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Unpuzzling the Comorbid Type 2 Diabetes and Hypertension-Related Cognitive Dysfunction and Stroke

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Neuroprotective Therapy for Stroke and Ischemic Disease

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Type 2 diabetes (T2D) is a highly disabling, major socioeconomic burden, whose long-term complications (particularly those affecting the central nervous system (CNS), as Alzheimer disease (AD)) can be further exacerbated by the frequent development of comorbid hypertension. Although the precise mechanisms involved herein remain elusive, it is conceivable that chronic T2D-related brain insulin resistance (IRES) and hyperglycemia may crosstalk with an overactivated brain renin-angiotensin-II-aldosterone system (RAAS) further potentiating the hypertension-related injury and culminating in cognitive dysfunction and AD. Indeed, several studies showed the contribution of abnormal RAAS activation upon hypertension per se to the pathophysiology of CNS disorders, such as stroke and AD. However, most of this available knowledge relies on the indirect effects of pharmacological inhibition of RAAS by drugs belonging either to the angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors (ACEi) groups. For instance, antihypertensive drugs have also shown anti-neuroinflammatory properties, widely known to play a pivotal role in brain and cognitive dysfunction.

In sum, albeit during the last two decades a bulk of scientific knowledge has progressively unravelled the molecular mechanisms that lead to chronic T2D-related CNS injury, the information available regarding its exacerbation upon the quite frequent comorbid hypertension is still scarce and somehow controversial. In this perspective, we aim to briefly review some of the subcellular mechanisms (e.g., oxidative stress) that may underlie the hypertension-induced (per se or as a comorbidity to T2D) brain and cognitive dysfunction, vascular dementia (particularly AD), and stroke. We will also briefly discuss the pharmacological evidence on the neuroprotection afforded by antihypertensive drugs.

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Acknowledgements

This work was supported by European funds from FEDER, through the Programa Operacional Factores de Competitividade—COMPETE 2020; by Portuguese funds from FCT—Fundação para a Ciência e a Tecnologia (Strategic Project: UID/NEU/04539/2013); and by European Social Fund: Fellowships SFRH/BPD/84473/2012 to A. I. Duarte and SFRH/BD/90036/2012 to E. Candeias.

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Authors and Affiliations

  1. CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, Faculty of Medicine (Pólo 1, 1st Floor), 3004-517, Coimbra, Portugal

    I. Sebastião, E. Candeias, M. S. Santos, C. R. Oliveira, Paula I. Moreira & Ana I. Duarte

  2. Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Casa Costa Alemão—Pólo II, Rua D. Francisco de Lemos, 3030-789, Coimbra, Portugal

    E. Candeias & Ana I. Duarte

  3. Life Sciences Department, University of Coimbra, Largo Marquês de Pombal, 3004-517, Coimbra, Portugal

    M. S. Santos

  4. Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504, Coimbra, Portugal

    C. R. Oliveira

  5. Institute of Physiology, Faculty of Medicine, University of Coimbra, 3004-504, Coimbra, Portugal

    Paula I. Moreira

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  1. I. Sebastião
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  2. E. Candeias
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  3. M. S. Santos
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  4. C. R. Oliveira
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  5. Paula I. Moreira
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  6. Ana I. Duarte
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Correspondence to Paula I. Moreira or Ana I. Duarte .

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  1. Department of Neurology and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA

    Paul A. Lapchak

  2. Loma Linda University School of Medicine, Loma Linda, California, USA

    John H. Zhang

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Sebastião, I., Candeias, E., Santos, M.S., Oliveira, C.R., Moreira, P.I., Duarte, A.I. (2017). Unpuzzling the Comorbid Type 2 Diabetes and Hypertension-Related Cognitive Dysfunction and Stroke. In: Lapchak, P., Zhang, J. (eds) Neuroprotective Therapy for Stroke and Ischemic Disease. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-45345-3_31

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