The Effects of Hypoxia-Ischemia on the Neurovascular Unit in the Neonatal Brain

Riddick, Sydney Amber

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Year:: 2021
Contributor:: Riddick, Sydney Amber (creator); Stonestreet, M.D., Barbara (Advisor); Lim, M.D., Ph.D., Yow-Pin (Reader); Zimmerman, Ph.D., Anita (Reader); Brown University. Department of Molecular Pharmacology, Physiology and Biotechnology (sponsor)
Genre:: theses
Subject:: Blood-brain barrier; Newborn infants; Neurobiology; Astrocytes; Neuroscience; Hypoxic-ischemic encephalopathy; Brain--Blood-vessels; Membrane, Basement; Pericytes; Neurovascular unit
Extent:: 8, 31 p.

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Abstract:: The purpose of the current study was to examine the time-course of changes in vascular pericyte and astrocyte coverage and claudin-5 protein expression within the neurovascular unit (NVU), which results from exposure to a hypoxic-ischemic (HI) insult. These changes were examined in a widely used neonatal rat model to determine the outcomes of hypoxia-ischemia on the NVU and understand further the effects of hypoxia-ischemia on the neonatal brain and what the findings could mean for human newborns with HI insults. The current thesis focuses on the results of laminin/vessel density and vascular pericyte and astrocyte coverage. Brains were collected from rat pups exposed to right carotid artery ligation and hypoxia (HI) and recovery via reoxygenation at 6 hours (HI-6h: n=6) or 48 hours (HI-48h: n=5) after HI exposure or sham control treatment (Sham: n=6). All brains in the experimental groups experienced hypoxia. However, only the right side of each brain experienced ischemia, from reduced blood flow, because of ligation of the right carotid artery, which simulated a permanent hypoxia-ischemia model in the brain’s right hemisphere. Paraffin-embedded brain tissue was sectioned coronally and underwent immunohistochemical staining. On the left and right sides of the brain, images from the cerebral cortex, areas of white matter, and the hippocampus were randomly selected and obtained to study laminin density and vessel coverage. Two investigators independently examined the obtained images without knowledge of the experimental groups. In the right hemisphere, within the cerebral cortex, laminin density was higher than Sham at 6 and 48 hours after hypoxia-ischemia. Also, at 48 hours in the cerebral cortex, vessel density was higher in the hypoxia-ischemia exposed right hemisphere than in the hypoxia alone exposed left hemisphere. Vessel density was higher in white matter in the right hemisphere six hours after hypoxia-ischemia compared to Sham. In the cerebral cortex in the left hemisphere, vascular pericyte coverage was lower after 48 hours compared to Sham. In the cerebral cortex in the right hemisphere, after six hours, pericyte coverage was lower compared to Sham. No changes in vascular astrocyte coverage were observed in the brain regions examined at any time point following exposure to hypoxia or hypoxia-ischemia. The findings of the current study suggest that hypoxia-ischemia disrupts components of the NVU following HI exposure. Hypoxia-ischemia, as well as hypoxia alone, promotes vascular growth within 48 hours after exposure. With the cerebral cortex having a role in motor and cognitive functions and white matter mainly involved in motor functions, it will be imperative to find additional forms of treatment for newborns.
Notes:: Thesis (Sc. M.)--Brown University, 2021

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Citation

Riddick, Sydney Amber, "The Effects of Hypoxia-Ischemia on the Neurovascular Unit in the Neonatal Brain" (2021). Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:dgkpmfgw/

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Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations

Theses and Dissertations for the Molecular Pharmacology, Physiology, and Biotechnology department.
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