Characterizing the molecular signaling pathways in the cerebral arteries of stroke-prone spontaneously hypertensive rate (SHRsp) before and after stroke

Chokshi, Killol (2018) Characterizing the molecular signaling pathways in the cerebral arteries of stroke-prone spontaneously hypertensive rate (SHRsp) before and after stroke. Masters thesis, Memorial University of Newfoundland.

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Background: Hemorrhagic stroke (HS) is associated with loss of middle cerebral artery (MCA) autoregulation in the stroke-prone spontaneously hypertensive rat (SHRsp). We believe the MCA dysfunction may be due to increased inflammatory signalling (p38MAPK and ERK) and decreased contractile signalling (MLC and PKC) in the MCA during stroke, altered calcium (TRPV4) channel expression, accompanied with increased neuro-inflammation (astrocyte and microglia) and neuronal damage in brain after stroke. Methods: SHRsps were fed a high salt (4%NaCl) diet and sacrificed at nine weeks of age for pre-stroke and after evidence of stroke (~15 weeks) for post-stroke samples. The MCAs were isolated to measure protein levels and expression using immunofluorescence (IF), and western blot (WB) for inflammatory and contractile proteins. Tissues were analyzed for activation of neuro-inflammation, neuronal damage, for total and activated inflammatory proteins (ERK1/2 and p38MAPK), cerebrovascular contraction (PKC and MLC), and changes involved in transient receptor potential V4 (TRPV4) activation. Results: Results from both WB and IF indicate an increase in activated inflammatory proteins post-stroke, with an associated decrease in expression of activated contractile proteins and TRPV4 channel compared to pre-stroke SHRsp. The post-stroke samples also show significant increase in neuro-inflammation and neuronal damage compared to pre-stroke samples. Conclusion: The results show an increase in ratio of activated/total (p38 MAPK and ERK1/2) accompanied with a decrease in activated/total PKC and TRPV4 channel expression in post-stroke which may relate to a decrease in vessel structural integrity and alter vascular tone in the MCAs effecting its ability to contract in response to pressure. Significant neuro-inflammation and neuronal damage in the brain tissue surrounding the MCA in post-stroke samples confirm MCA dysfunction accompanies brain damage during stroke.

Item Type: Thesis (Masters)
Item ID: 13717
Additional Information: Includes bibliographical references (pages 100-117).
Keywords: Hemorrhagic stroke, Middle cerebral artery, Stroke-prone spontaneously hypertensive rats (SHRsp), cerebrovascular dysfunction, hemorrhagic stroke pathology, signalling changes in hemorrhagic stroke, High blood pressure
Department(s): Pharmacy, School of
Date: October 2018
Date Type: Submission
Library of Congress Subject Heading: Cerebrovascular disease--Pathophysiology; Brain--Hemorrhage--Pathophysiology

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