Dvpt, Injury, Regen. & Lesions Flashcards
neurulation
conversion of ectoderm to neural plate –> groove –> tube.
starts at cervical level, moves caudally.
* rostral brain = closed at 24 days!
major steps of neural development (6 steps)
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
neural crest derivatives
- DRG sensory neurons
- enteric neurons
- autonomic neurons
- schwann cells
signal molecs for neurulation/patterning
BMPs: epidermis, roof plate (of neural tube)
SHH: notochord, floor plate (of neural groove/tube)
Dorsal-Ventral axis formation
alar plate = dorsal (sensory neurons),
basal plate = ventral (motor neurons).
- separated by sulcus limitans.
radial migration
migration of glial cells “upwards” toward pia mater.
tangential migration
migration of glial cells perpendicular to radial glia (“horizontally,” parallel to plane of pia mater)
gliogenesis steps
- radial glial cell
a) radial glial cell
b) Intermediate Progenitor cell (“IPC”)- —> neurons, astrocytes and oligodendrocytes.
- neurogenesis ends before gliogenesis ends*
- —> neurons, astrocytes and oligodendrocytes.
myelomeningocele
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.
Arnold-Chiari Malformation (“ACM”)
downward displacement of vermis, cerebellum and tonsils.
- -> hydrocephalus and brainstem dysfunction.
- often accompanies myelomeningoceles.
occult spinal bifida dysraphism
distortion of spinal cord or roots,
minor symptoms
spina bifida occulta
least severe form of spina bifida,
defective vertebral arches, but no change to spinal cord.
–> asymptomatic.
anencephaly
failure of rostral end of neural tube to close
–> very small brain, fatal.
Holoprosencephaly
Mal-patterned forebrain, common but high fatality in womb.
- alobar: no lobe separation
- semilobar - lobar
- from faulty SHH &/or BMP signaling*
- -> cleft palate, cyclopia
microencephaly
impaired IPC proliferation (cortical malformation),
–> small brain, increased risk epilepsy
Tuberous Sclerosis Complex (“TSC”)
overproliferation of IPCs (cortical malformation),
–> epilepsy, mental retardation, autism
Heterotopia
displaced gray matter deeper into brain
- band or nodule shape
only excitatory signals (no IPSPs) –> epilepsy
(cortical malformation due to defective neuronal migration)
Lissencephaly
lack of cortical folding (“smooth brain”)
–> epilepsy
(cortical malformation due to defective neuronal migration)
biological steps in reaction to spinal cord injury
- ion leakage from transection, loss of distal f(x)
- re-seal axon ends
- fragment distal stump and degrade myelin
- remove axon remnants (by microglia, macrophages, schwanns)
- chromatolysis (soma swells, may die), target tissue atrophy
retrograde effects of spinal cord transection
interrupted retrograde transport proximal to damage,
- -> trophic signals lost
- —> synapse retraction
anterograde effects of spinal cord transection
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!
purpose of Schwann cells in PNS regeneration
Schwann cells surrounding damage re-differentiate,
and produce trophic factors to
a) stimulate axon growth
b) recruit macrophages (to remove remnants)
gene modulation for PNS regeneration
after PNS damage, gene modulation occurs to:
a) increase growth genes (GAP43, b-tubulin, cAMP)
b) decrease synapse sensitivity
PNS regrowth “Conditioning”
better regrowth if increased GAP43 at site,
so previous damage distally or infusion of GAP43 can improve regrowth.
positive aspects for PNS regrowth
- Schwann cells re-differentiate & produce trophic factors
- Gene expression changes to promote growth
- Schwann cells grow to fill in cavity left by damage
negative aspects of PNS regrowth
lack guidance cues for regrowth
–> imperfect restoration of:
strength, dexterity, sensory discrimination, conduction speed (80%)
Regrowth of neurons in CNS
= very limited (only active regeneration in hippocampus and olfactory bulbs).
bc:
1. inhibitory molecs (Nogo, MAG, CSPG from glial scar)
2. slow myelin clearance
axon regeneration inhibitors in CNS
- signal molecs: Nogo-A, p75NTR, MAG (myelin-assoc. glycoprotein)
- glial scar creates thick matrix w/ CSPG (chondroitin sulfate proteoglycan) = barrier to growth.
why slow clearance of myelin/damage remnants:
- oligodendrocytes = slow at clearing myelin,
2. Blood-Brain Barrier limits macrophage access to damaged area
How improve CNS regrowth?
- increase neurotrophins (growth signals from target tissue/muscle)
- transplant stem cells (can grow & differentiate)
- use neutralizing Abs against Nogo/MAG
- use chondroitinase (to weaken CSPG barrier)
Occam’s razor
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.
Lesion to hippocampus
–> anterograde amnesia.
No consolidation of declarative memories, (normal retrieval)
BUT normal procedural memory.
Korsakoff psychosis
lesions to mammillary bodies and medial-dorsal thalamus.
(usually from chronic alcoholism)
- loss of declarative memory retrieval,
(but normal IQ) * confabulatory amnesia*
problems (only) with memory retrieval
= lesion to cerebral cortex (~retrograde amnesia)
ie: Alzheimer’s, traumatic injury, etc.
Urbach-Wiethe disease
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
Brown-Sequard Syndrome
= 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
Upper motor neuron syndrome
“Up, up, up!”
- decreased strength (always w/ motor neuron damage)
- increased tone
- hyperreflexia
* 4. Up-going (positive) Babinski sign
Lower motor neuron syndrome
- decreased strength (always w/ motor nn. damage)
- decreased tone
- hypOtonia
* 4. Muscle wasting and fasciculations
Anterior Spinal Artery syndrome
= 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! **
Millard Gubler syndrome
= 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
