Lecture 36: Ischemia Reperfusion

Question 1

What percentage of the brain is used for signaling, and what percentage is used for maintaining cellular activity?

Answer 1

Signaling: 75%

Cellular activity: 25%

Question 2

Are metabolic rates higher in gray or white matter?

Answer 2

Gray matter - neurons

Question 3

Blood brain barrier

Answer 3

Site of entry for energy rich substrates; transporters fo uptake of glucose, monocarboxylic acids

Question 4

What is the preferred energy source of the brain?

Answer 4

Glucose

Question 5

What energy sources can be used secondarily under low glucose conditions?

Answer 5

Glycogen, lactate, ketone bodies

Question 6

Primary neuronal cultures/co-cultures

Answer 6

Neurons taken up from brain; can be excitatory (glutamate) or inhibitory (GABA)

Question 7

Cell lines

Answer 7

Immortalized, can divide due to tumor component

Question 8

Samples of brain

Answer 8

Organelles or brain slice cultures

Question 9

Surgical methods in live animals

Answer 9

Focal ischemia or global ischemia produced

Question 10

In vivo imaging techniques

Answer 10

Humans; PET scans - analogs of glucose fluorescently tagged and observed in brain regions

Question 11

Magnetic Resonance Spectroscopy (MRS)

Answer 11

Utilizes glucose labeled with radioactive isotope and obtain NMR spectra

Question 12

Focal cerebral ischemia

Answer 12

Focal disruption of blood flow to a part of the brain due to occlusion of artery (region supplied by artery is deprived of circulation)

Question 13

Global cerebral ischemia

Answer 13

Transient impairment of blood flow to the whole brain

Question 14

What steps are taken to minimize damage to penumbra during focal ischemia?

Answer 14

Thrombolytic agents injected to minimize damage, during acute phase; necrosis will occur after 3 hours

Question 15

What cells/neurons have the highest vulnerability to injury during global ischemia?

Answer 15

Hippocampal pyramidal cells of CA 1 region, pyramidal neocortical neurons (layers 3,5,6), Purkinje cells and striatal neurons

Question 16

What cells/neurons are most resistant to injury during global ischemia?

Answer 16

CA3 cells in hippocampus, granule cells in dentate gyrus

Question 17

What is the most significant consequence of ischemia injury?

Answer 17

Disruption of ion gradients due to impaired energy metabolism/low ATP

Question 18

The influx of what ion causes overactivation of neurotransmitters and eventually activates cytotoxic pathways?

Answer 18

Ca2+

Question 19

What harmful molecules form as a result of Ca2+ overloading?

Answer 19

Free radicals (NOS/RNS/ROS)

Question 20

What happens to the blood brain barrier following reperfusion injury?

Answer 20

It becomes damaged, leaky; hemorrhage may occur; edema occurs

Question 21

What is the cause of ischemic apoptosis?

Answer 21

Programmed cell death due to deprivation of growth factors, oxidative stress, exposure to inflammatory cytokines, damage to mitochondria

Question 22

What molecules activate caspases to cause apoptosis? What is this pathway called?

Answer 22

FAS ligand and TNF alpha; Extrinsic Pathway

Question 23

What occurs in the intrinsic pathway?

Answer 23

Excess Ca2+ influx disrupts homeostasis, altered calcineurin promotes apoptosis; release of cytochrome c activates caspase-3 to signal apoptosis

Question 24

What are some neuroprotective strategies to treat stroke?

Answer 24

Thrombolytics, NMDA antagonists, GABA agonists, caspase inhibitors, omega-3 fatty acids, heat shock response, antioxidants, growth factors

Question 25

Thrombolytics

Answer 25

Infuse TPA which re-establishes circulation, but some risk of fatal edema or hemorrhage

Question 26

DHA/Omega-3 fatty acid

Answer 26

Beneficial in patients with coronary disease, cancer, rheumatoid arthritis; protective in ischemia; precursor of NPD1 which acts against apoptosis