Dvpt, Injury, Regen. & Lesions

Question 0

neurulation

Answer 0

conversion of ectoderm to neural plate –> groove –> tube.
starts at cervical level, moves caudally.
* rostral brain = closed at 24 days!

Question 1

major steps of neural development (6 steps)

Answer 1

2 wk: implantation and gastrulation of embryo
3-4 wk: neuronal induction, pattern formation, neurulation
4wk-2 yrs: gliogenesis and myelination
6-16 wk: neurogenesis
12-24 wk: neuronal migration
whole life (esp. 1st year): form and prune neuronal connections

Question 2

neural crest derivatives

Answer 2

1. DRG sensory neurons
2. enteric neurons
3. autonomic neurons
4. schwann cells

Question 3

signal molecs for neurulation/patterning

Answer 3

BMPs: epidermis, roof plate (of neural tube)
SHH: notochord, floor plate (of neural groove/tube)

Question 4

Dorsal-Ventral axis formation

Answer 4

alar plate = dorsal (sensory neurons),
basal plate = ventral (motor neurons).
- separated by sulcus limitans.

Question 5

radial migration

Answer 5

migration of glial cells “upwards” toward pia mater.

Question 6

tangential migration

Answer 6

migration of glial cells perpendicular to radial glia (“horizontally,” parallel to plane of pia mater)

Question 7

gliogenesis steps

Answer 7

1. radial glial cell
   a) radial glial cell
   b) Intermediate Progenitor cell (“IPC”)
   
   • —> neurons, astrocytes and oligodendrocytes.
     
     • neurogenesis ends before gliogenesis ends*

Question 8

myelomeningocele

Answer 8

severe form of spina bifida,
neural tube fails to close at lumbar region –> portion of spinal cord = external on back.
can include Arnold-Chiari malformation
prevent 50% w/ prenatal folic acid.

Question 9

Arnold-Chiari Malformation (“ACM”)

Answer 9

downward displacement of vermis, cerebellum and tonsils.

• -> hydrocephalus and brainstem dysfunction.
• often accompanies myelomeningoceles.

Question 10

occult spinal bifida dysraphism

Answer 10

distortion of spinal cord or roots,

minor symptoms

Question 11

spina bifida occulta

Answer 11

least severe form of spina bifida,
defective vertebral arches, but no change to spinal cord.
–> asymptomatic.

Question 12

anencephaly

Answer 12

failure of rostral end of neural tube to close

–> very small brain, fatal.

Question 13

Holoprosencephaly

Answer 13

Mal-patterned forebrain, common but high fatality in womb.

• alobar: no lobe separation
• semilobar - lobar
• from faulty SHH &/or BMP signaling*
• -> cleft palate, cyclopia

Question 14

microencephaly

Answer 14

impaired IPC proliferation (cortical malformation),

–> small brain, increased risk epilepsy

Question 15

Tuberous Sclerosis Complex (“TSC”)

Answer 15

overproliferation of IPCs (cortical malformation),

–> epilepsy, mental retardation, autism

Question 16

Heterotopia

Answer 16

displaced gray matter deeper into brain
- band or nodule shape
only excitatory signals (no IPSPs) –> epilepsy
(cortical malformation due to defective neuronal migration)

Question 17

Lissencephaly

Answer 17

lack of cortical folding (“smooth brain”)
–> epilepsy
(cortical malformation due to defective neuronal migration)

Question 18

biological steps in reaction to spinal cord injury

Answer 18

1. ion leakage from transection, loss of distal f(x)
2. re-seal axon ends
3. fragment distal stump and degrade myelin
4. remove axon remnants (by microglia, macrophages, schwanns)
5. chromatolysis (soma swells, may die), target tissue atrophy

Question 19

retrograde effects of spinal cord transection

Answer 19

interrupted retrograde transport proximal to damage,

• -> trophic signals lost
• —> synapse retraction

Question 20

anterograde effects of spinal cord transection

Answer 20

aka: “Wallerian Degeneration” (distal to damage)
- axon degradation and remnant removal
- retraction of synapses by damaged neuron
** requires active signaling**
Can have protein mutations that alter rate of degeneration!

Question 21

purpose of Schwann cells in PNS regeneration

Answer 21

Schwann cells surrounding damage re-differentiate,
and produce trophic factors to
a) stimulate axon growth
b) recruit macrophages (to remove remnants)

Question 22

gene modulation for PNS regeneration

Answer 22

after PNS damage, gene modulation occurs to:

a) increase growth genes (GAP43, b-tubulin, cAMP)
b) decrease synapse sensitivity

Question 23

PNS regrowth “Conditioning”

Answer 23

better regrowth if increased GAP43 at site,

so previous damage distally or infusion of GAP43 can improve regrowth.

Question 24

positive aspects for PNS regrowth

Answer 24

1. Schwann cells re-differentiate & produce trophic factors
2. Gene expression changes to promote growth
3. Schwann cells grow to fill in cavity left by damage

Question 25

negative aspects of PNS regrowth

Answer 25

lack guidance cues for regrowth
–> imperfect restoration of:
strength, dexterity, sensory discrimination, conduction speed (80%)

Question 26

Regrowth of neurons in CNS

Answer 26

= very limited (only active regeneration in hippocampus and olfactory bulbs).

bc:
1. inhibitory molecs (Nogo, MAG, CSPG from glial scar)
2. slow myelin clearance

Question 27

axon regeneration inhibitors in CNS

Answer 27

1. signal molecs: Nogo-A, p75NTR, MAG (myelin-assoc. glycoprotein)
2. glial scar creates thick matrix w/ CSPG (chondroitin sulfate proteoglycan) = barrier to growth.

Question 28

why slow clearance of myelin/damage remnants:

Answer 28

1. oligodendrocytes = slow at clearing myelin,

2. Blood-Brain Barrier limits macrophage access to damaged area

Question 29

How improve CNS regrowth?

Answer 29

1. increase neurotrophins (growth signals from target tissue/muscle)
2. transplant stem cells (can grow & differentiate)
3. use neutralizing Abs against Nogo/MAG
4. use chondroitinase (to weaken CSPG barrier)

Question 30

Occam’s razor

Answer 30

theory for diagnosis,
“the simplest explanation (with least # parts) is most likely the right answer”
–> look for one location of lesion that explains as many Sx as possible.

Question 31

Lesion to hippocampus

Answer 31

–> anterograde amnesia.
No consolidation of declarative memories, (normal retrieval)
BUT normal procedural memory.

Question 32

Korsakoff psychosis

Answer 32

lesions to mammillary bodies and medial-dorsal thalamus.
(usually from chronic alcoholism)
- loss of declarative memory retrieval,
(but normal IQ) * confabulatory amnesia*

Question 33

problems (only) with memory retrieval

Answer 33

= lesion to cerebral cortex (~retrograde amnesia)

ie: Alzheimer’s, traumatic injury, etc.

Question 34

Urbach-Wiethe disease

Answer 34

a lipid proteinosis, causes bilateral mineralization of the amygdala

• hypersexual
• decreased fear response, miss social emotion cues
  (ie: don’t look at ppl’s eyes when talking, instead at mouth)
• loss of memories w/ emotional content

Question 35

Brown-Sequard Syndrome

Answer 35

= hemisection of the spinal cord.
Cuts:
1. Dorsal column (STT) –> Contralateral pain and temp sense loss
2. Lateral funiculus (CST) –> IPsilateral Upper motor neuron loss

Question 36

Upper motor neuron syndrome

Answer 36

“Up, up, up!”

1. decreased strength (always w/ motor neuron damage)
2. increased tone
3. hyperreflexia
   * 4. Up-going (positive) Babinski sign

Question 37

Lower motor neuron syndrome

Answer 37

1. decreased strength (always w/ motor nn. damage)
2. decreased tone
3. hypOtonia
   * 4. Muscle wasting and fasciculations

Question 38

Anterior Spinal Artery syndrome

Answer 38

= occlusion of Ant. Spinal artery (ie: trauma/knife cut, tumor, etc.)
often emboli form at L4 or T1
loss of function, BILATERALLY in:
1. CST –> Upper motor nn syndrome (& loss of motor function)
2. STT –> loss of pain/temp sense
** dorsal column (touch) spared! **

Question 39

Millard Gubler syndrome

Answer 39

= occlusion of paramedian branch of basilar artery (in pons)

• -> damage to:
  1. pyramidal fascicles –> Contralateral upper motor nn syndrome
  2. (some) of CN VI tract –> CN VI palsy = diplopia, no abduction