Repair and Regeneration Flashcards
Where is the boundary between the PNS and CNS?
- right after the connection of the spinal cord
What are Boundary Cap Cells (BCCs)?
- neural crest-derived cells that are present at the entry point for sensory axons or exit point of motor axons —> filters out what comes in and out
- multipotent —> giving rise to several cell types in both PNS and CNS —> forming neurons, glia, smooth muscle cells that can self-renew
- help regulate growth of sensory axons into CNS and prevent motor neurons and central glia exit CNS
In the CNS interface, what are the transition zones comprised of?
Glial limitans (astrocytes endfeet) and Basal Lamina (basement membrane)
What is the role of the Doprsal root in the PNS:CNS Interface?
- Initial projection of fibres can project into CNS but once severed, can regenerate within PNS but fail to enter dorsal root entry zone of CNS
What is the difference of regeneration between the CNS and PNS?
CNS regeneration —> extremely limited; axonal growth fails and glia inhibit axon growth
PNS regeneration —> neurons can sprout collaterals & regenerate; glial cells produce growth factors; macrophages remove debris
What processes happen with PNS Injury occurs?
- if axon is severed = distal ends are cut off from neuronal cell body
- Wallerian degeneration occurs where axon degenerates up to first node closest to injury site —> muscle atrophy causes shrinking due to inactivation
- macrophages phagocytoses dead cells and debris within nerve (myelin unravels)
- Schwann cells de-differentiate and proliferate around distal axon; form bands of Bungner (a bridge), releasing neurotrophic factors that promote axonal regrowth
- not all successful and can cause permanent loss of function
What are some solutions for correcting a PNS Injury?
- regeneration is more successful if the perineurium or epineurium is intact (crunch vs cut) —> Schwann cels can surgical recreate the tubes/connections
- surgical re-apposition (sewing nerve tubes back together)
- neurons do not regenerate equally —> sensory neurons undergo axonal regeneration differently dependent on growth factors they are responsive too
Henry Head:
- severed own radial nerve
- return of pressure and touch by 6 weeks (non-localized)
- 2-6 months later, regained some pain, temperature, and light touch sensation in hand but not all recovered from some proprioception or mechanoreception
What are processes that take place after CNS Injury?
- limited to no regenerative capacity
- distal axon degenerates and demyelinates —> death of oligodendrocytes leading to expansion of injury
- microglia become reactive and phagocytose axon and myelin debris (slower than in PNS)
- astrocytes become more reactive and migrate to injury site —> line up creating physical and chemical barrier around injury site —> boundary of the “glial scar”
What is the most common cause of Spinal Cord Injury in USA?
- Vehicular - 38.3%
- Falls - 31.6%
- Violence - 13.8%
- Sports - 8.2%
- Medical/Surgical - 4.6%
- Other - 3.5%
What is the physiological process that takes place after a CNS Injury?
- reactive astrocytes and microglia release damage-associated molecular patterns (DAMPs), cytokines and chemokines (tracks/migrates immune cells) —> attracting more glial cells to site
- when blood vessels are damaged, causes edema (swelling) in injury site
- Cytokines attract clean up crew (neutrophils and leukocytes) but creates further damage by leaving a cavity
- glial scar limits immune infiltration and creates a physical / chemical barrier to axonal regeneration
What are some inhibitory factors expressed during a CNS Injury?
- glial cells and fibroblasts within glial scar produces chemical barrier for axon growth
- oligodendrocytes express myelin proteins (Nogo-A) inhibiting axon growth when interacting with Nogo receptor 1 and 2
- Astrocytes and fibroblasts —> inhibitory factory’s (CSPGs) interacting with NgRs
- Microglia cells and astrocytes —> immune mediators (interleukins) causing leukocyte (B and T cells) proliferation and activation
