Regeneration and Plasticity Flashcards
Blood-CSF barrier
-increased vascular network and projections of ependymal cells into the ventricle -choroid plexus
-where the CSF is produced
-there are tight junctions to protect CNS that are between the ependymal cells
*no astrocytes
Blood-brain barrier
-astrocytes induce endothelial cells of vessels to create tight junctions to protect CNS from blood borne pathogens
Brain-CSF barrier
-nutrients delivered from CSF to brain
-waste removed from brain to CSF
Lesion
-any damage to any part of the nervous system (PNS or CNS)
-various levels of severity with varying functional deficits
Causes of lesions
-trauma
-ischemia
-space occupying mass (neoplasia, foreign body)
-inflammation
-infection
-degenerative disorders
-congenital defects/structural abnormalities
Signal transmission
-information within the nervous system is transmitted via action potentials
*unidirectional within the axon and tracts/nerves (Soma to axon to terminal branches to post-synaptic cell)
-afferents (sensory) towards CNS, efferents away from CNS
Neuronal injury
-damage to the axon
-damage to the cell body
Damage to the axon
-PNS= regeneration
-CNS= no regeneration
Damage to the cell body
-no regeneration for either PNS or CNS
-will result in cell death and loss of synapse connection
Proximal vs. distal segments
-proximal segment closest to the CNS, distal segment closer to the tissue (muscle)
-if damage to segment occurs, then there is a chance for regeneration. But if cell body dies then no regeneration
Schwann cells
-myelinating cells of the PNS to provide insulation and reorganization of cell membranes to accelerate AP
-will only myelinated one axon per schwann cell
Oligodendrocytes
-myelinate cells in CNS to help with AP
-can myelinate multiple axons from different neurons
Microglia
-diverse roles in nervous system
-embryological origins are still unclear
-balance of resting and activated glia are critical for homeostasis
Wallerian Degeneration
-an active process of axonal degeneration (distal fragment) following injury in PNS or CNS
Steps of Wallerian Degeneration
1.axonal and myelin degeneration
2.neuronal cell body response
3.re-organization and re-growth
Axonal and myelin degeneration
Scwann cells generally don’t die but they do lose connections to the damaged axons
Schwann cells and macrophages phagocytose debris (such as myelin and neurofilaments) resulting in demyelination (takes a few weeks)
-the response from glia is rapid and the macrophages will respond slower (need recruitment via signalling factors that are released from the injured axon/degenerating myeline/inflammation from injury
Microglia play a large role in increased Wallerian degeneration
Microglia’s role in Wallerian degeneration
-secrete factors to promote schwann cell proliferation
-phagocytosis of damaged cells
-secrete growth factors to promote axonal/nerve regeneration
Neuronal cell body response
-after injury, the neuron is not focused on synthesizing neurotransmitters or signal transmission (which is typically its main goal)
-nissl substance is decreased
-changes in nucleus include relaxing chromatin to allow for DNA replication
Re-organization and re-growth during Wallerian degeneration
-degenerating axons and myelin leave a scaffold of endoneurium, which can be used as the pathway to guide regeneration
-schwann cells line-up along the nerve pathway and begin to secrete guidance molecules (Nerve growth factor=NGF)
-damaged axons (proximal segment) sprouts and follows the pathway
Regeneration time length in PNS
-nerves expected to regenerate 1-3 mm/day (2cm/week)
-first axon reaches target in approx. 2 weeks
-staggered regenerative process over the next 10+ weeks (slow)
Unwanted sprouts
-regeneration can produce incorrect or excessive neural connections in response to injury. Motor and sensory axons respond to the same grow signals exhibited by schwann cell.
-can result in pain from connections forming at wrong spot resulting in unwanted feedback
Regeneration in CNS
-typically does not occur
-distal segment degenerates as its no longer connected to the cell body
Why does regeneration not really occur in CNS?
-debris is very slowly cleared away (months) compared to PNS (oligodendrocytes either die or become dormant which means they don’t clear away myelin, and no myelin clearance=no macrophages signalled to aid in myelin clearance)
-oligodendrocytes do not secrete signalling growth factors which means no axonal regeneration (BUT if some schwann cells enter CNS, then some regeneration is possible)
-glial scars form by reactive astrocytes responding to cell injury and inflammation (further inhibits regeneration and re-growth)
Recovery vs. regeneration
-in PNS, regeneration is supported by growth factors released by schwann cells= functional regeneration occurs
-Recovery:
1. may sprout from an adjacent healthy axon to re-innervate the muscle fibers that have lost synapse
2. muscles may hypertrophy to compensate for lost innervation and atrophy
Recovery in CNS
-there is always some recovery after injury
-occurs through synaptic plasticity rather than true regeneration
