Blood–brain barrier disruption in atrial fibrillation: a potential contributor to the increased risk of dementia and worsening of stroke outcomes?

Aryal, Ritambhara; Patabendige, Adjanie

doi:10.1098/rsob.200396

Cited by 15 publications

(16 citation statements)

References 258 publications

(332 reference statements)

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“…Many studies have detected a reduction in brain blood flow in patients and animal models of AF [249][250][251]. Aryal and Patabendige recently published a review that goes into detail explaining the mechanisms and methods of cerebral blood flow in AF and its relevance to stroke [252]. Although it appears likely that AF may disrupt the BBB, its mechanism of action needs further assessment.…”

Section: Atrial Fibrillationmentioning

confidence: 99%

Blood–Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke

Nilles

Williams

Betterton

et al. 2022

IJMS

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Globally, stroke is a leading cause of death and long-term disability. Over the past decades, several efforts have attempted to discover new drugs or repurpose existing therapeutics to promote post-stroke neurological recovery. Preclinical stroke studies have reported successes in identifying novel neuroprotective agents; however, none of these compounds have advanced beyond a phase III clinical trial. One reason for these failures is the lack of consideration of blood–brain barrier (BBB) transport mechanisms that can enable these drugs to achieve efficacious concentrations in ischemic brain tissue. Despite the knowledge that drugs with neuroprotective properties (i.e., statins, memantine, metformin) are substrates for endogenous BBB transporters, preclinical stroke research has not extensively studied the role of transporters in central nervous system (CNS) drug delivery. Here, we review current knowledge on specific BBB uptake transporters (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents); organic cation transporters (OCTs in humans; Octs in rodents) that can be targeted for improved neuroprotective drug delivery. Additionally, we provide state-of-the-art perspectives on how transporter pharmacology can be integrated into preclinical stroke research. Specifically, we discuss the utility of in vivo stroke models to transporter studies and considerations (i.e., species selection, co-morbid conditions) that will optimize the translational success of stroke pharmacotherapeutic experiments.

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Section: Atrial Fibrillationmentioning

confidence: 99%

Blood–Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke

Nilles

Williams

Betterton

et al. 2022

IJMS

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“…BBB disruption might represent a first step preceding structural brain damage in the context of cardiac disease. BBB disruption was observed for AF 48 and appears also plausible for other cardiac conditions associated with altered CBF, such as HF. The neurovascular unit represents an essential functional compartment of the brain, composed of vascular cells, glial cells, and neurons.…”

Section: Narrativementioning

confidence: 76%

Section: 49mentioning

confidence: 78%

Circulating cardiac biomarkers, structural brain changes, and dementia: Emerging insights and perspectives

Jensen

Zeller

Twerenbold

et al. 2023

Alzheimer's & Dementia

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Diseases of the heart and brain are strongly linked to each other, and cardiac dysfunction is associated with cognitive decline and dementia. This link between cardiovascular disease and dementia offers opportunities for dementia prevention through prevention and treatment of cardiovascular risk factors and heart disease. Increasing evidence suggests the clinical utility of cardiac biomarkers as risk markers for structural brain changes and cognitive impairment. We propose the hypothesis that structural brain changes are the link between impaired cardiac function, as captured by blood-based cardiac biomarkers, and cognitive impairment. This review provides an overview of the literature and illustrates emerging insights into the association of markers of hemodynamic stress (natriuretic peptides) and markers of myocardial injury (cardiac troponins) with imaging findings of brain damage and cognitive impairment or dementia. Based on these findings, we discuss potential pathophysiological mechanisms underlying the association of cardiac biomarkers with structural brain changes and dementia. We suggest testable hypotheses and a research plan to close the gaps in understanding the mechanisms linking vascular damage and neurodegeneration, and to pave the way for targeted effective interventions for dementia prevention. From a clinical perspective, cardiac biomarkers open the window for early identification of patients at risk of dementia, who represent a target population for preventive interventions targeting modifiable cardiovascular risk factors to avert cognitive decline and dementia.

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“…So that the brain can function despite the presence of a BBB, essential molecules or proteins cross the BBB and enter the cerebrospinal fluid (CSF) via an array of molecular transporters (eg, efflux and solute carriers) and receptors. [246][247][248][249] BBB function is facilitated by support cells, particularly perivascular astrocytes and capillary pericytes. 247 In relation to disease, a progressive decline in BBB function occurs normally with aging, 247 a change that can be accelerated by the presence of hypertension.…”

Section: Blood-brain Barriermentioning

confidence: 99%

Hypertension: Causes and Consequences of Circadian Rhythms in Blood Pressure

Faraci,

Scheer

2024

Circulation Research

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Hypertension is extremely common, affecting approximately 1 in every 2 adults globally. Chronic hypertension is the leading modifiable risk factor for cardiovascular disease and premature mortality worldwide. Despite considerable efforts to define mechanisms that underlie hypertension, a potentially major component of the disease, the role of circadian biology has been relatively overlooked in both preclinical models and humans. Although the presence of daily and circadian patterns has been observed from the level of the genome to the whole organism, the functional and structural impact of biological rhythms, including mechanisms such as circadian misalignment, remains relatively poorly defined. Here, we review the impact of daily rhythms and circadian systems in regulating blood pressure and the onset, progression, and consequences of hypertension. There is an emphasis on the impact of circadian biology in relation to vascular disease and end-organ effects that, individually or in combination, contribute to complex phenotypes such as cognitive decline and the loss of cardiac and brain health. Despite effective treatment options for some individuals, control of blood pressure remains inadequate in a substantial portion of the hypertensive population. Greater insight into circadian biology may form a foundation for novel and more widely effective molecular therapies or interventions to help in the prevention, treatment, and management of hypertension and its related pathophysiology.

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Blood–brain barrier disruption in atrial fibrillation: a potential contributor to the increased risk of dementia and worsening of stroke outcomes?

Cited by 15 publications

References 258 publications

Blood–Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke

Blood–Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke

Circulating cardiac biomarkers, structural brain changes, and dementia: Emerging insights and perspectives

Hypertension: Causes and Consequences of Circadian Rhythms in Blood Pressure

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