regeneration Flashcards
Peripheral nervous system can reinnervate through
peripheral nerve sheaths
In the CNS, there is a modest recovery
what are the Barriers:
- Neuronal death
- Glial cell inhibition of axon growth
- Neural stem cells have limited capacity to -repair.
- Immune responses in the nervous system, mediated by microglia, astrocytes, and oligodendrocytes, release cytokines that further inhibit extensive regrowth
A stroke involving the middle cerebral artery can cause damage to
M1 and both SMA
Mechanisms underlying functional improvement over time may include:
- Unmasked surviving axonal connections
- Signaling changes between surviving neurons
- Modest growth of axon branches, dendrites
- Altered activity in the contralesional (“healthy”) side may assist lesioned side
Altered cortical activity patterns and functional recovery in stroke:
If there is good functional recovery, the altered cortical activity patterns
altered cortical activity patterns DIMINISH – paradoxical
Altered cortical activity patterns and functional recovery in stroke:
If there is poor functional recovery
altered cortical activity patterns remain
Three types of neuronal repair
- Peripheral nerve regeneration – nerve cell bodies intact
- Repair of existing neurons in the CNS -inhibited by glial cell overgrowth due to immune response
- Neuronal replacement in the CNS – rare, and controversial
who was Henry Head
he cut his own nerves (PNS regeneration experiment (1905))
the stages of Regeneration of peripheral nerves:
- Cross section through a peripheral nerve showing the connective tissue sheath of the epineurium and the extracellular matrix–rich perineurium that immediately surrounds the axons and Schwann cells.
- Once the axon is cut, the distal portion degenerates and is phagocytosed by macrophages. After the debris is mostly cleared, the proximal axon stump transforms into a growth cone, and this growth cone interacts with the adjacent Schwann cells.
- Distal to the proximal stump, extracellular matrix components, Schwann cells, immune cells, and connective tissue create a channel or space along which the axon regenerates towards the original target.
Regeneration is more efficient after
crushing versus cutting a nerve.
Molecular and cellular response in peripheral nerve regeneration:
Schwann cells facilitate peripheral axonal regeneration by?
- They express adhesion molecules on their surface
- Secrete axon growth-promoting signals (e.g. BDNF) and neurotrophins
*In parallel, the parent neuron expresses genes that restore it to a growth state.
Three different classes of glia react in the CNS
Glia react strongly to brain insult
- Astrocytes
- Oligodendrocytes
- Microglia
Cellular response to injury in the CNS
- Myelin degeneration
- Production of inhibitory factors by astrocytes, oligodendroglia and microglia
- Inhibitory factors inhibit axon regrowth
- Glial scar forms
Anterior subventricular zone – a stem cell niche
Stem cells become more glia
Close to blood vessels
Transit amplifying cells – neuroblasts
Neurogenesis in humans
- Very limited
- Staying in hippocampus
- Mostly targeting neuron number stability
- Recovery after brain insult seems very limited
- Even addition of neural stem cells in humans seems to have limited effects.
