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BMS3052 > WEEK 11 COMOBIDITIES CONTINUED > Flashcards

WEEK 11 COMOBIDITIES CONTINUED Flashcards

1
Q

What conditions do people have if they are at increased risk of getting covid-19?

A
  • Heart failure. CID, cardiomyopathies
  • COPD
  • Obesity
  • Other chronic diseases.
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2
Q

What conditions do people have that means they MAY be at increased risk of getting covid-19?

A
  • Overweight
  • Have asthma
  • Hypotensive.
  • Have a neurological conditions such as dementia.
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3
Q

What percentage of countries have no mental health legislation?

A
  • 25%
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4
Q

What % of countries have no mental health policy or no mental health program respectively?

A
  • More than 40% with no mental health policy and over 30% with no mental health programme.
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5
Q

What % of countries surveyed have indicated that the COVID-19 pandemic has disrupted mental health serives?

A
  • 93%
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6
Q

Over the COVID-19 lockdown period in Australia, how had mental health problems changed in prevalence (nationwide survey), and what types of people was this worse for?

A
  • Mental health problems Dubbo with and prevalence compared to normal Lockdown periods.
  • This was due to anxiety, depression and irritability attributed to restrictions
  • Worse for those who:
  • Lost jobs
  • Caring for children and other family members
  • Lived alone
  • Had fewer resources
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7
Q

Would extending Telehealth be suitable for all people in lockdown?

A
  • NO
  • ## This is because some people are from low socioeconomic areas and there may be less privacy at home.
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8
Q

In a study by Stanton et al., what was decreased and increased in terms of changes linked to higher anxiety in the first lockdown period for COVID-19?

A
  • A decrease in physical activity
  • Increase in alcohol use
  • Increase in smoking
  • Increase in Psychological distress
  • These changes are ALL linked to higher depression and anxiety
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9
Q

What 4 other factors were seen in those who had higher psychological distress as part of the Stanton et al study. (W11 L1)?

A
  1. More females compared to males
  2. Singled compared to partnered
  3. Lower incomes
  4. Increase in chronic illness
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10
Q

With a study conducted via the Kids helpline (aged 18-25), what were the 5 top concerns across the age range from Jan-April 2020?

A
  1. Mental health
  2. Social isolation
  3. Impacts on education.
  4. Impact on family life.
  5. Changes to plans and activities.
    - Greater burden to carers looking after autistic people
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11
Q

What 3 things is Australia doing to improve mental health services from 2020 onwards?

A
  1. Launched a mental health and well-being plan in May 2020. (Additional $48 million mental health funding)
  2. Increased access to Medicare subsidized psychological sessions (Up to 20 from 10) in Oct 2020
  3. Additional, mental health clinics in Victoria (Sept 2020)
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12
Q

Do many people with autism like structure and routine?

A
  • YES
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13
Q

Even though every autistic person is different what three things can autism be a company by in terms of behaviours?

A
  • Anxiety
  • Irritability
  • Agression
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14
Q

In an Italian survey of parents of young children with autism, what was the biggest request coming out of life in covid lockdown?

A
  • Request for in home healthcare support (30%) and Centre-based healthcare support (10.5%)
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15
Q

What was a concern and thus suggestion made for people with autism regarding the COVID-19 pandemic?

A
  • To have a home testing kit
  • This is because they don’t understand the concept of wearing a mask and also difficult if they have to go into emergency without carers.
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16
Q

What does an Autistic person find it hard to do in terms of tasks?

A
  • They find it hard to switch tasks and so need time to process
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17
Q

Is Asthma more prevalent in boys or girls aged 0 to 14?

A
  • More prevalent in boys aged 0-14
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18
Q

Is asthma more prevalent in males or females age 15 and over?

A
  • More prevalent in females aged 15 and over
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19
Q

What is the estimated cost of asthma in Aus?

A
  • $27.9 billion (as of 2015) - 3.3B in economic costs + 24.7 in “burden of disease”
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20
Q

What is the prevalence of asthma in australia?

A
  • 1/10 Aussies
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21
Q

What is the estimated healthcare costs of obesity?

A

-27.9 billion (as of 2017)

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22
Q

Who is the 13th fattest country in the world?

A
  • Australia
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23
Q

What % of children are classified as overweight?

A
  • 25%
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24
Q

How many Aussies are overweight and obese respectively?

A
  • > 6M overweight and >5.2M obese
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25
Q

What are the comorbidities that come with Obesity?

A
  • hypertension
  • diabetes
  • GERD
  • OSA
  • Asthma
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26
Q

What is the most common type of Asthma?

A
  • Allergic asthma (T2 type asthma)
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27
Q

What are the two different types of asthma umbrellas?

A
  • T2-type asthma (allergic and exercise induced)

- Non-T2 type asthma (obesity associated, smoking related etc)

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28
Q

Does obesity increase the risk of asthma occurring?

A
  • YES
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29
Q

Is the obesity and asthma relationship a dose dependent response?

A
  • YES
    e. g. Increasing BMI is associated with increasing odds of asthma (e.g. 40% higher risk of developing asthma if you are OVERWEIGHT AND 90% higher risk with obese etc. )
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30
Q

How can obesity both cause and complicate asthma?

A
  • It can worsen the asthma consequent to obesity and can also cause Non-T2 type asthma, which is also worsened by obesity.
  • Allergic asthma is also worsened by obesity
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31
Q

Which is the main immune cell infiltration in T2-Type asthma?

A
  • Eosinophils
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32
Q

Which is the main immune cell infiltration in Non-T2 type asthma?

A
  • Neutrophils
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33
Q

What are the 4 common features of asthma fitting under the inflammation and remodeling umbrella?

A
  1. Inflammatory cell infiltration. (eosinophils- T2, neutrophils- Non-T2)
  2. Excessive mucus (obstruction and barrier to inhaler therapy)
  3. Basement membrane thickening (fibrosis)
  4. More smooth muscle (increased contraction)
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34
Q

Which two factors lead to the airways contracting “too easily and too much” in terms of airway hyperresponsiveness?

A
  • The influence of inflammatory mediators

- Increased bulk of “sensitised” muscle

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35
Q

How is AHR (Airway hyperresponsiveness) quantified?

A
  • Need to find a dose of bronchoconstrictor that causes a 20% increase in airway resistance (methylcholine challenge).
  • Don’t want to push someone too much.
  • The lower the PC20 value is (graph), the more severe someone’s asthma is, and the more hyper-responsive their airways are.
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36
Q

What does a low PC20 value mean?

A
  • that a person’s asthma is more severe and the more hyperresponsive their airways are
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37
Q

What are the factors that Th2 cells release in terms of allergic asthma and causing T2 immune deviation to aeroallergens?

A

-IL-5, IL-4 and IL-13

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38
Q

What are the factors that Eosinophils cells release in terms of allergic asthma and causing T2 immune deviation to aeroallergens?

A
  • Leukotrienes

- Cytokines

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39
Q

What are the factors that Plasma cells and mast cells release in terms of allergic asthma and causing T2 immune deviation to aeroallergens?

A
  • IgE

- Histamine, Leukotrienes and cytokines

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40
Q

What are the three main types of immune cells/mediators in Obese asthma (known as T1 immune deviation or ‘non T2)?

A
  1. Increased adipose tissue - adipokines (more leptin-pro inflamm, and less adiponectin- antiinflamm)
  2. Increase in macrophages
  3. Increase in neutrophils (TNFa, IL-6, and IL-17)
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41
Q

Are relievers or preventers used for obese (non T2) type asthma, which phase of asthma do they target, and what do they relieve?

A
  • Relievers are used as it is non allergic asthma
  • They target the immediate (acute) phase of asthma
  • They relieve airway smooth muscle spasm
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42
Q

What are examples of relievers used to treat Obese asthma?

A
  • B2 adrenoceptor agonists
  • PDE inhibitors
  • Muscarinic receptor antagonists
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43
Q

What is an example of a B2 adrenoceptor agonist (1st line treatment for non T2/obese type asthma and what is its mechanism of action?

A
  • SABA- Salbutamol , (LABA-fromoterol)
  • This mimics adrenaline
  • Increases cAMP synthesis
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44
Q

What is an example of a PDE inhibitor treatment for non T2/obese type asthma and what is its mechanism of action?

A
  • Theophylline

- Decreases the cAMP breakdown

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45
Q

What is an example of a muscarinic receptor antagonist for non T2/obese type asthma and what is its mechanism of action?

A
  • SAMA- ipratropium, LAMA-tiotropium
  • Block Ach (PNS)
  • Decrease calcium signaling
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46
Q

What are the limitations with relievers, specifically B2 adrenoceptor agonists (1st line treatment)?

A
  • Efficacy reduced if airway contraction is INCREASED (functional antagonism) or if B2 adrenoceptor expression is reduced
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47
Q

What is an example of preventers and their mechanism of action?

A
  • Example is Inhaled corticosteroids (fluticasone, budesonise (regulate gene transcription)
  • For TRANSACTIVATION: bind to GREs, increase anti-inflammatory proteins (annexin A1)
  • For TRANSREPRESSION: bind to TFs and decrease pro inflammatory proteins e.g. COX-2, IL-1 and TNFa
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48
Q

Are preventers (i.e. inhaled corticosteroids) helpful in non-T2 Asthma (Obese asthma) and why is/isn’t this the case?

A
  • NO
  • This is the case as the main cells in non-T2 type asthma are neutrophils, TNFa and IL-17 (compared to eosinophils, Th2 cytokines)
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49
Q

Can preventers (i.e. inhaled corticosteroids) be used in combination with a LABA for long-term bronchodilation, and if so, are there any limitations?

A
  • Yes it may be used
  • BUT the dilator efficacy may be reduced (like SABA) if the contraction is increased (functional antagonism) and B2 adrenoceptor expression is reduced
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50
Q

What are the three main mechanisms of obese asthma?

A
  1. Decreased lung function.
  2. Inflammation
  3. Oxidative stress
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51
Q

What is included in decreased lung function in terms of asthma and obesity mechanisms?

A
  • Reduced FRC and ERV due to abdominal adiposity (adipodisity linked)
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52
Q

What are three components of inflammation that occurs in obese (non-T2 type) asthma?

A
  • Th1 related inflammation in the airways
  • Increased Leptin in the airways, reduced adiponectin
  • IL-17 associated inflammation in the airways
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53
Q

What is one component of oxidative stress that occurs in obese (non-T2 type) asthma?

A
  • Low L-arginine ADMA ratio and increased oxidative stress and lower NO
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54
Q

Does obesity impair lung function?

A
  • YES
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55
Q

How does obesity impair lung function?

A
  • Decreases the tidal volume (TV) (increased rate) which contributes an increase in airway stiffness (because they are not relaxing and contracting to their full capacity, making it harder to breathe). This then leads to an increase in airway contraction and increase in airway narrowing.
  • So:
    DECREASED TITAL VOLUME
    INCREASED AIRWAY STIFFNESS
    INCREASED AIRWAY CONTRACTION
    INCREASED AIRWAY NARROWING
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56
Q

As Obesity impairs lung function, does it impact on the airway obstruction, and what does this mean?

A
  • NO it does NOT impact on airway obstruction. This means that the FEV1/FVC are preserved (not changed)
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57
Q

How does obesity cause systemic inflammation (i.e. what are the factors that are released?)

A
  • Increased Prime lemon tree leptin decrease anti-inflammatory adiponectin.
  • Macrophages infiltrate adipose and release tissue release TNF-a and IL-6.
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58
Q

How does obesity cause lung inflammation (i.e. what are the three things that occur) ?

A
  • Decreased airway eosinophils (lumen. sputum)
  • Increased airway neutrophils
  • Predominately Th-1 and potential IL-17 related inflammation
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59
Q

Via which pathway is interrupted to allow for inflammation and bronchodilation?

A
  • L-arginine to cNOS (activates NO)
  • NO + L-citrulline causes inhibition of inflammation bronchodilation
  • BUT in Obesity asthma, something happens to the cNOS enzyme and there is no more inhibition of inflammation bronchodilation
  • Obesity REDUCES NO-
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60
Q

Are there increased levels of ADMA in obesity, and if so, what is the mechanism and result of this?

A
  • YES there are
  • ADMA- assymetric di-methyl arginine that is an endogenous inhibitor of NOS enzymes that produce NO -
  • It increases and INHIBITS THE cNOS enzyme wihch causes NO production (therefore loss of protection) to cause inflammation, increased contractility and cytotoxicity.
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61
Q

What is ADMA?

A
  • Asymmetric di-methyl arginine

- Endogenous inhibitor of NOS enzymes that produce NO

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62
Q

Are there increased levels of iNOS in obesity and if so, how dos this contribute to the increased oxidative stress?

A
  • YES
  • iNOS produces O2- which combines with NO and Citrulline to form a powerful oxidant that causes inflammation, increased contractility and cytotoxicity much like ROS does
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63
Q

Are there increased levels of Arginase I in obesity, and if so, what is the mechanism of action?

A
  • YES (this is the enzyme that breaks arginine down)
  • Increased Arginase, leads to urrea and L-orthinine
  • This leads to polyamines and L-proline being produced.
    1. Polyamines lead to airway smooth muscle proliferation which leads to airway remodelling
    2. L-proline leads to collagen production which also leads to airway remodelling (via fibrosis)
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64
Q

What are the three main mechanisms of obese asthma and what are the details of these?

A
  1. IMPAIRED LUNG FUNCTION:
    - Increase abdominal fat, decrease tidal volume–] airway narrowing
  2. INFLAMMATION
    - Increased leptin, decreased adiponectin
    - increased non T2 inflammation- neutrophils, TNF-a, IL-6 and IL-17
  3. OXIDATIVE STRESS
    - Increased ADMA (cNOS inhibitor), arginase –> decreased NO& L-Arg, increased ROS –> decreased bronchodilation, increased inflammation and remodeling
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65
Q

What may be 5 additional factors contributing to asthma and obesity?

A
  • Genetic susceptibility
  • Birth weights – low or high?
  • Prenatal, maternal and paternal nutrition, postnatal diet
  • Gender?
  • Comorbidities (obstructive sleep apnea).
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66
Q

What did a study find in relation to males, weight and asthma risk, and what may be the implications?

A
  • They found that if the males gained the weight in their childhood it increased the risk of their offspring in the future becoming asthmatic as adults.
  • Therefore may want to think about being healthy in long term.
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67
Q

Is there conclusive evidence that gender contributes to obese asthma?

A
  • NO

- One study did not find any major differences between the sexes

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68
Q

Does obesity reduce responsiveness to asthma therapy, and if so which are the two main classes it has a reduced resposne against?

A
  • YES
    1. Dilators
    2. Steroids
69
Q

In which 3 ways does obesity reduce responsiveness to dilator therapy?

A
  • Decrease the tidal volume, increases airway narrowing.
  • Decreases NO and decreases bronchodilation.
  • Decreases progesterone (steroid) levels, reduces B2 Adrenoceptor function.
70
Q

Has steroids affecting B2 adrenoceptor expression and function been clinically confirmed?

A
  • NO

- One study found that progesterone decreased B2 adrenoceptor expression, leading to relaxation

71
Q

Does obesity reduce the dilator response in just non-T2 type asthma?

A
  • NO

- It reduces the response in both types of asthma (T2 and non T2)

72
Q

Do people with COPD and asthma have much of a response to a B agonist?

A
  • NO and not much reversibility

- Because COPD doesn’t yield much of a response. Photo keep repeating themselves. Right

73
Q

Do steroids have good efficacy in non-T2 type asthma?

A
  • NO, obesity further reduces this
74
Q

Does obesity reduce the steroid response in T2 type asthma and further reduce the response in non-T2 type asthma?

A
  • YES
75
Q

Does obesity reduce the responsiveness to anti-inflammatory therapy for MILD asthma?

A
  • YES

- % of asthma controlled days decreased with increasing BMI

76
Q

In a trial looking at the effect of NON SURGICAL weight loss in obese asthma, was there an improvement of asthma with weight loss?

A
  • A weight loss of > 10% or greater showed improvement in Asthma Control Questionnaire (ACQ) in those with uncontrolled asthma
  • Modest effect but suggests that losing weight could be a benefit. Bigger trial with more subjects with a bigger impact on weight loss will confirm this.
77
Q

In one study looking at the effects of bariatric surgery on weight loss in obese asthma, what were the results in terms of PC20, FEV1/FVC, Adiponectin and Leptin?

A
  • The PC20 ([methylcholine] that makes airway resistance increase by 20%) increased 2fold after having the surgery so a massive reduction in airway hyperresponsiveness. Because patients needed 2x as much methacholine to give a 20% increase in airway resistance.
  • Improvement in FEV1, and FVC (both of those change in the same direction).
  • Adiponectin went up both in lung and serum (which is good) Despite the reduction in fat, the cytokine levels increased.
  • Leptin were NOT decreased in the lung but WERE decreased in the serum. But overall favouring anti inflammatory effect as there are increased levels of adiponectin.
78
Q

What does a LOW PC20 indicate?

A
  • AHR (Airway hyperresponsiveness)
79
Q

Did weight loss from surgery impact on hyperresponsiveness for those that were overweight AND with allergic asthma?

A
  • NO

- It impacted for those that were overweight but NOT those overweight with allergic asthma as well.

80
Q

Which neuroprotective mechanism is a huge challenge with ischaemic stroke?

A
  • Excitoxtoxicity
81
Q

What is an example of a genetic mutation cnausing a neurodegenerative disease?

A
  • Change in superoxide dysmutase to cause MND
82
Q

What do you have to be careful about when looking at targeting the anti-apoptotic mechanisms for neuronal regeneration?

A

-You don’t want the cells to become cancerous (teratomas)

83
Q

When looking at neuroregenerative mechanisms, what should you pair the increasing endogenous stem cells with and why?

A
  • Should pair the increasing endogenous stem cells with Angiogenesis
  • This is because you can traffic stem cells BUT still need a blood supply for them, hence angiogenesis
84
Q

What is the gut-brain axis defined as?

A
  • A bidirectional link between the CNS and the enteric nervous system of the body.
  • It involves the complex crosstalk between the endocrine (hypothalamic-pituitary-adrenal axis), immune (cytokine and chemokines) and the autonomic nervous system.
85
Q

Is the gut-brain-axis only gut-brain communication?

A
  • NO

- It is also endocrine, immune, ANS etc

86
Q

What are four examples of influences that the brain has on the gut?

A
  1. Motility
  2. Secretion
  3. Nutrient delivery
  4. Microbial balance
87
Q

What are 4 examples of influences that the gut has on the brain?

A
  1. Types of neurotransmitters
  2. Stress/anxiety
  3. Mood
  4. Behaviour
88
Q

What influences the newborns microbiota signature?

A
  • The way it was delivered e.g. Vaginal or caesarian
89
Q

What have studies shown the gut microbiota is central to in the first few post natal weeks?

A
  • Central to the development and maturation of the human CNS and ENS in the early post natal weeks
90
Q

Which 6 pathways do the microbes of the gut microbiota interact with the gut-brain axis?

A
  1. The vagus nerve
  2. Neuroendocrine (gut hormone) signalling
  3. Interference with Tryptophan metabolism (involved with Serotonin and Melotonin)
  4. The immune system
  5. Altered intestinal permeability
  6. Production of microbial metabolites (based on the microbiome- microbiota producing different factors)
91
Q

Have short chain fatty acids (SCFAs) been shown to generate neural GENERATION in terms of stroke outcomes?

A
  • YES
92
Q

Where are a significant amount of amyloids found in terms of the gut-brain axis lecture?

A
  • In the gut microbiota
93
Q

What does the production of amyloid proteins help bacterial cells to do?

A
  • It helps the bacterial cells bind to each other forming biofilms and to resist destruction by physical or immune factors (Amyloid biofilms)
94
Q

How different are the bacterial amyloids from the CNS amyloids, and do they share any similarities?

A
  • They differ in their primary structure BUT share similarities in their tertiary structure
  • Also similarities in the singaling e.g. both CNS and bacterial signal via TLR2 pathway
95
Q

What are examples of Curli producing bacteria and what does it mean to say ‘Curli bacteria’?

A
  • Enterobacteria such as E.coli and Salmonella

- Curli bacteria are those that produce the extracellular amyloid protein fibre ‘Curli’.

96
Q

In the brain of animals exposed to curli producing bacteria, what is there an increased expression of and what can this indicate?

A
  • Increased expression of TLR2, IL-6 and TNFa.
  • Both bacterial and CNS amyloids signal via TLR2 pathway
  • This can indicate that there may be a relationship between the gut microbiota and the amyloid plaques in those patients suffering from Alzheimer’s disease.
97
Q

What do rats exposed to bacteria expressing Curli have enhanced levels/amounts of?

A
  • Rats exposed to bacteria expressing Curli have enhanced levels of Alpha Synuclein Deposition in the brain and gut neurons
98
Q

In a study by Chen et al (2016) looking at rats exposed to Curli producing bacteria, what did they find?

A
  • They displayed increased neuronal alpha-synuclein (a-syn) deposition in both the gut and brain, and enhanced microgliosis and astrogliosis compared to rats exposed to bacteria without the ability to produce Curli protein
  • There might be a relationship for these bacteria that cold be generating these amyloids to triggering an increase in Syn-1 expression in the bowel and maybe even brain which could trigger Alzheimers disease.
99
Q

What is an increase in Astrocytes associated with?

A
  • Increase in asterocytes associated with a disease reactive generating ROS
100
Q

What is an increase in microglia associated with?

A
  • Glial scarring
101
Q

Can the gut microbiota be altered in Schizophrenia and influence behavioural outcomes, and if so, which pathway is it that is being altered?

A
  • YES
  • The differences were found in the microbiome (phyla) and suggests that it has the potential to be influencing some of the outcomes we see in the disorder
  • The glutamate-glutamine-GABA cycle is being altered
102
Q

When the gut microbiome is transplanted from Schizophrenic mice to germ free mice, what occurs?

A
  • There is induced Schizophrenia-relevant behaviours in Germ free recipient mice
103
Q

What did a metagenomic analysis of the microbiota of two different mice populations (one with Schizophrenia and one with normal mice) show?

A
  • Showed that there are differential pathways between Schizophrenic microbiota and normal mice microbiota.
  • Confirming that germ free mice (red LHS) have very different microbiota and when further assessed, it was further confirmed that these were consistent with microbiota that had been transplanted into animals from schizophrenic patients.
104
Q

In BOTH animal models and Schizophrenic patients, are the microbiome and behavioural outcomes affected?

A
  • YES
105
Q

What is acylated ghrelin defined as?

A
  • The natural ligand of growth hormone secretagogue receptor type 1A (GHS-R1A) which is expressed throughout the brain
106
Q

Where is secretagogue receptor type 1a (GHS-R1A) expressed, what is the ligand and what type of mechanism could it be used for?

A
  • These receptors are expressed throughout the brain
  • The ligand is Acylated ghrelin
  • It could be a potential mechanism for controlling a range of other things such as cell integrity
107
Q

Initially, looking at the GI tract and nutrition, Ghrelin was looked at as the ‘increasing hunger’ hormone secreted. However it has a range of other functions, what are these? (8 areas)

A
  1. Anti apoptotic and anti inflammatory effects
  2. Increase in growth hormone (GH), ACTH and Prolactin
  3. Increase in food intake, Adipogenesis and blood glucose levels
  4. Modulation of ovary function (Decrease in GnRH and LH secretion)
  5. Increase in osteoblasts proliferation and bone mineral density
  6. Increase in gastric emptying and intestinal motility, also role in gastroprotection
  7. Vasodilation (Increase in angiogenesis and improves endothelial function)
  8. Increase in inotropism and cardiac output (CO), decrease in afterload
108
Q

Could Ghrelin play a role in neuroprotection, and if so, what did potential studies show for Ghrelin (and via which mechanism) for neuroprotection?

A
  • YES possibly
  • All studies looking at Ghrelin showed that it provided some level of protection PRIMARILY via a decrease in apoptosis (also inflammation but mainly apoptosis)
109
Q

Via which mechanism can Ghrelin inhibit apoptosis?

A
  • Via the Caspase 3 pathway –> it targets Caspase 3 which is the key executioner protein (Acyl-Ghrelin–> Erk, MAPK, PI3K, PKC, PKA–> Akt–> BAX decreasing, BCl2 increasing–> INHIBITION of Cyt- C release hence NO APOPTOSIS
  • Ghrelin can also target neurtrophils and lymphocytes (anti inflammatory role potentially reducing toxins and cytokines)
110
Q

Which cells does Ghrelin inhibit to try and reduce inflammation?

A
  • Neutrophils, Lymphocytes and microglia.
  • This inhibits the cytokines being formed (from neutrophils and microglia) and the neurotoxins from the neuts from being formed
111
Q

What has both endogenous and exogenous Ghrelin been shown to protect in a MPTP-induced mouse model of PD?

A
  • The endogenous and exogenous Ghrelin have been shown to protect dopamine neurons of the SNpc in a MPTP induced mouse model of PD
  • Compared to control, there is a significant decrease in the amount of cells and when Ghrelin is added to the PD model, there is an increase in number of cells. Is NOT a complete reversal BUT IMPROVEMENT COMPARED TO SALINE.
  • With a Ghrelin KO, there are less cells and dopamine being generated
112
Q

In a MPTP-induced mouse model of PD, was Ghrelin shown to stimulate an increase in striatal dopamine release?

A
  • YES
113
Q

Three things that occur during sleep?

A
  1. Growth hormone surge during sleep
  2. Brain plasticity (improvement in the wiring of neurons
  3. Flushing metabolic waste from the brain
114
Q

What is a lack of sleep associated with?

A
  • Lack of sleep is associated with illness and impaired functioning
115
Q

Do animals that are fully deprived of sleep die?

A
  • YES
116
Q

What 4 main things is sleep linked with?

A
  1. Conserving energy
  2. Enhances survival/adaptation.
  3. A learning/memory consolidation.
  4. Restorative/repair of injury. (Brain plasticity-forming skills and memories, and may directly affect recovery processes)
117
Q

What is neuro plasticity defined as?

A

Neuroplasticity is defined as the ability of the nervous system to change its activity in response to intrinsic or extrinsic stimuli by reorganizing its:

  • Structure
  • Functions
  • Connections
118
Q

What part of the structure of a neuron determines how strong its neural network is?

A
  • The dendrites
119
Q

Are there stronger nerve impulses in the brain whilst awake or asleep?

A
  • Stronger nerve impulses whilst awake
120
Q

After a stroke causing infarct damage, will all of the neurons be dead?

A
  • NO

- Some will survive

121
Q

With the neurons that survive after stroke, will they function the same as before, and why/why not? Also if so, what can increase the synapses?

A
  • NO they will NOT
  • This is because they have lost their synapses (connections) with other neurons that are now dead
  • We can try and stimulate the brain plasticity to INCREASE the neurite outgrowth for the surviving neurons to link up with neighboring neurons hence trying to build the connections back up again and communications in the injured areas of the brain
122
Q

If there is infarct damage in a brain and you are trying to promote NEW growth (stem cells), what is an important factor to consider?

A
  • Angiogenesis
  • This is because the cells will have lost cerebral vasculature, O2 and glucose thus a HIGH demand for blood supply.
  • So if you have increased brain plasticity BUT have no gliogenesis or angiogenesis, then you won’t have a good outcome
123
Q

If you are able to stimulate brain plasticity in a damaged brain, however have no gliogenesis or angiogenesis, will there be a good outcome?

A
  • NO
  • This is because his is because the cells will have lost cerebral vasculature, O2 and glucose thus a HIGH demand for blood supply.
  • So if you have increased brain plasticity BUT have no gliogenesis or angiogenesis, then you won’t have a good outcome
124
Q

Which type of the brain level is trying to be stimulated for stroke patients with infarct damage?

A
  • The penumbra
125
Q

What does Gliagenesis cause?

A
  • Increased proliferation and differentiation of astroglial cells hence glial scarring
126
Q

Is sleep neuroprotective in the acute phase of stroke and does it promote neuroplasticity?

A
  • Yes and yes
127
Q

Sleep disorders such as insomnia and sleep didn’t disordered breathing frequent after stroke?

A
  • YES

- They may affect >50% of patients

128
Q

What are 4 possible mechanisms linking insufficient or fragmented sleep?

A
  1. Elevated sympathetic activation.
  2. Intimate hypoxaemia
  3. Oxidative stress (exacerbate neuroinflammation)
  4. Inflammatory changes
129
Q

Sleep disorders may have detrimental effects during the ___ phase of stroke (and the evolution of the ____)

A
  • Sleep disorders may have detrimental effects during the ACUTE phase of stroke (and the evolution of the PENUMBRA)
130
Q

What % of blood flow reduction is enough to trigger a significant amount of infarction/damage in the core of the brain (in context of ischaemic cascade)

A
  • 70% reduction in blood flow is enough to trigger the core infarction
131
Q

What occurs in terms of the biochemistry of the core of the brain when we get an occlusion?

A
  • The collateral blood supply in surrounding tissue (blue green and yellow regions) increase their blood supply to try and compensate for occlusion.
  • The green and yellow region are affected by the diminished blood supply BUT because of the collateral blood supply, there is some reperfusion. That region is known as the ‘penumbra’ that is in a holding phase.
132
Q

What is the Penumbra?

A
  • A region in the brain that can partially reverse ischaemia in the brain by increasing blood supply to compensate for the occlusion
  • This has a collateral blood supply where reperfusion occurs
133
Q

Why are the cells in the Penumbra called the holding phase?

A
  • Because the cells within this region are still alive and functioning but they are in a hibernation phase.
134
Q

If blood supply is NOT restored in the infarction area of the brain over an acute period of time then what will occur? (context of biochem and Penumbra)

A
  • If blood supply is NOT restored over an acute period of time, then eventually it will trigger apoptotic mechanisms and the cells within the region will DIE.
  • So if blood supply is NOT improved in this region over time, then the core will expand and increase in size thus ending up with a much bigger core.
135
Q

What can researchers try and target/stimulate to aim for reperfusion and preservation of neurons following stroke?

A
  • They can try and stimulate mechanisms that can reverse things like apoptosis or things that improve neuronal function to keep that area alive for as long as possible.
136
Q

What is the morphology and the biochemistry of the ischaemic core of the brain in terms of the Icahemic cascade?

A

The core morphology is infarction and the biochemistry is:

  • Ionic failure
  • Anoxic depolarisation
  • A decrease in glucose use
137
Q

What is the morphology and the biochemistry of the Penumbra of the brain in terms of the Icahemic cascade?

A

The Penumbra morphology is inflammation and apoptosis and the biochemistry is:

  • Decrease in protein synthesis
  • Acidosis
  • Increase in in oxygen extraction
  • Selective gene expression (more green and yellow regions–>outermost regions)
138
Q

Does sleep deprivation/disturbances increase cerebral infarct area?

A
  • YES.
139
Q

In a study (Gao et al. 2010) that measured infarct volume with sleep deprivation for 12 hrs versus no sleep deprivation, what were the findings (i.e. which layers of the cortex does the infarct occur, what is the infarct volume like etc)?

A
  • Those that were sleep deprived had a MUCH GREATER infarct volume
  • It occurs in the more latter regions (L5 and L6- hippocampal regions in the cortex associated with the parietal lobe-motor cortex)
  • greater damage in the cortex area means reduced function in the sleep deprived animals
  • If any damage is in the hippocampal region, then that can affect memory
140
Q

In a study (Gao et al. 2010) that measured infarct volume with sleep DISTURBANCE for versus NO SLEEP DISTURBANCE, what were the findings (i.e. which layers of the cortex does the infarct occur, what is the infarct volume like etc)?

A
  • Significant worsening outcome (infarct damage) in L5 and L6
    Means that sleep plays a key role in reducing the AMOUNT of damage following stroke
141
Q

What is GFAP a marker for?

A
  • Astrocytes and this is in the context of stroke and sleep -reactive astrocytes
142
Q

Which two things does healthy sleep following stroke reduce?

A
  1. Reactive astrocytes (GFAP marker for this)

2. Neurocan (this inhibits neurite outgrowth)

143
Q

What have animals subjected to a stroke without sleep deprivation shown in terms of GFAP and Neurocan?

A
  • Most ejected to a stroke without sleep deprivation have reduced GFAP expression (meaning less reactive astrocytes and thus ROS production – reduced to clear scarring).
  • The animals with more sleep means less inhibition on neurite outgrowth by Neurocan
  • The more sleep deprived animals have increased neurocan which may inhibit neurite outgrowth
144
Q

Is neurogenesis increased in stroke mice that have undisturbed sleep?

A
  • YES
145
Q

Compared to sham animals, does cerebral ischaemia show an increased amount of axon sprouting in the stroke animals, and how is synaptogenesis affected (and what does this indicate)?

A
  • YES - meaning that healthy sleep in stroke animals is increased compared to sham
  • Synaptogenesis is INCREASED in those that are not sleep deprived following stroke- this indicates increased axonal sprouting thus improved connections and neuronal signaling
146
Q

Do both animal and human data provide evidence that promotion of sleep (and treatment of sleep disorders) is neuroprotective in the acute phase of stroke and promotes neuroplasticity thus recovery after stroke?

A
  • YES
  • There are multiple facets of sleep intervention on recovery following cerebral ischaemia
  • Could lead to neuroprotection/neuroplasticity/neurogenesis
147
Q

Is there a higher prevalence and severity of sleep alterations in patients with an early onset form of Alzheimer’s disease?

A
  • YES
148
Q

What are 5 changes in sleep architecture and circadian rhythms in people with Alzheimer’s disease?

A
  1. Increased sleep latency and night-time Awakenings.
  2. Decreased slow wave sleep.
  3. Decreased rapid eye movement sleep.
  4. Decreased total sleep time
  5. Increased daytime napping.
    - These will exacerbate the other Alzheimer’s symptoms
149
Q

Which three things are sleep problems associated with that is a worsening evolution of Alzheimer’s disease?

A
  • The development of more severe cognitive and neuropsychiatric symptoms.
  • With a diminished quality of life.
  • A higher caregiver Burden
150
Q

What are 6 commonly prescribed medications that may contribute to insomnia in older dementia patients?

A
  1. Beta blockers
  2. Bronchodilators
  3. Corticosteroids
  4. Gastrointestinal drugs (e.g, H2 blockers and cimetidine).
  5. Cardiovascular drugs
  6. Neurologic drugs (e.g, selegiline).
151
Q

What does sleep intensification following sleep deprivation improve in terms of Ts65Dn (down syndrome model) mice?

A
  • sleep intensification following sleep deprivation improves novel object recognition memory in Ts65Dn mice (down syndrome mice)
152
Q

In the context of the graph on the Ts65Dn mice and object recognition memory and sleep, is sleep deprivation for 4 hrs before more sleep an enhancement or negative outcome?

A
  • It is an ENHANCEMENT because they have been sleep deprived first so they are really tired
153
Q

What is the Ts65Dn mice model and what is it used for?

A
  • It is an animal model of down syndrome
  • Provides unique method to investigate mechanisms related to AD like symptoms in patients with down syndrome
  • This model shows a cholinergic decline and cognitive deterioration
154
Q

Did the novel object recognition test improve in the Ts65Dn mice that had sleep enhancement prior to training?

A
  • YES
155
Q

In reference to Ts65Dn mice (down syndrome model- Alzheimer’s Disease symptoms), there is a significant increase in _________ suggesting that the _____ could improve memory with conditions like Alzheimer’s disease.

A

In reference to Ts65Dn mice (down syndrome model- Alzheimer’s Disease symptoms), there is a significant increase in NOVEL OBJECT RECOGNITION suggesting that the SLEEP ENHANCEMENT could improve memory with conditions like Alzheimer’s disease.

156
Q

Which two biomarkers are the gold standard for AD?

A
  • CSF Abeta and Tau levels (but many bad issues with this approach- painful and not a good read) –> maybe better for familial AD
157
Q

What is a way of looking at the relationship between Alzheimer’s and sleep in terms of biomarkers?

A
  • Analyse the changes that appear in certain oscillatory patterns and their relationship with standard biomarkers.
158
Q

In terms of the link between AD and sleep, what did AD patients demonstrate a slowing of?

A
  • AD patients demonstrated a slowing of the awake and REM sleep occipital EEG (from 9.40 Hz to 6.40 Hz)
  • So patients having changes within their sleep patterns by looking at the EEGs and could be very early onset Alzheimer’s and Dementia
159
Q

In terms of the biomarkers in Alzheimer’s disease, what did studies in healthy elderly adults find?

A
  • They found that both diminished slow wave activity (SWA) and SWA disruption were associated with elevated CSF Abeta
160
Q

What type of disorder is obstructive sleep apnea (OSA) defined as?

A
  • A sleep related breathing disorder characterized by pauses in the airflow (collapsibility in the upper airways- interrupting normal ventilation thus disruption of normal sleep pattern)
  • complications include high blood pressure and right heart failure
161
Q

What are examples of sleep apnea induced complications?

A
  • Memory problems
  • Increased insulin resistance
  • Stroke
  • Cardiac problems (right heart failure)
  • High blood pressure
  • Increased traffic and workplace accidents
  • Death
  • Snoring
  • Depression
  • Hormone disruption
162
Q

What types of neurological conditions mean that a person has an increased risk of developing OSA?

A
  • Stroke
  • PD
  • AD
  • MS
  • ALS
163
Q

What are 5 conditions that are associated with OSA in children?

A
  • high BP
  • Stroke
  • Diabetes
  • Heart disease
  • Neurocognitive symptoms and ADHD in children
164
Q

Can sleep fragmentation as a result of OSA exacerbate the attention disorder that characterises ADHD and if so, what does this highlight the importance of?

A
  • YES
  • Highlights the importance of assessing the prevalence of OSA in the differential diagnosis of children with attention deficits
165
Q

Roughly how many deaths in 2015 was all types of air pollution responsible for?

A
  • About 9 million death (16% of all deaths globally)
166
Q

Roughly what % of strokes MIGHT air pollution cause?

A
  • 30% of all strokes

- thus could be one of the major contributors to the global stroke burden

167
Q

What is the proposed mechanism of action for air pollution causing stroke?

A
  • A direct effect of particulate matter – a mixture of solid particles and liquid droplets found in the air and gases such as ozone and nitrogen dioxide – on the vascular system, causing oxidative stress and inflammation.
168
Q

What do recent epidemiological and animal models suggest that sustained exposure to air pollutants can increase the risk of?

A
  • Suggest an increased risk of dementia with sustained exposure to air pollutants
  • BUT underlying mechanisms are UNCLEAR and there are MANY CONFOUNDING factors (e.g. diet and physical activity) and medical history cannot be excluded
169
Q

Air pollution has a greater impact on _____ compared to the other measures. Which complication will this likely cause?

A
  • Air pollution has a greater impact on atrial fibrillation than the other measures.
  • This will likely cause a stroke to occur because the offbeat rhythm can cause blood to pool in the upper chambers and thus cause a clot to form

BMS3052 (14 decks)

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