
  • Graham Jenkin,
  • Atul Malhotra,
  • Suzanne L. Miller,
  • Courtney A. McDonald

DOI
https://doi.org/10.3390/cells13080660
Journal volume & issue
Vol. 13, no. 8
p. 660

Abstract

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Blood–brain barrier (BBB) dysfunction and neuroinflammation are key mechanisms of brain injury. We performed a time-course study following neonatal hypoxia–ischemia (HI) to characterize these events. HI brain injury was induced in postnatal day 10 rats by single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). At 6, 12, 24, and 72 h (h) post-HI, brains were collected to assess neuropathology and BBB dysfunction. A significant breakdown of the BBB was observed in the HI injury group compared to the sham group from 6 h in the cortex and hippocampus (p p p p < 0.0001), which significantly correlated to the peak of microbleeds. Neonatal HI insult leads to significant brain injury over the first 72 h that is mediated by BBB disruption within 6 h and a transitioning state of the resident microglia. Key BBB events coincide with the appearance of the intermediate microglial state and this relationship warrants further research and may be a key target for therapeutic intervention.

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