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Lai AY, Joo IL, Trivedi AU, et al. Cerebrovascular damage after midlife transient hypertension in non-transgenic and Alzheimer's disease rats. Brain Res. 2021;1758:147369doi: 10.1016/j.brainres.2021.147369.
Lai, A. Y., Joo, I. L., Trivedi, A. U., Dorr, A., Hill, M. E., Stefanovic, B., & McLaurin, J. (2021). Cerebrovascular damage after midlife transient hypertension in non-transgenic and Alzheimer's disease rats. Brain research, 1758147369. https://doi.org/10.1016/j.brainres.2021.147369
Lai, Aaron Y, et al. "Cerebrovascular damage after midlife transient hypertension in non-transgenic and Alzheimer's disease rats." Brain research vol. 1758 (2021): 147369. doi: https://doi.org/10.1016/j.brainres.2021.147369
Lai AY, Joo IL, Trivedi AU, Dorr A, Hill ME, Stefanovic B, McLaurin J. Cerebrovascular damage after midlife transient hypertension in non-transgenic and Alzheimer's disease rats. Brain Res. 2021 May 01;1758:147369. doi: 10.1016/j.brainres.2021.147369. Epub 2021 Feb 12. PMID: 33582120; PMCID: PMC8005286.
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Brain Res. 2021 May 01;1758:147369. doi: 10.1016/j.brainres.2021.147369. Epub 2021 Feb 12.

Cerebrovascular damage after midlife transient hypertension in non-transgenic and Alzheimer's disease rats.

Brain research

Aaron Y Lai, Illsung L Joo, Arunachala U Trivedi, Adrienne Dorr, Mary E Hill, Bojana Stefanovic, JoAnne McLaurin

Affiliations

  1. Biological Sciences, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. Electronic address: [email protected].
  2. Department of Medical Biophysics, University of Toronto, 1 King's College Circle, Toronto, Ontario M5G 2M9, Canada; Physical Sciences, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
  3. Biological Sciences, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. Electronic address: [email protected].
  4. Physical Sciences, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
  5. Biological Sciences, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. Electronic address: [email protected].
  6. Department of Medical Biophysics, University of Toronto, 1 King's College Circle, Toronto, Ontario M5G 2M9, Canada; Physical Sciences, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. Electronic address: [email protected].
  7. Biological Sciences, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5G 2M9, Canada. Electronic address: [email protected].

PMID: 33582120 PMCID: PMC8005286 DOI: 10.1016/j.brainres.2021.147369

Abstract

Hypertension, including transient events, is a major risk factor for developing late-onset dementia and Alzheimer's disease (AD). Anti-hypertensive drugs facilitate restoration of normotension without amelioration of increased dementia risk suggesting that transient hypertensive insults cause irreversible damage. This study characterized the contribution of transient hypertension to sustained brain damage as a function of normal aging and AD. To model transient hypertension, we treated F344TgAD and non-transgenic littermate rats with L-NG-Nitroarginine methyl ester (L-NAME) for one month, ceased treatment and allowed for a month of normotensive recovery. We then examined the changes in the structure and function of the cerebrovasculature, integrity of white matter, and progression of AD pathology. As independent factors, both transient hypertension and AD compromised structural and functional integrity across the vascular bed, while combined effects of hypertension and AD yielded the largest deficits. Combined effects of transient hypertension and AD genotype resulted in loss of cortical myelin particularly in the cingulate cortex which is crucial for cognitive function. Increased cerebral amyloid angiopathy, a prominent pathology of AD, was detected after transient hypertension as were up- and down-regulation of proteins associated with cerebrovascular remodeling - osteopontin, ROCK1 and ROCK2, in F344TgAD rats even 30 days after restoration of normotension. In conclusion, transient hypertension caused permanent cerebrovasculature and brain parenchymal damage in both normal aging and AD. Our results corroborate human studies that have found close correlation between transient hypertension in midlife and white matter lesions later in life outlining vascular pathologies as pathological links to increased risk of dementia.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Keywords: Alzheimer’s disease; Cerebral amyloid angiopathy; F344TgAD rat; Hypertension; Myelin; Vascular reactivity

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