Cardiovascular System and Physical Activity

Question 1

What does the cardiovascula system include?

Answer 1

All blood vessels

Question 2

What useful processes and exchanges take place in microvascular networks and capillary beds?

Answer 2

Exchange of oxygen and glucose
Signalling molecules
Immune interactions
Clearance of waste products

Question 3

Maintaining cardiovascular health is about maintaining what?

Answer 3

Not just about maintaining blood vessels or heart health etc but importantly for brain health, its about maintaining the integrity of the microvascular network

Question 4

What does diseased or damaged vasculature impact

Answer 4

Transport of substances

Includes hormones and also nutrients and clearance of waste/toxic substances

Question 5

What are endothelial cells important for?

Answer 5

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

Question 6

What does it mean that the brain is highly metabolically activate but has limited storage?

Answer 6

Requires a constant clearance of waste products and constant blood flow for oxygen and glucose supply

Question 7

What is cardiovascular health intimately linked to?

Answer 7

The health of the brain and maintenance of normal function in brain circuits

Question 8

What diseases is neurovascular disruption implicated in?

Answer 8

AD
PD
Stroke
Neuroinflammation
Aging
Diabetes
Epilepsy

Question 9

What has been questioned?

Answer 9

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

Question 10

What has epidemiological evidence found?

Answer 10

That people who have cardiovascular disease are more at risk of a number of nuerological conditions, including AD

Question 11

What did Kulshreshthra et al. (2019) find?

Answer 11

Cardiovascular risk factors and cardiovascular disease positively associated with cognitive decline

risk factors =
Hypertension
Smoking
Diabetes
Obesity

Question 12

What did Barnes (2015) find?

Answer 12

Exercise (which reduces cardiovascular disease risk) is protective of cognitive function

Question 13

What did Kandola et al. (2016) find?

Answer 13

Exercise may also enhance cogntive function

• against this study is that its not enhancing but protective

Question 14

What has been associated with cardiovascular risk factors according to Boots et al. (2019)?

Answer 14

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

Question 15

What is an issue for many CNS diseases that invovle cogntitive decline?

Answer 15

Lack of effective treatments

Question 16

What did Wang et al. (2017) find?

Answer 16

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

Question 17

What is a limitation of Wang et al. (2017)

Answer 17

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

Question 18

What is important to consider about neuroimaging studies?

Answer 18

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

Question 19

What does this cumulative research so far suggest?

Answer 19

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)

Question 20

What is underlying these relationships between brain health and body health? Shabir et al. (2018)

Answer 20

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

Question 21

What else relates to endothelial cells? Dounavi et al. (unpublished)

Answer 21

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.

Question 22

What did Dounavi et al. find?

Answer 22

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

Question 23

What did Chhabria et al. (2018) examine?

Answer 23

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

Question 24

What did Chhabria et al. (2018) find?

Answer 24

Showed impacts on brain blood vessel development as well as vascular responses to sensory stimuli

High blood glucose impairs neurovascular function in zebrafish

Question 25

What did Chhabria et al. (2020) find?

Answer 25

Again found high blood glucose impairs neurovascular function in zebrafish by adding mannitol to the tank

robust responses to light flash in Mannitol group

Question 26

Why was Chhabria et al.’s research important?

Answer 26

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

Question 27

How does the brain affect cardiovasular function? Dampney et al. (2016)?

Answer 27

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

Question 28

How can stress be connected to cardiovascular disease?

Answer 28

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

Question 29

What is the main question?

Answer 29

Does cardiovascular function feedback more immediately to brain systems?

Question 30

What do we have in the body?

Answer 30

Visceral (internal organ) sensation and interoceptive input

Question 31

What is the brain aware of?

Answer 31

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

Question 32

What else is the brain aware of?

Answer 32

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

Question 33

What did Critchley & Harrison (2013) find?

Answer 33

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

Question 34

What is the importance of brain-gut interactions

Answer 34

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

Question 35

Why do exercise effects potentially lead to improvments in brain function?

Answer 35

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

Question 36

Why must we be careful in assuming exercise increases brain function?

Answer 36

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.

Question 37

What did Greenwood (2019) find?

Answer 37

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

Question 38

Why is Greenwoods finding important?

Answer 38

Because many studies do not include consideration of reward/dopamine related effects of physical activity e.g. Stimpson et al. (2018)

Question 39

What is the mechanism of exercise that affects the HPA axis?

Answer 39

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)