Cardiovascular System Flashcards
What is the link between cardiovascular health and brain health?
The route for several key areas of brain-body communication is not entirely reliant on nerve cells and pathways
It is also reliant on the vascular system and the blood brain barrier
Cardiovascular system includes all the blood vessels and all those vessels in the brain
Diseased or damaged vasculature impacts on transport of substances - this includes hormones but also nutrients and clearances of waste/toxic substances
Is the brain microvasculature part of the cardiovascular system?
Yes
Brain has limited storage capacity - as a highly metabolically active organ, it also requires constant waste clearance
The health of the brain and the maintenance of normal function in brain circuits is thus intimately linked to cardiovascular health
What is the neurovascular unit?
Interconnected system of neurons, astrocytes, pericytes and vascular cells (endothelial cells in particular)
Neurovascular unit provides the basis of the blood-brain barrier - underpins neurovascular function and neurovascular coupling
What is the link between brain disease and neurovascular function?
There is an increasing recognition of neurovascular disruption in many CNS diseases
What comes first? - Is brain disease causing neurovascular disruption or is it neurovascular disruption causing brain disease?
What diseases are linked to neurovascular disruption?
Normal ageing
Brain metastases
Neurotransmitter disturbance
Alzheimers disease
Stroke
Epilepsy
Neuroinflammation
Is there a link between cardiovascular health and cognitive function?
There is epidemiological and associative evidence of a link
Kulshreshthra et al (2019) - cardiovascular risk factors and cardiovascular disease positively associated with cognitive decline
i.e., hypertension, smoking, diabetes, obesity
Barnes et al. (2015) - exercise which reduces cardiovascular disease risk is protective of cognitive function
Kandola et al. (2016) - exercise may also enhance cognitive function
How does cardiovascular health affect connectivity and function of the brain?
Boots et al. (2019) - Cognitive and connectivity changes associated with CV risk factors in neurologically normal adults
Cardiovascular disease risk is associated with various cognitive functions and this relationship is mediated by connectivity strength in specific brain structures
What increases and decreases risk of cognitive decline?
Baumgart et al. (2015)
Increase risk
- TBI (strong evidence)
- Mid life obesity (strong evidence)
- Mid-life hypertension (strong evidence)
- Current smoking (strong evidence)
- Diabetes (strong evidence)
- History of depression (lower evidence)
- Sleep disturbances (lower evidence)
Decrease risk
- Years of formal education (strong evidence)
- Physical activity (strong evidence)
- Mediterranean diet (moderate evidence)
- Cognitive training (moderate evidence)
- Moderate alcohol consumption (lower evidence)
- Social engagement
What increases and decreases risk of dementia?
Baumgart et al. (2015)
Increase risk
- TBI (strong evidence)
- Mid-life obesity (moderate evidence)
- Mid-life hypertension (moderate evidence)
- Current smoking (moderate evidence)
- Diabetes (moderate evidence)
- History of depression (unclear evidence)
- Sleep disturbances (unclear evidence)
Decrease risk
- Years of formal education (strong evidence)
- Physical activity (moderate evidence)
- Mediterranean diet (lower evidence)
- Cognitive training (lower evidence)
- Moderate alcohol consumption (unclear evidence)
- Social engagement (unclear evidence)
What is the link between physical activity and cognitive function?
Lots of neuroimaging studies showing changes in functional connectivity following exercise interventions
Weng et al. (2017)
30 mins of moderate intensity aerobic cycling selectively increased synchrony among brain regions associated with affect and reward processing learning and memory and in regions important for attention and executive control
What is an issue with Weng et al. (2017)?
What if you consider that functional neuroimaging signals themselves are a product of the brain vasculature
It is not easy to tease this apart from the extent to which they provide an index of brain activation and connectivity
Altered vascular reactivity could lead to an apparent reduction in activation when neuronal function remains normal
Explain the pathway that vascular factors effect
Complex set of potential pathways
Focused on the neurovascular unit and endothelial cells e.g. endothelial cell dysfunction is a known feature of diabetes, atherosclerosis, hypertension etc
Endothelial cells a core element of macro- and micro- vasculature as well as the blood brain barrier
What other factors cause neurovascular breakdown?
Environmental factors = air pollution, low vitamin D
Genetic risk factors = APPSw, APOE4, PSENI
Lifestyle factors = diet, exercise, smoking
What cells are the core element of macro-, micro-vasculature and the BBB?
Endothelial cells
What conditions have endothelial cells been implemented in?
Endothelial cell dysfunction is a known feature of diabetes, atherosclerosis, hypertension
What did Dounavi et al find regarding the role of brain vascular function in diabetes?
Multimodal neuroimaging investigation of brain vascular responses
Comparison of healthy controls, diabetic patients and impaired glucose tolerance patients
Found altered cerebral haemodynamics in impaired glucose tolerance and type 2 diabetes revealed using multi time point aterial spin labelling
Wide range of changes in how blood is delivered to tissue in those with IGT and T2DM
Potential for neuroimaging biomarkers of neurological risks in diabetes
What are the effects of glucose on neurovascular function in zebrafish?
Chhabria et al (2018)
Development of a zebrafish model to study the impact of altered neurovascular function on brain function and cognition
Huge potential to explore gene interactions and molecular signalling pathways using zebrafish
Transparent when young so can image them easily
Showed impacts on brain blood vessel development as well as vascular responses to sensory stimuli
High blood glucose impaired neurovascular function
What brain systems control cardiovascular function?
Cortical - cortex
Subcortical - thalamus, amygdala, hippocampus
mid brain, hypothalamus (hormone release)
Brainstem - pons/medulla
control sympathetic activity, respiratory activity (autonomic nervous system)
Motor activity (freezing)
How is stress related to cardiovascular function/disease?
Brain circuits controlling cardiovascular function do so via activation of the autonomic nervous system
These circuits receive input from cortical and subcortical systems and are responsive to a wide range of physiological and psychological stimuli
This links back to stress
The continued presence of stressors can increase the presence of cardiovascular risk factors and lead to cardiovascular disease
What are the mechanisms of stress on cardiovascular function?
Stress causes a physiological response which acts on the HPA axis, the sympathetic nervous system, stress-responsive humoral factors
The sympathetic nervous system causes increased oxygen consumption, increased blood pressure, increased heart rate, links to thrombosis and coagulation which can cause cardiovascular disease
The HPA axis causes changes in glucose metabolism - impaired glucose tolerance, insulin resistance
Changes to lipid metabolism
Links to obesity
All risk factors for cardiovascular disease
What are the feedback loops between the brain and cardiovascular system?
Brain circuits for cognition and affect link to hormone and endocrine systems and the autonomic nervous system
Autonomic nervous system and endocrine system link to the cardiovascular system
cardiovascular system links to brain health which links back to brain circuits for cognition and affect
What are the mechanisms of cardiovascular system feedback to brain systems?
Stress related modulation of cardiovascular and metabolic function can feedback to the brain e.g., cortisol related amygdala or hippocampal activation
Also, visceral (internal organs) sensation and interoceptive input - the brain receives ongoing input regarding body state via visceral sensory afferents and via sensing of blood-borne chemical - this underpins interoceptive input to brain systems at multiple levels
Inflammation and sickness behaviour
Brain-gut interactions
What is interoception?
Interoception means sensing internal signals from your body, like when you are hungry, when your heart is beating fast, or when you need the toilet
How do brain-gut interactions affect brain function?
Morera et al. (2019)
The mechanisms underlying microbiota-gut-brain axis communication involves neuro-immune-endocrine mediators
This interconnected network includes the central nervous system (CNS), the autonomic nervous system, the enteric nervous system and the HPA
Changes in gut microbiome composition has been already related to cognitive disorders and mental illness
How does exercise effect brain health?
Stimpson et al. (2018)
Physical activity increases cardiovascular fitness, improving cerebral circulation (eNOS increases, CBV increases)
This leads to the upregulation of neurotrophins and supporting factors increasing brain plasticity
Brain plasticity induces structural changes and functional enhancement of new neurons giving cognitive benefits
How does exercise act as a stress buffer?
Zschuke et al. (2015)
Reduced stress reactivity may constitute a mechanism of action for the beneficial effects of exercise in maintaining mental health
Participants with a higher aerobic fitness showed lower cortisol responses to the MIST (stress task)
Acute aerobic exercise reduces the neural and cortisol stress response to the MIST
The magnitude of mood and endocrine changes observed correlated with brain activation magnitude
Acute stress-buffering effect of exercise relies on negative feedback mechanisms
