Dataset Information

Cerebrovascular dysfunction with stress and depression.

ABSTRACT: Maintenance of adequate tissue perfusion through a dense network of cerebral microvessels is critical for the perseveration of normal brain function. Regulation of the cerebral blood flow has to ensure adequate delivery of nutrients and oxygen with moment-to-moment adjustments to avoid both hypo- and hyper-perfusion of the brain tissue. Even mild impairments of cerebral blood flow regulation can have significant implications on brain function. Evidence suggests that chronic stress and depression elicits multifaceted functional impairments to the cerebral microcirculation, which plays a critical role in brain health and the pathogenesis of stress-related cognitive impairment and cerebrovascular events. Identifying the functional and structural changes to the brain that are induced by stress is crucial for achieving a realistic understanding of how related illnesses, which are highly disabling and with a large economic cost, can be managed or reversed. This overview discusses the stress-induced alterations in neurovascular coupling with specific attention to cerebrovascular regulation (endothelial dependent and independent vasomotor function, microvessel density). The pathophysiological consequences of cerebral microvascular dysfunction with stress and depression are explored.

SUBMITTER: Burrage E

PROVIDER: S-EPMC6126243 | biostudies-other | 2018 Apr-Jun

REPOSITORIES: biostudies-other

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Cerebrovascular dysfunction with stress and depression.

Burrage Emily E Marshall Kent L KL Santanam Nalini N Chantler Paul D PD

Brain circulation 20180401 2

Maintenance of adequate tissue perfusion through a dense network of cerebral microvessels is critical for the perseveration of normal brain function. Regulation of the cerebral blood flow has to ensure adequate delivery of nutrients and oxygen with moment-to-moment adjustments to avoid both hypo- and hyper-perfusion of the brain tissue. Even mild impairments of cerebral blood flow regulation can have significant implications on brain function. Evidence suggests that chronic stress and depression ...[more]

PMID: 30276336

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Project description:We studied the effects of systemic infection on brain cytokine level and cerebral vascular function in Alzheimer's disease and vascular dementia, in superior temporal cortex (Brodmann area 22) from Alzheimer's disease patients (n = 75), vascular dementia patients (n = 22) and age-matched control subjects (n = 46), stratified according to the presence or absence of terminal systemic infection. Brain cytokine levels were measured using Mesoscale Discovery Multiplex Assays and markers of cerebrovascular function were assessed by ELISA. Multiple brain cytokines were elevated in Alzheimer's disease and vascular dementia: IL-15 and IL-17A were maximally elevated in end-stage Alzheimer's disease (Braak tangle stage V-VI) whereas IL-2, IL-5, IL12p40 and IL-16 were highest in intermediate Braak tangle stage III-IV disease. Several cytokines (IL-1β, IL-6, TNF-α, IL-8 and IL-15) were further raised in Alzheimer's disease with systemic infection. Cerebral hypoperfusion-indicated by decreased MAG:PLP1 and increased vascular endothelial growth factor-A (VEGF)-and blood-brain barrier leakiness, indicated by raised levels of fibrinogen, were exacerbated in Alzheimer's disease and vascular dementia patients, and also in non-dementia controls, with systemic infection. Amyloid-β42 level did not vary with infection or in association with brain cytokine levels. In controls, cortical perfusion declined with increasing IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13 and tumour necrosis factor-α (TNF-α) but these relationships were lost with progression of Alzheimer's disease, and with infection (even in Braak stage 0-II brains). Cortical platelet-derived growth factor receptor-β (PDGFRβ), a pericyte marker, was reduced, and endothelin-1 (EDN1) level was increased in Alzheimer's disease; these were related to amyloid-β level and disease progression and only modestly affected by systemic infection. Our findings indicate that systemic infection alters brain cytokine levels and exacerbates cerebral hypoperfusion and blood-brain barrier leakiness associated with Alzheimer's disease and vascular dementia, independently of the level of insoluble amyloid-β, and highlight systemic infection as an important contributor to dementia, requiring early identification and treatment in the elderly population.

Dataset Information

Cerebrovascular dysfunction with stress and depression.

Publications

Cerebrovascular dysfunction with stress and depression.

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