Author:
Sayed Mohammed A.,Eldahshan Wael,Abdelbary Mahmoud,Pillai Bindu,Althomali Waleed,Johnson Maribeth H.,Arbab Ali S.,Ergul Adviye,Fagan Susan C.
Abstract
AbstractPost-stroke cognitive impairment (PSCI) is a major source of disability, affecting up to two thirds of stroke survivors with no available therapeutic options. The condition remains understudied in preclinical models due to its delayed presentation. Although hypertension is a leading risk factor for dementia, how ischemic stroke contributes to this neurodegenerative condition is unknown. In this study, we used a model of hypertension to study the development of PSCI and its mechanisms. Spontaneously hypertensive rats (SHR) were compared to normotensive rats and were subjected to 1-h middle cerebral artery occlusion or sham surgery. Novel object recognition, passive avoidance test and Morris water maze were used to assess cognition. In addition, brain magnetic resonance images were obtained 12-weeks post-stroke and tissue was collected for immunohistochemistry and protein quantification. Stroked animals developed impairment in long-term memory at 4-weeks post-stroke despite recovery from motor deficits, with hypertensive animals showing some symptoms of anhedonia. Stroked SHRs displayed grey matter atrophy and had a two-fold increase in apoptosis in the ischemic borderzone and increased markers of inflammatory cell death and DNA damage at 12 weeks post-stroke. This indicates that preexisting hypertension exacerbates the development of secondary neurodegeneration after stroke beyond its acute effects on neurovascular injury.
Funder
National Institutes of Health
U.S. Department of Veterans Affairs
Publisher
Springer Science and Business Media LLC
Reference61 articles.
1. Benjamin, E. J. et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation 137(12), e67–e492 (2018).
2. Towfighi, A. & Saver, J. L. Stroke declines from third to fourth leading cause of death in the United States: historical perspective and challenges ahead. Stroke 42(8), 2351–2355 (2011).
3. Sun, J. H., Tan, L. & Yu, J. T. Post-stroke cognitive impairment: epidemiology, mechanisms and management. Ann. Transl Med. 2(8), 80 (2014).
4. Woitzik, J., Back, T. & Thome, C. Flow-dependent versus spreading-like impairment of brain tissue integrity during focal cerebral ischemia and its consequences for neuroprotective strategies. Front. Biosci. 13, 1500–1506 (2008).
5. Leys, D. et al. Poststroke dementia. Lancet Neurol 4(11), 752–759 (2005).
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