Neuron Death

Question 1

Neurons are highly dependent on?

Answer 1

Glucose + O2 - diffuse from capillaries, need a constant supply
Stable microenvironment - BBB and supporting glial cells maintain this

Question 2

Which CNS cells store glycogen?

Answer 2

Astrocytes - only have a small supply though, can be converted to glucose for use by neurons

Question 3

Which areas of the “vascular tree” are more susceptible to damage?

Answer 3

Those farther along (more distal to the heart)
When the brain is deprived of O2, autoregulation dilates the arteries - improves local blood flow but “steals” from more distal regions

Question 4

Most common cause of arterial occlusion

Answer 4

Atherosclerosis

Question 5

Which areas of vasculature are most problematic for clot formation?

Answer 5

Areas where branching occurs - causes turbulent flow, more susceptible to damage + plaque/thrombus formation

Question 6

Border-zone (watershed) infarct

Answer 6

Occurs in the regions of the brain located at the junction between two major arterial territories.
These regions are the most vulnerable to ischemia because they are farthest from direct arterial supply

Question 7

Selective neuron death vs infarct

Answer 7

Selective neuron death: death of neurons while surrounding glial cells and blood vessels remain intact (occurs when neurons are more vulnerable than other cells)
Infarct: severe insult, all cell types destroyed

Question 8

Penumbra

Answer 8

Area of brain tissue around the core infarct that is ischemic but still viable for a limited time.
*This is the area where medical intervention in the early stages of a stroke can be beneficial

Question 9

What happens to dead neurons after selective neuron death?

Answer 9

<6hrs to 1 week: neuron undergoes apoptosis or necrosis (cytoplasm becomes eosinophilic, and the nucleus condenses - pyknosis)
1-3 weeks: Microglia surround and consume the dead neuron

Question 10

What happens to dead neurons after infarct?

Answer 10

Dead cells are removed by macrophages that come to the site (since the microglia in the local area are destroyed)

Question 11

Signs of old infarcts

Answer 11

Old/healed infarcts are characterized by cavities, surrounded by reactive astrocytes that bridge the cavities

Question 12

Effects of small vessel occlusion

Answer 12

Can cause thousands of microinfarcts

Question 13

Superior sagittal sinus obstruction

Answer 13

Venous obstruction - prevents outflow of blood, causes hemorrhagic infarction in non-arterial distribution
*Remember the superior sagittal sinus runs down the middle of the skull

Question 14

Hemorrhagic conversion

Answer 14

Occurs when an ischemic stroke turns partially hemorrhagic due to leakage or rupture of damaged vessels in the infarcted area (usually 1-3 days later)

Question 15

Most common site of intracerebral hemorrhage

Answer 15

Basal ganglia

Question 16

Chemical effect of hemorrhage on the brain

Answer 16

Plasma enzymes (especially thrombin) and blood breakdown products are toxic to brain cells

Question 17

Mechanisms of secondary ischemia due to hemorrhage (3)

Answer 17

-Blood collection can distort/compress adjacent tissue
-Blood can cause spasm of adjacent vessels
-Blood may not be able to flow beyond the damaged vessel (more distal damage)

Question 18

Common vascular complications of premature birth (<32 weeks)

Answer 18

Hemorrhagic or ischemic damage in the deep brain tissue
-Small vessels can easily be ruptured by mechanical distortion during birth
-Very premature (<28-30 weeks) - lungs are immature so O2 delivery is suboptimal

Question 19

Germinal matrix

Answer 19

Located next to the lateral ventricles, generates brain cells till ~34 weeks gestation
*Vulnerable to hemorrhage as tissue is fragile and the area is highly vascularized

Question 20

Periventricular leukomalacia

Answer 20

The pre-oligodendrocytes (26-32 weeks) and axons in the white matter surrounding the ventricles are very susceptible to ischemia/hypoxia - this can cause necrosis in the region

*Remember, oligodendrocytes are the myelin-producing cells

Question 21

Concussion

Answer 21

Transient disruption of brain function following acceleration of the head

Question 22

Contusion

Answer 22

Injury to a tissue that causes damage to cells and small blood vessels but no break in the surface (bruise)

Question 23

Mechanism of traumatic head injuries

Answer 23

When the head suddenly hits or is hit by something, the skull stops abruptly but the brain, suspended in CSF, continues moving due to inertia.
This causes the brain to collide with the skull (primary lesion - coup) then rebound to the opposite side (secondary lesion - contrecoup)

Question 24

Distortional brain injury

Answer 24

Occurs when the brain is twisted or rotated within the skull, causing stretching and shearing of axons and small blood vessels rather than a direct blow or impact

Question 25

Why are infants more susceptible to brain injury?

Answer 25

-Softer brain -Open skull sutures -Head is relatively large compared to the body and weak neck musculature

Question 26

**Vasogenic edema** vs **cytotoxic edema**

Answer 26

**Vasogenic:** due to disruption of the BBB - plasma proteins leak into the extracellular space and water follows **Cytotoxic:** due to cellular injury and failure of ion pumps - water accumulation in neurons, glia, and endothelial cells

Question 27

Effects of brain edema

Answer 27

-Dysfunction of neurons due to altered extracellular environment -Decrease in cerebral blood flow due to swelling in the brain -Herniation of brain structures (if severe)

Question 28

Excitotoxicity

Answer 28

Hypoxic neurons release excitatory NTs (like glutamate), causing excessive stimulation in adjacent neurons - results in their damage or death

Question 29

Mechanism of excitotoxicity

Answer 29

Excitatory NTs (glutamate + glycine) bind to NMDA and AMPA receptors, allowing high levels of Ca2+ to enter the neuron

Question 30

Chemical toxins that mimic hypoxia/ischemia

Answer 30

-**CO:** binds to Hb and interferes with O2 delivery -**Cyanide:** interferes with mito activity (binds cyt c oxidase) -**Domoic acic** (shellfish + algae) + **BOAA:** glutamate agonists

Question 31

Post-mortem findings of CO poisoning

Answer 31

-Bright red colour of tissues (because it binds to cytochromes) -Necrosis of the globus pallidus

Question 32

Aging of the NS

Answer 32

Gradual loss of neurons + atrophy - often becomes apparent in the 7th decade of life

Question 33

How abnormal proteins can lead to NS degeneration

Answer 33

Abnormal proteins can accumulate in neurons, causing them to be lost gradually Ex: Alzheimer's disease (beta-amyloid accumulates around neurons and in arteries - causes abnormal phosphorylation of tau protein, which accumulates in neurons)

Question 34

Glymphatic channels

Answer 34

Where metabolic waste products are washed out of the brain in perivascular fluid *In Alzheimer's, the less soluble beta-amyloid plaques can't be cleared in the perivascular drainage

Question 35

Chronic traumatic encephalopathy

Answer 35

A neurodegenerative disease that occurs in the context of multiple mild head injuries (common in contact sports)