Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats

Introduction: Spontaneously hypertensive stroke-prone rats (SHRSP) are used to model clinically relevant aspects of human cerebral small vessel disease (CSVD). To decipher and understand the underlying disease dynamics, assessment of the temporal progression of CSVD histopathological and neuroimagin...

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Autores principales:	Yousef Hannawi, Eder Caceres, Mohamed G. Ewees, Kimerly A. Powell, Anna Bratasz, Jan M. Schwab, Cameron L. Rink, Jay L. Zweier
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	cerebral small vessel disease magnetic resonance imaging sensorimotor testing spontaneously hypertensive stroke prone rat Wistar Kyoto Rat Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/c75e0ce9ae514406b9dc62b33ea64d93
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spelling	oai:doaj.org-article:c75e0ce9ae514406b9dc62b33ea64d932021-12-01T18:45:48ZCharacterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats1664-229510.3389/fneur.2021.740298https://doaj.org/article/c75e0ce9ae514406b9dc62b33ea64d932021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fneur.2021.740298/fullhttps://doaj.org/toc/1664-2295Introduction: Spontaneously hypertensive stroke-prone rats (SHRSP) are used to model clinically relevant aspects of human cerebral small vessel disease (CSVD). To decipher and understand the underlying disease dynamics, assessment of the temporal progression of CSVD histopathological and neuroimaging correlates is essential.Materials and Methods: Eighty age-matched male SHRSP and control Wistar Kyoto rats (WKY) were randomly divided into four groups that were aged until 7, 16, 24 and 32 weeks. Sensorimotor testing was performed weekly. Brain MRI was acquired at each study time point followed by histological analyses of the brain.Results: Compared to WKY controls, the SHRSP showed significantly higher prevalence of small subcortical hyperintensities on T2w imaging that progressed in size and frequency with aging. Volumetric analysis revealed smaller intracranial and white matter volumes on brain MRI in SHRSP compared to age-matched WKY. Diffusion tensor imaging (DTI) showed significantly higher mean diffusivity in the corpus callosum and external capsule in WKY compared to SHRSP. The SHRSP displayed signs of motor restlessness compared to WKY represented by hyperactivity in sensorimotor testing at the beginning of the experiment which decreased with age. Distinct pathological hallmarks of CSVD, such as enlarged perivascular spaces, microbleeds/red blood cell extravasation, hemosiderin deposits, and lipohyalinosis/vascular wall thickening progressively accumulated with age in SHRSP.Conclusions: Four stages of CSVD severity in SHRSP are described at the study time points. In addition, we find that quantitative analyses of brain MRI enable identification of in vivo markers of CSVD that can serve as endpoints for interventional testing in therapeutic studies.Yousef HannawiEder CaceresMohamed G. EweesMohamed G. EweesKimerly A. PowellKimerly A. PowellAnna BrataszJan M. SchwabJan M. SchwabJan M. SchwabJan M. SchwabCameron L. RinkJay L. ZweierFrontiers Media S.A.articlecerebral small vessel diseasemagnetic resonance imagingsensorimotor testingspontaneously hypertensive stroke prone ratWistar Kyoto RatNeurology. Diseases of the nervous systemRC346-429ENFrontiers in Neurology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cerebral small vessel disease magnetic resonance imaging sensorimotor testing spontaneously hypertensive stroke prone rat Wistar Kyoto Rat Neurology. Diseases of the nervous system RC346-429
spellingShingle	cerebral small vessel disease magnetic resonance imaging sensorimotor testing spontaneously hypertensive stroke prone rat Wistar Kyoto Rat Neurology. Diseases of the nervous system RC346-429 Yousef Hannawi Eder Caceres Mohamed G. Ewees Mohamed G. Ewees Kimerly A. Powell Kimerly A. Powell Anna Bratasz Jan M. Schwab Jan M. Schwab Jan M. Schwab Jan M. Schwab Cameron L. Rink Jay L. Zweier Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats
description	Introduction: Spontaneously hypertensive stroke-prone rats (SHRSP) are used to model clinically relevant aspects of human cerebral small vessel disease (CSVD). To decipher and understand the underlying disease dynamics, assessment of the temporal progression of CSVD histopathological and neuroimaging correlates is essential.Materials and Methods: Eighty age-matched male SHRSP and control Wistar Kyoto rats (WKY) were randomly divided into four groups that were aged until 7, 16, 24 and 32 weeks. Sensorimotor testing was performed weekly. Brain MRI was acquired at each study time point followed by histological analyses of the brain.Results: Compared to WKY controls, the SHRSP showed significantly higher prevalence of small subcortical hyperintensities on T2w imaging that progressed in size and frequency with aging. Volumetric analysis revealed smaller intracranial and white matter volumes on brain MRI in SHRSP compared to age-matched WKY. Diffusion tensor imaging (DTI) showed significantly higher mean diffusivity in the corpus callosum and external capsule in WKY compared to SHRSP. The SHRSP displayed signs of motor restlessness compared to WKY represented by hyperactivity in sensorimotor testing at the beginning of the experiment which decreased with age. Distinct pathological hallmarks of CSVD, such as enlarged perivascular spaces, microbleeds/red blood cell extravasation, hemosiderin deposits, and lipohyalinosis/vascular wall thickening progressively accumulated with age in SHRSP.Conclusions: Four stages of CSVD severity in SHRSP are described at the study time points. In addition, we find that quantitative analyses of brain MRI enable identification of in vivo markers of CSVD that can serve as endpoints for interventional testing in therapeutic studies.
format	article
author	Yousef Hannawi Eder Caceres Mohamed G. Ewees Mohamed G. Ewees Kimerly A. Powell Kimerly A. Powell Anna Bratasz Jan M. Schwab Jan M. Schwab Jan M. Schwab Jan M. Schwab Cameron L. Rink Jay L. Zweier
author_facet	Yousef Hannawi Eder Caceres Mohamed G. Ewees Mohamed G. Ewees Kimerly A. Powell Kimerly A. Powell Anna Bratasz Jan M. Schwab Jan M. Schwab Jan M. Schwab Jan M. Schwab Cameron L. Rink Jay L. Zweier
author_sort	Yousef Hannawi
title	Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats
title_short	Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats
title_full	Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats
title_fullStr	Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats
title_full_unstemmed	Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats
title_sort	characterizing the neuroimaging and histopathological correlates of cerebral small vessel disease in spontaneously hypertensive stroke-prone rats
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c75e0ce9ae514406b9dc62b33ea64d93
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Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats

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