The brain's heart — Therapeutic opportunities for patent foramen ovale (PFO) and neurovascular disease

Ning, MingMing; Lo, Eng H.; Ning, Pei-Chen; Xu, Su Yu; McMullin, David; Demirjian, Zareh; Inglessis, Ignacio; Dec, GW; Palacios, Igor F.; Buonanno, Ferdinando S.

doi:10.1016/j.pharmthera.2013.03.007

Cited by 48 publications

(62 citation statements)

References 166 publications

(260 reference statements)

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“…That cerebral ischemia may result in cardiac myocyte death, complements a series of investigations that show the reverse interaction, whereby heart events lead to stroke-like brain pathology [15,[28][29][30]. A biological crosstalk involving the brain and the heart is corroborated by evidence demonstrating cardiac events result in a strokelike brain pathology.…”

Section: Introductionmentioning

confidence: 66%

Pathological links between stroke and cardiac arrest

et al. 2016

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There may be a pathological connection between cardiac failure and ischemic stroke. In this article we describe pertinent research that demonstrates subsequent death of cardiac and neural myocytes in the post ischemic stroke brain. Current stroke therapy overlooks the connection between cardiac and cerebrovascular events and fails to address the shared risk factors. Current pre-clinical stroke investigations have provided evidence that suggests the presence of an indirect cell death pathway in which toxic molecules emanate from the stroke brain and trigger cardiac cell death. On the other hand, other studies highlight the presence of a reverse cell death cascade in which toxic molecules from the heart, following cardiac arrest, travel to the brain and induce ischemic cell death. Further examination of these putative cell death pathways between ischemic stroke and cardiac arrest will prompt the advancement of innovative treatments specifically targeting both diseases, leading to ameliorated clinical results of patients diagnosed with heart failure and ischemic stroke.

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Section: Introductionmentioning

confidence: 66%

Pathological links between stroke and cardiac arrest

et al. 2016

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“…We observe that clinically, PFO-related stroke affects women of childbearing age, and that pregnancy, owing to major changes in hemocoagulative, hormonal, and cardiovascular parameters, can enhance stroke risks 1 2. However, the risks of PFO during pregnancy have not been systematically analyzed and their importance is not well understood.…”

Section: Introductionmentioning

confidence: 95%

Patent Foramen Ovale (Pfo), Stroke and Pregnancy

Chen

Deng

Palacios

et al. 2016

Journal of Investigative Medicine

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Patent foramen ovale (PFO)-related stroke is increasingly recognized as an important etiology of ischemic embolic stroke—accounting for up to 50% of strokes previously considered ‘cryptogenic’ or with an unknown mechanism. As a ‘back door to the brain,’ PFO can allow venous clots to enter arterial circulation via interatrial right-to-left shunting, potentially resulting in ischemic stroke. We observe that clinically, PFO-related stroke affects women of childbearing age, and that pregnancy—owing to major changes in hemocoagulative, hormonal, and cardiovascular parameters—can enhance stroke risks. However, no systematic study has been performed and little is known regarding complications, pregnancy outcomes and treatment for PFO-related stroke during pregnancy. To identify and characterize the complications and clinical outcomes related to PFOs during pregnancy, we performed a literature review and analysis from all reported cases of pregnancy with PFO-related complications in the medical literature from 1970 to 2015. We find that during pregnancy and postpartum, PFO is associated with complications affecting multiple organs, including the brain, heart and lung. The three principal complications reported are stroke, pulmonary emboli and myocardial infarction. In contrast to other pregnancy-related stroke etiologies, which peak during later pregnancy and postpartum, PFO-related stroke peaks during early pregnancy (first and second trimester—60%), and most patients had good neurological outcome (77%). In patients with PFO with recurrent stroke during pregnancy, additional key factors include high-risk PFO morphology (atrial septal aneurysm), larger right-to-left shunt, multiple gestation and concurrent hypercoagulability. Compared to strokes of other etiologies during pregnancy, most PFO stroke patients experienced uneventful delivery (93%) of healthy babies with a good clinical outcome. We conclude with recommended clinical treatment strategies for pregnant patients with PFO suggested by the data from these cases, and the clinical experience of our Cardio-Neurology Clinic.

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“…33 Cardiovascular disease may augment negative feedback loops among the brain, heart, and diseased vessels. 34,35 In the aged neurovascular niche, inflammatory microglia begin to suppress neurogenesis. 36 In aging white matter, oligodendrocyte precursors may lose their endogenous abilities for repair.…”

Section: Complex Mechanismsmentioning

confidence: 99%

2013 Thomas Willis Award Lecture

2014

Stroke

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Abstract-The pathophysiology of stroke is complex. Adaptive and maladaptive signalling occurs between multiple cell types in the brain. There is crosstalk between central and systemic responses. And there are overlapping pathways during initial injury and subsequent repair. These numerous feed-forward and feed-back interactions have made it difficult to translate experimental discoveries into clinical applications. An emerging hypothesis in biomedical research now suggests that contrary to a traditional model, translation may not be efficiently obtained without a rigorous understanding of mechanisms. Hence, to optimize diagnostics and therapeutics for stroke patients, it is necessary to identify and define causal mechanisms. Mirroring the multi-compartment interactions in stroke pathophysiology, bench-to-bedside, and bedside-back-to-bench advances in stroke may be best achieved with inter-disciplinary collaborations between basic research, neuroimaging, and broadly based clinical science. Causation can then be two-fold, ie, dissecting mechanisms and targets, as well as developing future scientists who can blur the boundaries between basic, translational, and clinical research. In systems theory, a critical goal is to distinguish causation from correlation. In stroke research, causation may perhaps be found through a collaborative search for mechanisms.

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The brain's heart — Therapeutic opportunities for patent foramen ovale (PFO) and neurovascular disease

Cited by 48 publications

References 166 publications

Pathological links between stroke and cardiac arrest

Pathological links between stroke and cardiac arrest

Patent Foramen Ovale (Pfo), Stroke and Pregnancy

2013 Thomas Willis Award Lecture

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