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Neurodegenerative diseases > Stroke > Flashcards

Stroke Flashcards

1
Q

what is the 2nd leading cause of death globally (2019)?

A

stroke

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2
Q

the top two leading causes of death globally have what in common?

(2019)

A

Stroke is the 2nd leading cause of death globally (2019)
The 1st being ischemic heart disease

Both have to do with the vascular system and where the body isn’t able to supply oxygen to the body.

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3
Q

what percentage of people who have had a stroke die within 1-3 months?

A

20-33% die within 1-3 months

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4
Q

how many stroke survivors leave hospital with a disability in the uk?

A

two thirds

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5
Q

what is the single largest cause of adult disability?

A

stroke

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6
Q

what is the average hospital stay after stroke (in the UK)?

A

Average stay in hospital 28 days but highly variable (major pressure on NHS)

1 in 5 acute hospital beds are occupied by stroke patients

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7
Q

what percentage of strokes occur in people under 65?

A

25%

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8
Q

what fraction of people will have a stroke in their lifetime?

in england

A

1/6

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9
Q

give 3 examples of acute neurodegenerative diseases

sudden onset, secondary progression

A

traumatic brain injury
stroke
TIA

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10
Q

give 4 examples of chronic neurodegenerative diseases

slow onset, progressive

A

alzheimers disease
parkinsons disease
multiple sclerosis
prion disease

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11
Q

what is the biggest obstacle to emergency treatment?

A

many people dont know they are having a stroke and there can be a long time between stroke and getting to hospital

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12
Q

a stroke is a medical emergency.
what campaign has helped people identify a strok ena dvastly reduced emergency care times?

A

the FAST campaign

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13
Q

what are the principles of the FAST campaign?

A

 Face – the face may have dropped on 1 side, the person may not be able to smile, or their mouth or eye may have drooped.
 Arms – the person may not be able to lift both arms and keep them there because of weakness or numbness in 1 arm.
 Speech – their speech may be slurred or garbled, or the person may not be able to talk at all despite appearing to be awake; they may also have problems understanding what you’re saying to them.
 Time – it’s time to dial 999 immediately if you notice any of these signs or symptoms

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14
Q

symptoms in the FAST test identify most strokes, but occasionally strokes can cause different symptoms. what are the other signs and symptoms that could be exhibited?

A
  • complete paralysis of 1 side of the body
  • sudden loss or blurring of vision
  • being or feeling sick
  • dizziness
  • confusion
  • difficulty understanding what others are saying
  • problems with balance and co-ordination
  • difficulty swallowing (dysphagia)
  • a sudden and very severe headache resulting in a blinding pain unlike anything experienced before
  • loss of consciousness
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15
Q

what is the key identifier of a transient ischemic attack?

A

Symptoms of a stroke that disappear quickly and in less than 24 hours may mean you had a transient ischaemic attack (TIA).
These symptoms should also be treated as a medical emergency to reduce the chances of having another stroke

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16
Q

what are the major types of stroke?

A
  • Ischemic (blood clot, blood flow stops)
  • Haemorrhagic (rupture of blood vessel leading to haemorrhage in intracerebral or subarachnoid space)
  • Intracerebral haemorrhage
  • Subarachnoid haemorrhage

also - Transient ischemia attack (TIA): ischemic events.
- Resolve within 24hrs. No tissue death.

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17
Q

breifly what causes cell death in Haemorrhagic stroke?

A

Extracellular haemoglobin induces cell death, mainly via oxidation and inflammation

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18
Q

what occurs in the brain when someone has a subarachnoid haemorrhage?

A

Blood leaks out into the brain tissue at high pressure
Subarachnoid blood distributes rapidly over the entire brain and penetrates easily into the deeper layers of the cortex within a few hours.
Blood released into the subarachnoid space clots almost immediately and disappears ~3 days via clot lysis, which starts early after SAH.

Extracellular haemoglobin induces cell death, mainly via oxidation and inflammation (Bulters et al, 2018).

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19
Q

what percentage of strokes are a result of subarachnoid haemorrhages?

A

5%

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20
Q

what percentage of strokes are a result of intracerebral haemorrhage?

A

10%

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21
Q

what occurs in the when brain when someone has an intracerebral haemorrhage?

A

a rupture in a blood vessel causes blood to invade brain tissue and begin to fill space inside the brain and go within the intracerebral parenchyma
over a period of days blood cells begin to lyse and haemoglobin comes out
extracellular haemoglobin induces cell death, mainly via oxidation and inflammation

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22
Q

what is Cerebral Venous Sinus Thrombosis (CVST)?

A

Blood clot in the venous sinuses, part of the brain’s blood drainage system.
Symptoms include headache, seizure, nausea, weakened or impaired control of one or both sides of body or of limbs (stroke symptoms), abnormal vision
More common in females than males in a 3:1 ration
More common in obesity and younger people

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23
Q

which type of stroke has the highest incidence of death and disability and presents in much younger people?

A

subarachnoid stroke

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24
Q

what occurs in the brain in cerebral venous sinus thrombosis (CVST)?

A

A clot forms in a venous sinus causing an obstruction of flow. Resulting in enlargement and an increase in pressure in these venous structures. This will then cause pressure on that part of the brain that is being drained by these veins

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25
Q

a stroke affecting the Parietal lobe will have an effect on what functions?
(4)

A
  • reading
  • intelligence
  • sensation
  • language
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26
Q

a stroke affecting the Frontal lobe will have an effect on what functions?
(4)

A
  • movement
  • intelligence
  • behaviour
  • memory
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27
Q

a stroke affecting the Temporal lobe will have an effect on what functions?
(5)

A
  • speech
  • behaviour
  • memory
  • hearing
  • vision
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28
Q

a stroke affecting the Occipital lobe will have an effect on what functions?

A
  • vision
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29
Q

a stroke affecting the cerebellum will have an effect on what functions?

A
  • balance
  • coordination
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30
Q

a stroke affecting the brain stem will have an effect on what functions?
(5)

A
  • breathing
  • blood pressure
  • heartbeat
  • swallowing
  • consciousness
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31
Q

the brain needs to be adequately…

A

…perfused

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32
Q

the brain is a small proportion of the body in weight ________ but it uses up a vast amount of energy ________ and cardiac output ________

A

The brain is a small proportion of body in weight
~2.5% body weight
But it uses up a vast amount of energy (compared to its weight- about 8 times than its fair share)
20% energy
15% cardiac output

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33
Q

the brain is expensive to run in terms of_____

A

ATP (energy)

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34
Q

why does the brain consume so much energy?

A

It has no energy stores so has to consume to make its own
the sodium potassium pump is constantly running in all the brain cells to maintain resting membrane potential

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35
Q

what are the typical symptoms for a stroke that occurs in the middle cerebral artery?

A

arm and facial weakness, speech affected
MCA strokes typically present with the symptoms individuals associate most commonly with strokes, such as unilateral weakness and/or numbness, facial droop, and speech deficits ranging from mild dysarthria and mild aphasia to global aphasia

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36
Q

what arteries are most commonly affected

A

Lenticulostriate arteries

As one of the most critical vascular structures in the human brain, lenticulostriate arteries (LSAs) supplies blood to important subcortical areas, including the caudate nucleus, globus pallidus, putamen, and part of the posterior limb of the internal capsule

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37
Q

what is the most common form of stroke?
what arteries is it caused by?

A

Lenticulostriate arteries affected in - Lacunar stroke (most common form of stroke)

causing Contralateral hemiparesis (weakness on one side of the body)

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38
Q

what is Contralateral hemiparesis?

A

weakness on the opposite side as the injury

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39
Q

what is hemiparesis?

A

weakness on one side of the body

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40
Q

a stroke affecting the brain stem can affect what fibre tracts and nuclei?

A

fibre tracts e.g. spinothalamic tract, nuclei of cranial nerves

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41
Q

what occurs rapidly after a flow disturbance?

A
  • O2 depletion
  • energy failure
  • terminal depolarisation
  • ion homeostasis failure
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42
Q

What occurs secondary to flow disturbance

A
  • excitotoxicity
  • spreading depression like depolarisations
  • disturbance of ion homeostasis
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43
Q

what occurs delayed to (in the days and weeks that follow) flow disturbance?

A
  • inflammation
  • apoptosis
44
Q

what is excitotoxicity?

A

refers to an excessive activation of neuronal amino acid receptors. The specific type of excitotoxicity triggered by the amino acid glutamate is the key mechanism implicated in the mediation of neuronal death in many disorders.

45
Q

what are the current treatments available for Ischemic stroke?

A
  • Thrombolysis (tPa, ‘clot busting’)
  • thromectomy
  • antiplatelets (eg apspirin)
  • anticoagulants
  • antihypertensives
  • statins
  • carotid endarterectomy
46
Q

what are the current treatments available for haemorrhagic stroke?

A
  • surgery - Emergency surgery to remove any blood from the brain, repair burst vessels suaully done using a craniotomy. A section of the skull is removed to allow access, it is replaced once all the damage has been repair and the bleeding stops.
  • surgery for hydrocephalus - treating a complication of haemorrhagic stroke, hydrocephalus can be treated by putting a tube called a shunt into the brain to allow the fluid to drain.
47
Q

what are the indications and contraindications for tPa to be used?

A
  • must be an ischemic stroke (confirmed with a brain scan)
  • must be given within 4.5 hours of onset
  • requires certainty there is not intracranial bleeding
  • age limited 18-79
48
Q

how does tPa work to improve the outcome of stroke?

A

tPA attaches to the fibrin on the clot surface. It activates the fibrin-bound plasminogen. Plasmin is subsequently cleaved from the plasminogen affiliated with the fibrin. The plasmin breaks up the molecules of fibrin, and the clot dissolves

tPA helps to restore blood flow to brain regions affected by a stroke, thereby limiting the risk of damage and functional impairment.

49
Q

although statins and antihypertensions dont treat the current problem how do they help the patient?

A

they are going to try to stop the same problem happening in the future by maintaining blood pressure and health of the vascular system

50
Q

what is a thrombectomy?

A

An emergency procedure that can be used to treat a small number of severe ischemic strokes. It removes blood clots and helps restore blood flow to the brain.

It is only effective at treating ischemic strokes caused by a blood clot in a large artery, the blood clots can be removed by inserting a catheter into an artery often in the groin an d small device is passed through it to remove the clot using the device/suction.

51
Q

why are most people given aspirin after an ischaemic stroke?

A

– as well as a painkiller it is an antiplatelet which reduces the chances of another clot forming

52
Q

why might people be given anticoagulants?

A

Some people (those with history of clots, atrial fibrillsation, deep vein thrombosis) may be offered this to reduce risk of a new blood clot developing in the future. They prevent blood clots by changing the chemical composition of the blood. Examples include Warfarin, apixaban and haparins.

53
Q

breifly how do statins work?

A

Usually advised, statins reduce the level of cholesterol in your blood by blocking a chemical in the liver that produces it.

54
Q

what is Carotid enderterectomy?

A

Some ischaemic strokes are caused by narrowing of an artery in the neck called the carotid artery, which carries blood to the brain. - ie carotid stenosis

(CEA) is a surgical procedure used to reduce the risk of stroke by correcting stenosis (narrowing) in the common carotid artery or internal carotid artery. Endarterectomy is the removal of material on the inside (end(o)-) of an artery.
It involves the surgeon making a cut (incision) in your neck to open up the carotid artery and remove the fatty deposits.

55
Q

what supportive short term treatments will be available to help stroke srvivors manage some of the problems that affect them

A
  • a feeding tube inserted into your stomach through your nose (nasogastric tube) to provide nutrition if you have difficulty swallowing (dysphagia)
  • nutritional supplements if you’re malnourished
  • fluids given directly into a vein (intravenously) if you’re at risk of dehydration
  • oxygen through a nasal tube or face mask if you have low levels of oxygen in your blood
  • compression stockings to prevent blood clots in the legs (DVT)
56
Q

how is the clinical outcome of a stroke measured?

breifly describe what it entails

A

National institute of heart stroke scale (NIHSS)
The bigger the score the worse off they are
15-item neurological examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss.

57
Q

what point is statistically significant for tPa helpfulness?

A

3 hours
(4.5 hours is a generous guideline)

58
Q

what is the number 1 risk factor for stroke?

A

high blood pressure
(hypertension)

59
Q

what is normal blood pressure?

A

120/80
Normal adult blood pressure is defined as a systolic blood pressure of 120 mm Hg and a diastolic blood pressure of 80 mm Hg.

However, the cardiovascular benefits of normal blood pressure extend to lower systolic (105 mm Hg) and lower diastolic blood pressure levels (60 mm Hg).

60
Q

what is hypertension?

A

defined as a systolic blood pressure equal to or above 140 mm Hg and/or diastolic blood pressure equal to or above 90 mm Hg. Normal levels of both systolic and diastolic blood pressure are particularly important for the efficient function of vital organs such as the heart, brain and kidneys and for overall health and wellbeing.

61
Q

modifiable risk factors make up what percentage of cumulative stroke risk?

A

60-80%

62
Q

what are the modifiable risk factors of stroke?

A
  • hypertension
  • elevated total cholesterol level
  • smoking
  • physical inactivity
  • obesity
  • asymtomatic carotid stenosis
  • alcohol consumption (>5 drinks/day)
  • atrial fibrilation
63
Q

what are the non modifiable risk factors for stroke?

A

o Older age
o Race (Hispanic, Black)
o Maternal history of stroke
o Sex (Males)
o Diabetes*

64
Q

how do risk factors increase the propensity for stroke?

A

structure and function of blood vessels
* Artherosclerosis
* Stiffening of arteries
* Narrowing thickening and tortuosity of arterioles and capillaries

interface with circulating blood
* Reduction/alteration of cerebral blow flow (CBF)

65
Q

what is atheroma?

A

Accumulation of intracellular and extracellular lipid in the inner layer of large and medium sized arteries

a plaque made of cholesterol, proteins and other substances and cells (Intrinsic Vascular Wall Cells, Endothelium Smooth Muscle Cells, Macrophages, T Lymphocytes, Mast Cells.) that circulate in your blood.
Atheromas grow over time and may lead to coronary artery disease, peripheral artery disease, heart attack or stroke

66
Q

what is atherosclerosis?

A

Atherosclerosis is where your arteries become narrowed, making it difficult for blood to flow through them. It increases your risk of heart attack and stroke.

Atherosclerosis happens when fatty deposits build up in the arteries, which causes them to narrow

Lifestyle changes, like stopping smoking, eating healthily and exercising regularly, can help stop atherosclerosis getting worse.

67
Q

what is an aneurysm?

A

a bulge in a blood vessel caused by a weakness in the blood vessel wall, usually where it branches.
As blood passes through the weakened blood vessel, the blood pressure causes a small area to bulge outwards like a balloon
can cause stroke if it ruptures

68
Q

how can an artery dissection lead to stroke?

A

for example With a carotid artery dissection, the inner lining of the blood vessel tears. At the site of the tear, blood can clot. If the blood clot breaks loose, it can travel to your brain, block off blood vessels and limit blood flow, resulting in an ischemic stroke.

69
Q

what is dissection of an artery?

A

a dissection is a tear of the inner layer of the wall of an artery. The tear lets blood get in between the layers of the wall and separate them. This causes the artery wall to bulge, and the bulge can slow or stop blood flow through the artery.

70
Q

what stroke triggers have been identified?

A
  • Neck trauma (can lead to dissection of vertebral or carotid arteries)
  • Pregnancy/postpartum
  • Systemic infection
  • Use of drugs
  • Mental stress
71
Q

how can triggers cause stroke?

A

along with risk factors triggers can exacerbate the (vascular) inflammation and activation of the coagulation cascade leading to vascular occulsion and haemodynamic insufficiency

72
Q

what percentage of hospitals in the uk have a rapid referral for stroke?

A

12%

73
Q

what percentage of hospitals in the uk have a rapid referral for stroke?

A

12%

74
Q

what percentage of hospitals have acute stroke units with access to brain scanning within 3 hours?

A

<50%

75
Q

what percentage increase is there that someone who has had a TIA will have a full stroke?

A

20% increase

76
Q

stroke was once considered a disoder of the blood vessels?
what factors and processes are now known to be involved?

A

astrocytes, microglia, oligodendrocyte, neurons, vascular cells (endothelial cells, pericytes and endothelial progenitors), matrix components, immune cells (neurtrophils)

inflammatory infiltrations, angiogenesis and vasculogenesis, glial activation, extracellular matrix remodelling, axonal remodelling and remyelination, synaptic and dendritic plasticity

77
Q

compare the normal aerobic metabolism to the situation that occurs in stroke

A

Normally we have oxygen and glucose being delivered to all the cells of our body where they undergo mitochondrial respiration to production of cellular ATP. Then lots of consumption of ATP by sodium potassium ATPase and lots of other things

In stroke suddenly mitochondrial respiration is removed and cellular ATP is going to be depleted leading to generation and accumulation of reactive oxygen species leading to even more atp usage – leads to intracellular acidification and a lot of malfunction and cellular death
the sodium potassium ATPase stops working leading to loss of ionic gradients and a rise in extracellular glutamate leading to depolarisation

78
Q

what are the mechanisms of neurodegeneration in stroke? how are neurons dying?

A

To be active neurons need to maintain multiple processes which requires a lot of energy. However little energy storage in the brain is absolutely dependent on continuous supply of atp.
* Loss of blood supply means no oxygen or glucose supplied so mitochondrial respiration cannot create cellular ATP which leads to very quick energy depletion. If they can’t get energy then they can’t run sodium potassium ATPase, neurons will subsequently depolarise.
* Depolarisation cause voltage gated calcium channels to open allowing calcium in, this results in glutamate release. This causes calcium to be released from the cell. Glutamate also causes cells to take up more calcium so it is a cycle.
* Cells will try to go into anaerobic metabolism, acidifying the environment around cells. low ph from anaerobic metabolism also triggers calcium release form the cells
* Increased calcium causes activation of proteases that degrade proteins and cause cell death.
* Increased calcium results in cytotoxic oedema, causes cells to swell and explode (cell death), and also puts pressure on blood vessels.
* Calcium also moves into mitochondria causing release of free radicals which result in oxidative damage and cell death.
* Reperfusion of tissue means there is more oxygen leading to aerobic metabolism starting back up which also produces free radicals (reperfusion injury)that cause cell death.
* Reperfusion also causes an inflammatory response which results in cell death (an free radical production), which causes more inflammation, and this goes round in a cycle.
* Once this process gets going it is hard to stop

79
Q

markers of what can be used to determine the approximate ages of cerebrovascular lesions?

A

Inflammatory markers used to determine the approximate age of cerebrovascular lesions

Ischemia evokes a robust inflammatory response (hours  days. Highly stereotyped:

80
Q

what is the ischemic penumbra?

A

an area of reduced perfusion sufficient to cause potentially reversible clinical deficits but insufficient to cause disrupted ionic homeostasis

81
Q

what are the features of the ichemic core?

A
  • irreversibly damaged tissue
  • <20% baseline blood flow levels
  • depleted ATP stores
  • failure energy metabolism
82
Q

what are the features of the ischemic penumbra?

A
  • depressed tissue perfusion
  • basal ATP levels and oxygen metabolism
  • normal ion gradients
  • electrical silence
  • suppressed protein synthesis

perinfract zone

83
Q

how is the diffusion perfusion mismatch measured?

A
  • Diffusion-weighted imaging (DWI) :
    – Detects areas of restricted diffusion of water. Liight-up in acute ischemic stroke
  • Perfusion-weighted imaging (PWI):
    – Detects abnormal blood flow
    compare images from the two techniques and overlay to see the mismatch between the penumbra and ischemic core
84
Q

what three ways can we study stroke?

A
  • Patients (post-mortem, clinical trials)
  • Animal models (eg. Medial Cerebral Artery Occlusion)
  • In vitro studies (eg. Oxygen Glucose Deprivation)
85
Q

what possible stroke treatment options are being explored for the future in the minutes to hours after stroke?

A

acute reperfusion therapies:
intravenous thrombolysis
intra-arterial thrombolysis
combined intravenous/intra-arterial thrombolysis
mechanical reperfusion techniques

86
Q

what possible stroke treatment options are being explored for the future in the minutes to hours to days after stroke?

A
  • neuroprotective therapy: antinecrotic agents, antiadhesion/ antiinflammatory agents, antiapoptopic agents
  • combined thrombolysis and neuroprotective therapy
  • tight control of glucose, perhaps insulin administration
  • tight control of temperature, perhaps antipyretic administration, perhaps hypothermia
87
Q

what possible stroke treatment options are being explored for the future in the days weeks or months after stroke?

A
  • restorative treatments targeting specific deficits (eg gait retraining, arm function)
  • pharmacology couple closely with rehabilitation
  • growth factors coupled with rehabilitation
  • stem cell therapy coupled with rehabilitation
  • gene therapy
88
Q

what was the result/effect when simulated ischemia is combined with glutamate blockers?

A

When add simulation ischemia (no oxygen, no glucose, cyanide) – the neurons start to depolarise bcos they lack membrane potential
While adding these things glutamate receptor blockers are also added – and the effect was that even with simulated ischemia the cells are still happy when the glutamate blockers are there, they show practically no depolarisation and very little (relatively) current change

89
Q

removal of oxygen and glucose and addition of cyanide blocks mitochondrial respiration and causes…

A

Causes sharp increase in glucose receptor activation and anoxic depolarisation

90
Q

what is the standard model of stroke?

A

middle cerebral artery occlusion – clamp on MCA for an amount of time and see what happens

91
Q

imaging ATP luminescence after a MCA occlusion tells us what about reversal of focal ischemia?

A

reversal of focal ischemia after mechanical occlusion of the middle cerebral artery for 1h. Simultaneous imaging of the tissue content of ATP and protein synthesis. Note rapid restoration of energy metabolism, but not protein synthesis. A few hours after restoration of blood flow, energy metabolism secondarily fails in the area which protein synthesis did not recover

When release the clamp the atp is back, 3 hours later you see an area with less atp, 6 hours less ATP and a day later there is no atp in the area
In the core they lose protein synthesis completely, in the penumbra they have a little bit
3 days later they have essentially lost the whole area that had a loss of protein synthesis

92
Q

what are the three types of nitric oxide in the body?

A

eNOS - endothelial
nNOS - neuronal
iNOS – inducible
(macrophages)

93
Q

whats the normal function of nitric oxide in the body?

A

Nitric oxide (NO) affects two key aspects of O2 supply and demand: It regulates vascular tone and blood flow by activating soluble guanylate cyclase (sGC) in the vascular smooth muscle, and it controls mitochondrial O2 consumption by inhibiting cytochrome c oxidase

94
Q

what are the functions of endothelial derived nitric oxide?

A

Endothelium derived nitric oxide has important antiatherogenic properties: enhancement of vasodilatation. inhibition of platelet aggregation (antiaggregant). inhibition of leucocyte migration, antiproliferation, anti cell adhesion

95
Q

what are the roles of neuronal derived Nitric oxide?

A

Specifically, nNO acts in part through regulation of dopamine (DA) release, transporter function, and the elicitation of neuroprotection/neurodegeneration of neurons in conditions such as Parkinson’s disease (PD).

96
Q

what are the roles of inducible nitric oxide?

A

Inducible NOS (iNOS) is silenced in most tissues, but transcriptionally activated by inflammatory cytokines, which lead to increased levels of NO during an inflammatory response and contributing to free radical-mediated tissue injury in inflammatory disorders, including atherosclerotic plaque formation

97
Q

how does NO loss lead to vasoconstriction/ have a negative effect on vascular flow?

A
  • Platelet aggregation
  • Leukocyte adhesion to endothelial cells
  • Smooth muscle proliferation
  • Key steps to vascular inflammation
98
Q

how is NMDA activation coupled with nitric oxide toxicity?

A

NO is produced by neuronal NO synthase (nNOS), an enzyme tethered to the NMDA receptor complex by the postsynaptic density protein-95 (PSD95)

99
Q

what effect can blocking the interaction of PSD-95 with NMDA have on nitric oxide production and stroke?

A

suppressing the expression of the NMDAR scaffolding protein PSD-95 (postsynaptic density-95) selectively attenuated excitotoxicity triggered via NMDARs, but not by other glutamate or calcium ion (Ca2+) channels.
NMDAR function was unaffected, because receptor expression, NMDA currents, and 45Ca2+ loading were unchanged.
Suppressing PSD-95 blocked Ca2+-activated nitric oxide production by NMDARs selectively, without affecting neuronal nitric oxide synthase expression or function.
Thus, PSD-95 is required for efficient coupling of NMDAR activity to nitric oxide toxicity, and imparts specificity to excitotoxic Ca2+ signaling.

100
Q

knockdown of PSD-95 had what effect on simulated stroke?

A

Reduce fraction of dead neurons (following NMDA application) – not completely but reduced the death cost

101
Q

how does the drug NA-1 (Nerinetide) have neuroprotective effects on ischemic stroke?

A

Nerinetide is a neuroprotective eicosapeptide that suppresses the interaction of NMDAR/post-synaptic density protein 95 (PSD-95) to prevent the neurotoxic signaling of nNOS in AIS
Copied the final amino acid of c terminal of nmda to create a peptide that sequesters psd-95 away

102
Q

what is L-NAME?

A

a NOS inhibitor

103
Q

describe the results that were shown in the N1A trial in the primate

A

A study in primate brain, MDA occlusion and applied a placebo or their peptide (N1A or Tat-NR2B9c)
Difference in infarction site - more brain tissue was rescued in the N1A treated primate
Neurobehavioral outcomes were measured throughout the 30-day observation period using the non- human primate stroke scale (NHPSS)
Primate score is lower when they receive the drug

104
Q

how is nitric oxide produced in the body?

A

The body synthesizes nitric oxide from the amino acid L-arginine by means of the enzyme nitric oxide synthase. The main site of the molecule’s synthesis is the inner layer of blood vessels, the endothelium, though the molecule is also produced by other types of cells.

105
Q

give two examples of glutamate receptor blockers

A

MK-801 (NMDAR blocker)
CNQX (AMPAR blocker)

106
Q

give an example of a calcium channel blocker

A

Nimodipine

107
Q

describetthe possible involvement of TRPM2 TRPM7 and NMDAR in ischemic neuronal death

A

Ischemia causes a reduction in extracellular divalent cations (1) which activates TRPM7 channels. Ischemia also causes excitotoxicity, which activates NMDARs (2), contributing to the rise in intracellular calcium (3) and the formation of ROS and RNS (4) and H2O2 (5). These, along with increases in cytoplasmic ADPR (6), feed back onto TRPM2 and TRPM7 channels to further increase their activity (7). This self-sustaining positive feedback loop remains operative even if excitotoxicity becomes inactivated through glutamate receptor inactivation, membrane depolarization or antiexcitotoxic therapy. NOS, nitric oxide synthase. Ca2+-CaM, calcium + calmodulin.

Neurodegenerative diseases (9 decks)

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