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Blood-brain barrier permeability following intracerebral hemorrhage is related to local ion dyshomeostasis Open Access


Other title
Blood-brain barrier
Intracerebral hemorrhage
Ion dyshomeostasis
Type of item
Degree grantor
University of Alberta
Author or creator
Nadeau, Colby A
Supervisor and department
Colbourne, Frederick (Psychology)
Examining committee member and department
Winship, Ian (Psychiatry)
Fouad, Karim (Physical Therapy)
Mathewson, Kyle (Psychology)
Department of Psychology

Date accepted
Graduation date
2017-11:Fall 2017
Master of Science
Degree level
Background: Increased blood-brain barrier (BBB) permeability is seen after intracerebral hemorrhage (ICH). Following ICH, BBB dysfunction occurs due to direct (e.g. mechanical damage) and indirect (e.g. inflammation) injury. Damage to the BBB prevents maintenance of brain homeostasis. This thesis seeks to elucidate the time course of BBB permeability after ICH and investigate its relationship to local ion dyshomeostasis using novel imaging techniques. Methods: Bacterial collagenase was used to cause a striatal hemorrhage in rats. In experiment 1, animals were euthanized at days 3, 7, and 14 post-ICH following injection of Evans Blue dye to measure BBB permeability. In experiment 2, animals were euthanized at day 3 post-ICH after injection with a gadolinium-based contrast agent. A novel in situ biospectroscopic imaging technique was used to spatially assess changes in iron, chlorine, potassium, manganese, zinc, calcium, and copper in relation to BBB permeability. Results: After stroke, BBB permeability was significantly elevated at day 3 and decreased over time (time main effect; P < 0.001). At day 3 and day 7, BBB permeability was significantly elevated in the IPSI hemisphere as compared to SHAM samples (P < 0.001; P < 0.05, respectively). Contralateral BBB permeability did not differ between experimental groups at any survival time (P > 0.05). A subset of animals displayed BBB hyperpermeability (i.e. greater than maximum SHAM levels) at all times sampled. Chloride, iron, potassium, and manganese dyshomeostasis occurred in the hematoma (P < 0.001). Chloride, iron, and potassium levels normalized with distance into the perihematoma zone (distance main effect; P < 0.001, P < 0.001, P < 0.001, respectively). Elevated gadolinium levels were found in the hematoma (P < 0.05) and the perihematoma zone (distance main effect; P < 0.001). There was a relationship between gadolinium levels and ion dyshomeostasis in the perihematoma, but not hematoma, zone. Conclusions: After experimental ICH, BBB permeability is elevated acutely, and BBB dysfunction may persist for two weeks. A subset of animals display hyperpermeability at days 3, 7, and 14 after ICH. This elevated permeability may indicate the presence of cerebral microbleeds or angiogenesis. Furthermore, ion dyshomeostasis and BBB dysfunction occur in the perihematoma zone three days after ICH. Future work should directly assess the contribution of BBB disruption to ion dyshomeostasis and its impact on functional outcome.
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