Cardiovascular System and Physical Activity Flashcards
What does the cardiovascula system include?
All blood vessels
What useful processes and exchanges take place in microvascular networks and capillary beds?
Exchange of oxygen and glucose
Signalling molecules
Immune interactions
Clearance of waste products
Maintaining cardiovascular health is about maintaining what?
Not just about maintaining blood vessels or heart health etc but importantly for brain health, its about maintaining the integrity of the microvascular network
What does diseased or damaged vasculature impact
Transport of substances
Includes hormones and also nutrients and clearance of waste/toxic substances
What are endothelial cells important for?
The lining of blood vessels, they are the primary barrier through which the exchange of various substances and molecules takes place
Also important in the signalling cascade for the change in blood flow in the brain
What does it mean that the brain is highly metabolically activate but has limited storage?
Requires a constant clearance of waste products and constant blood flow for oxygen and glucose supply
What is cardiovascular health intimately linked to?
The health of the brain and maintenance of normal function in brain circuits
What diseases is neurovascular disruption implicated in?
AD
PD
Stroke
Neuroinflammation
Aging
Diabetes
Epilepsy
What has been questioned?
What comes first:
Cell/synaptic loss
or
Disruption of neurovascular function
May not be the first thing to happen but when there is some disease related disruption it can trigger some neurovascular effects that make the disease worse
What has epidemiological evidence found?
That people who have cardiovascular disease are more at risk of a number of nuerological conditions, including AD
What did Kulshreshthra et al. (2019) find?
Cardiovascular risk factors and cardiovascular disease positively associated with cognitive decline
risk factors =
Hypertension
Smoking
Diabetes
Obesity
What did Barnes (2015) find?
Exercise (which reduces cardiovascular disease risk) is protective of cognitive function
What did Kandola et al. (2016) find?
Exercise may also enhance cogntive function
- against this study is that its not enhancing but protective
What has been associated with cardiovascular risk factors according to Boots et al. (2019)?
Cognitive and connectivity changes
Cardiovascular disease risk is associated with various cognitive functions and this relationship is mediated by connectivity strength in specific brain structures
White matter pathways seem to mediate cv risk factors and neurological decline
What is an issue for many CNS diseases that invovle cogntitive decline?
Lack of effective treatments
What did Wang et al. (2017) find?
Neuroimaging study
changes in functional connectivity following exercise interventions
30 minutes 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 a limitation of Wang et al. (2017)
Just because you change connectivity doesn’t mean you change cognitive function
paper doesn’t discuss performance, e.g. whether learning or memory or cogntive function increased
What is important to consider about neuroimaging studies?
Functional neuroimaging signals are themselves 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
e.g. altered vascular reactivity could lead to an apparent reduction in activation when neuronal function remains normal
What does this cumulative research so far suggest?
That the integrity of brain circuits is affected by the health of the cardiovascular system, not just in relation to disease, but also in preclinical stages and possibly in healthy individuals (e.g. effects of exercise)
What is underlying these relationships between brain health and body health? Shabir et al. (2018)
Complex set of potential pathways: vascular, exnvironmental, genetic risk and lifestyle factors
Focused on the neurovascular unit and endothelial cells (as a key interface betweeen blood and brain)
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 else relates to endothelial cells? Dounavi et al. (unpublished)
Diabetes
Multimodal neuroimaging investigation of brain vascular responses
Comparison of healthy controls, diabetic patients (T2DM) and impaired glucose tolerance patients (IGTpre-diabetes)
Detailed assessment of many vascular parameters with machine learning applied to determine group differences
Altered cerebral hemodynamics in impaired glucose tolerance and type-2 diabetes revealed using multi-time-point arterial spin labeling.
What did Dounavi et al. find?
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 did Chhabria et al. (2018) examine?
The effect of hyperglycemia on neurovascular coupling and cerebrovascular patterning in zebrafish
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 and they have a neurovascular system
Added glucose into the tank to induce hyperglycemia
What did Chhabria et al. (2018) find?
Showed impacts on brain blood vessel development as well as vascular responses to sensory stimuli
High blood glucose impairs neurovascular function in zebrafish
What did Chhabria et al. (2020) find?
Again found high blood glucose impairs neurovascular function in zebrafish by adding mannitol to the tank
robust responses to light flash in Mannitol group
Why was Chhabria et al.’s research important?
It validated the use of zebrafish to understand how conditions like diabetes might impact upon brain health
and this is a stepping stone to understanding how this might play out in cognitive decline
How does the brain affect cardiovasular function? Dampney et al. (2016)?
The brain controls cardiovascular function in a way which bring in many different brain areas
Although ultimately you have hindbrain areas that control breathing and can regulate heartrate, these regions receive input from a much wider brain network
This could explain why heart rate may be continually elevated in a defence mode, in a situation of chronic stress
Seemingly have a direct route in the brain
How can stress be connected to cardiovascular 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
Physiological: body temperature, blood pressure, blood oxygenation
Psychological: stressors (external stimuli, cognitive-affective processes)
The continued presence of stressors can increase the presence of cardiovascular risk factors and lead to cardiovascular disease
Behavioural responses may relate directly to cardiovascular responses e.g. if stressed, might not engage in sufficient levels of physical activity= reduced activity= exacerbates cardiovascular function or eating behaviour as well
see diagram in lecture
What is the main question?
Does cardiovascular function feedback more immediately to brain systems?
What do we have in the body?
Visceral (internal organ) sensation and interoceptive input
What is the brain aware of?
Ongoing sensory input relating to its own internal status
The brain receives ongoing input regarding body state via visceral sensory afferents and via sensing of blood-borne chemicals
This underpins interoceptive input to brain systems at multiple levels
Brain is aware of the cardiac cycle, what your heart rate is, it regulates heart rate but then the sensation of that sort of thing e.g. the sensation of the current state of digestion, this information is going back into the brain both through direct nervious system signalling, but also through the presence of blood borne chemicals as well, so oxygenation levels of the blood is something the brain is aware of
What else is the brain aware of?
Inflammation and indications of sickness or disease, so if there is systemic inflammation in the body that might occur in repsonse to injury or infection, the brain is aware of that, it gets that information and then it will alter behaviour in order to cope with that
What did Critchley & Harrison (2013) find?
Giving an individual sensory stimulation and the way in which particualr regions of the brain respond to that depend on exactly what point of the cardiac cycle the arrival of that sensory input is
What is the importance of brain-gut interactions
Have the same interoceptive information coming from the gut , stuff to do with the activation of smooth muscle cells and things relationg to measures e.g. glucose measures in the blood, but the interaction between the brain and the gut is actually complicated because as well as the physiological/biological processes of digestion that are happening in the gut, there is also the gut microbiota e.g. flora and fauna that exist in the gut that help or hinder digestion, as they release chemicals that can get into the blood stream that can influence behaviour through the brain, we are to some extent behvaing at the will of the gut bacteria we have
Why do exercise effects potentially lead to improvments in brain function?
Could be due to physiological changes
e.g. angiogenisis- the development of blood vessels, could relate to improvments in blood flow in the brain, improvements in plasticity
These changes connect body health and brain health
Why must we be careful in assuming exercise increases brain function?
Must think about other pathways involved
We know exercise alters domapine signalling, this affects reward circuitry in the brain, might change the way you respond to aversive or rewarding stimuli and that changes behaviour which plays out in different ways in terms of cogntive function, it hard to know.
What did Greenwood (2019) find?
Exercise alters DA signalling to increase reward related responses – buffering the effects of aversive stimuli
If you are more resilient to aversive stimuli, you may find that it impacts on the way that stress can feed through physiological responses and potentially propagate things around cardiovascular disease
so the reward/aversive response modulation by exercise can affect different things which is separate to the way exercise might just affect oxygenation of blood in the brain
Why is Greenwoods finding important?
Because many studies do not include consideration of reward/dopamine related effects of physical activity e.g. Stimpson et al. (2018)
What is the mechanism of exercise that affects the HPA axis?
Exercise augments/bolsters negative feedback in the HPA axis
It’s been found that the critical factor for the termination of a stress response in the HPA axis is negative feedback, more effective negative feedback should in theory enable you to limit stress responses and contain them more effectively
Exercise reduced the neural and cortisol response to a stressful stimulus
The magnitude of mood and endocrine changes observed correlated with brain activation magnitude.
This could be what exercise is doing, dampening down the stress response
- Zschucke et al. (2015)
