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Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice
Published on: May 4, 2015
Vascular response to hypoxic preconditioning in the immature brain
Malin Gustavsson1, Carina Mallard, Susan J Vannucci
1Perinatal Center, Department of Physiology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Summary
Hypoxic preconditioning protects the immature brain by increasing vascular density and upregulating protective genes, significantly attenuating cerebral blood flow reduction during subsequent hypoxic-ischemic injury.
Area of Science:
- Neuroscience
- Vascular Biology
- Neonatal Physiology
Background:
- The immature brain is vulnerable to hypoxic-ischemic (HI) injury.
- Microvascular modifications may influence brain response to HI.
- Hypoxic preconditioning (PC) is a potential protective strategy.
Purpose of the Study:
- To investigate if hypoxic preconditioning modifies immature brain microvasculature and affects cerebral blood flow (CBF) during subsequent HI.
- To identify molecular changes associated with PC.
Main Methods:
- Rats were exposed to hypoxia or normoxia on postnatal day 6 for hypoxic preconditioning.
- Unilateral HI was induced 24 hours later.
- CBF was measured using 14C-iodoantipyrine and laser Doppler flowmetry.
- Gene expression and vascular density were analyzed.
Main Results:
- Hypoxic preconditioning significantly attenuated the decrease in CBF during HI.
- Vascular gene expression was altered, with several genes upregulated post-PC.
- Vascular density increased significantly after hypoxic preconditioning.
Conclusions:
- Hypoxic preconditioning enhances tolerance to HI injury in the immature brain.
- Increased vascular density and altered vascular gene expression contribute to neuroprotection.
- Nitric oxide synthase inhibition did not alter CBF during HI after PC.
