Lecture 27; Ischemia Brain Injury 4 Flashcards

1
Q

What to we gain a lot of information from?

A

Knowing WHEN cells depolarise

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2
Q

What does knowing when cells depolarise tell us?

A

ECF [Na]/[K] (differential = RMP)
DC potential of single cells
DC potential of the tissue
No depolarisation = no death

Tissue Impedance (how its measured) (continuous picture)
Apparent diffusion coefficient of water

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3
Q

What is the RMP?

A

Cells maintain a negative RMP

Na/K ATPase pumps 3 Na+to 2 K+

Thus the cell: Low Na, high K, -70 mV potential vs outside

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4
Q

What happens to this Na/K ion distribution during ischemia?

A
  • Decreasing BF = increasing Na/K ratio
    i. e Na in, K out

Also water fluxes into the cell as gradient is lost, thus decreased ECF volume. Volume halves suddenly at 30ml/100g/min

This is shown in a stroke model, going penumbra to core

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5
Q

What happens to polarity during ischemia?

A

Cell depolarises to +30mV and remains there as no ATP to restore gradient

Normally would be dynamic rapid depolarisation and repolarisation

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6
Q

How else could we measure depolarisation?

A

Could measure change from resting ECF potential…Electrode in ECF Baseline =0

‘single cell = anoxic depolarisation’

Group of cells = electrode in ECF, ECF becomes relatively negative in ischemic conditions (DC potential)

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7
Q

What does a probe in the ECF really measure?

A

Tissue depolarization measured by DC potential is proportional to~

  • the number of depolarized cells
  • the mean change in membrane potential of cells

Remember: it is a bulk tissue measure, not single cells!

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8
Q

What was shown to occur in AFTER global ischemia of cats in terms DC potential?

A
  • Even after 2hrs not all cells are repolarised
  • Both grey and white matter depolarised (DC potential developed)

Summery;
Sudden decrease in DC potential after start of ischemia indicates that most cells in the region started to depolarize “BULK depolarisation”

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9
Q

What was shown to occur in AFTER global ischemia of cats in terms Ca levels?

A
  • Ca 10000x gradient ECF:ICF normally
  • Ca influx into cells during ischemia only occured in the grey matter! (synaptic opening), but in WM ECF Ca increased was water was flowing into cells

However Ca levels return to normal rapidly even though some cells take hours to repolarise

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10
Q

What happened when an AC current was passed through the brain?

A

Passing an alternating current through the brain

Resistance to AC = Impedance

5Khz = through ECF (Around cells), higher then goes through cells too

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11
Q

What did measuring impedance of 10min carotid artery occlusion in sheep show?

A

Completely resolved within 100mins (cell potential)

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12
Q

What did measuring impedance of 40min carotid artery occlusion in sheep show?

A

Did not resolve even after 100mins.

  • Reperfusion isnt enough to restore cell polarity / ECF volume thats being measured by impedance b/c:
  • Takes time for ATPase to fire up
  • Microcirculation = reduced blood flow b/c pressure of cell swelling there takes time to restore these things
  • Repolarisation takes 30mins to make an impact event if it isnt fully restored at 100mins
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13
Q

What is impedence proportional to?

A

Impedance is inversely proportional to ECF volume!

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14
Q

What are the pros and cons of impedence measurements?

A

Pros;

Continuous vs time

Fine discrimination of timing and pattern

Greater reflection of ECF volume in severe insults

Cons;

Need to know baseline (relative measure)

no regional data

Mostly: relative change

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15
Q

What does the ECF DC potential measure?

A

ECF DC potential~ number of depolarized cells the membrane potential of each cell

This is a bulk tissue measure!

i.e. sudden DC potential after start of ischemia indicates that most cells in the region started to depolarize

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16
Q

What can NMR tell us?

A

Regional brain metabolism

17
Q

What are the causes of profound fetal asphyxia?

A

Placental abruption (massive blood loss too-hypovolemia)

Umbilical cord occlusion

18
Q

What is found in a 14hr baby following profound fetal asphyxia?

A

Loss of NAA (N acetyl Aspartate), High Lactate

Lots of anaerobic respiration occuring despite long after restoration of oxygen

19
Q

What causes the baby 14hr after profound insult to still be producing ATP anaerobically?

A

Mitochondria deteriorate after a significant birth insult as shown by the loss of high energy Pis.

20
Q

Why is the measurement of NAA and lactate useful?

A

Useful for prognosis of long term adverse outcomes.

  • Highly specific
  • Reasonable specificity
21
Q

What would you use to measure regional data?

A

dMRI

22
Q

What does dMRI tell us?

A

3D diffusion probability density function in a voxel that contains spherical cells vs diffusing in tubular structures

i.e WMT constrains brownian motion
GM = diffuse movement

23
Q

How do we map fibre tracks?

A

fractional anisotropy + direction of diffusion

24
Q

What would reduce water diffusion?

A

Reduction in water volume i.e cell swelling…

Piglets showed that over time diffusion decreased after reperfusion and insult….

Delayed cell swelling
- decrease ADC =increase swelling.

i. e cells dont swell till hours after inury (secondary energy failure)
i. e opportunity to prevent further cell death

25
Q

Where has the ECF volume gone when ADC drops?

A

ECF has gone somewhere

  • Evolution of injury
  • Regional spread of secondary energy failure and cell depolarisation despite restoration of blood flow
26
Q

What happens when we compare The acute fall in ADC vs caspase-3 activation?

A

Loss of cell volume = increase caspase 3 activation (cell death commitment)