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Biochemistry > Ischemia > Flashcards

Ischemia Flashcards

1
Q

How does the brain use energy?

A

75% for signaling

25% for essential cellular activity.

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2
Q

Are metabolic rates higher in gray matter or in white matter?

A

gray matter

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3
Q

How do energy-rich substrates enter brain from the blood?

A

Via the blood-brain barrier.

There are transporters for glucose and monocarboxylic acids at the barrier.

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4
Q

What does the brain use as fuel?

A

Glucose, glycogen, lactate, ketone bodies.

Carbohydrate oxidation is the main source of energy in the brain.

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5
Q

Why do excitatory and inhibitory neurons consume equivalent energy?

A

Because they do equivalent work.

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6
Q

Which cerebral vessel has a lower oxygen concentration?

A

cerebral venous blood.

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7
Q

What molecule is made in the astrocytes?

A

glycogen

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8
Q

Glycogen is converted into what molecule that is eventually diffused into neurons?

A

lactate

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9
Q

What metabolic pathways are used in the brain?

A

glycolysis

glycogenolysis

pentose phosphate shunt

malate aspartate shuttle

TCA cycle

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10
Q

What are some experimental models used for the analysis of ischemias?

A

Primary neuronal cultures or co-cultures

cell lines

brain

surgical methods performed in live animals

in vivo imaging techniques

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11
Q

What is a negative of brain imaging?

A

Changes in small structures are not detectable.

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12
Q

What does brain imaging do?

A

Shows metabolic rates of imaging for the whole brain.

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13
Q

What molecule is usd in PET imaging?

A

analogs of glucose. It relies on a metabolite, which enables assays of the hexokinase reaction in all regions of the brain in conscious individuals.

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14
Q

What is magnetic resonance spectroscopy?

A

An imaging method that uses glucose.

It allows assessment of glucose metabolites as they are formed in different pathways.

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15
Q

What is the purpose of magnetic responance spectroscopy?

A

To obtain an NMR that determines the metabolism of precursors via specific neuronal and glial pathways.

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16
Q

True or false: the human brain is inneficient in terms of energy usage.

A

True

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17
Q

What is Magnetic Resonance Spectroscopy (MRS)?

A

Allows for the assessment of glucose metabolites as they are formed in different pathways.

It is used to determine metabolism of precursors via specific neuronal and glial pathways.

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18
Q

What is focal cerebral ischemia?

A

Focal disruption of blood flow to a part of the brain due to occlusion of an artery by an embolus.

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19
Q

What is global cerebral ischemia?

A

Transient impairment of blood flow to the whole brain (e.g. during cardiac arrest).

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20
Q

What type of ischemia accounts for a majority of strokes?

A

focal ischemia

21
Q

How does a focal ischemia occur?

A

When an artery supplying a brain region is occluded by an embolus, thrombus or platelet plug.

22
Q

What is an ischemia core/umbra?

A

The core of neural tissue that is affected by the stroke.

23
Q

What is the penumbra?

A

A rim/area surrounding the umbra.

It is an area of reduced cerebral flow, impaired protein synthesis and preserved energy metabolism.

24
Q

In an acute focal ischemia, what is the focus on?

A

saving the penumbra

25
Q

You enounter a patient who is experiencing a cardiac arrest. Prior to resusciation, they also experience an ischemia. What type of ischemia are they most likely suffering from?

A

global ischemia

26
Q

How does a global ischemia affect neuronal populations?

A

They cause a loss of neuronal populations.

Neurons present within the same vascular position and juxtaposed to each other may be selectively vulnerable or resistant to insult.

27
Q

As blood flow is reduced via an ischemia, how is energy metabolism affected?

A

Energy metabolism is decreased. This causes a reduction in ATP levels and dysfunction of the ion pump.

28
Q

A disruption via ischemia ultimately results in what to cells?

A

apoptosis

29
Q

What is the Pasteur effect?

A

A fall in PO2 leads to enchanced lactate production. This reduces the pH of cells, causing depolarization and the movement of calcium into the cell.

It also causes the release of neurotransmitters.

30
Q

What do NMDA and AMPA/kainate overactivation do?

A

Contribute to excitotoxicity.

31
Q

During excitotoxicity, the loss of ion gradients causes the buildup of what neutrotransmitter in the extracellular space?

A

glutamate

32
Q

During excitotoxicity, the activation of glutamate receptors causes the influx of what ion into the intracellular space?

A

calcium

33
Q

Glutamate receptor activation causes the activation of what pathways?

A

cytotoxic intracellular pathways.

34
Q

What is the function of calpain?

A

It degrates the cytoskeleton.

35
Q

During excitotoxic injury, what is activated?

A

calpain

generation of NO and ROS

Damage to mitocondria

Phospholipase A2

36
Q

You treat a stroke patient wih NR2B intravenously. How does NR2B prevent cell death?

A

It binds to the NMDA receptor, preventing the binding of death-associated protein kinase 1.

37
Q

How to reactive oxygen species affect the membrane?

A

They react with proteins, lipids and DNA, causing structural and function changes in biomolecules.

38
Q

How do reactive oxygen species cause cellular dysfunction and eventual cell death?

A

By reacting with proteins, lipids and DNA found in the neuronal membrane.

39
Q

What barrier is dapaged in the brain during an ischemia?

A

blood brain barrier

The adhesion of leukocytes in this region cause vessel plugging.

40
Q

What is one cause of ischemic apoptosis?

A

exposure to inflammatory cytokines

Damage to mitochondria

oxidative stress

deprivation of growth factor support

41
Q

What does the activation of death receptor Fas promote?

A

formation of DISC, then procaspase-8, then caspases-8 and -3, which eventually activates tBID, which translocates to the mitocondria to execute apoptosis.

This is the intrinsic pathway.

42
Q

The altered activity of protein phosphatase causes translocation of what?

A

BAD

It promotes the mitochondrial apoptotic pathway.

43
Q

In the intrinsic pathway, a loss of calcium from the ER causes activation of what three factors?

A

caspase 3, 9 and 12

44
Q

What organelles does the intrinsic pathway affect?

A

mitocondria and ER

45
Q

What do caspases do?

A

Cleave key structural components of the cytoskeleton and nucleus, a characteristic feature of apoptosis.

46
Q

What is infused into the tissue during thrombolysis/embolectomy?

A

Tissue Plasmogen Activator (TPA).

Reperfusion reestablishes circulation but with risk, may cayse fatal edema or intracranial hemoorhage.

47
Q

What is DHA?

A

On omega 3 fatty acid involved in brain and retinal development.

It has been used in patients with ischemia and spinal cord injury.

48
Q

What does NPD1 act against?

A

apoptosis.

It also promotes cell survival and inhibits brain ischemia.

Biochemistry (13 decks)

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