Neuronal degeneration and reg Flashcards
Damage at the Dendrite or synapses usually causes?
Loss of dendrites or synapses can usually be resorted by regrowth/plasticity
Damage at the cell body usually causes?
Cell death and due to the fact that mature neurons are post-mitotic it is no replaced
Damage to an Axon or target innervation causes?
In the CNS axon regrowth is inhibited/limited by the environment; in the PNS axonal regrowth is possible but it needs support/guidance cues
How does Axonal injury elicit a regenerative response I the neuron soma?
Loss of normal retrograde neurotropic signals; Retrograde axonal transport of positive (growth) signals from nerve stump
in Wallerian degeneration what is the distal and proximal end? What happens to the distal end? What happens to the proximal end?
the distal end is the end that has been severed from the cell body it degrades all the way to the site of innervation; the proximal end is the side with the cell body and it degrades to the next node of ranvea
in Wallerian degeneration what three things happen to re-establish normal neuronal function?
Regeneration of the proximal axon involves; Axon guidance path and molecular cues; re-myelination by the glial cells; re-innervation of target tissue
In axonal transport what supports the movement? Synthesis and assembly of molecules occurs in the? What molecules are responsible for the movement and in what direction?
Microtubules; Synthesis and assembly take place in the soma of the neuron; Anterograde (toward the nerve terminal) is accomplished by Kinesins; Retrograde transport (toward the nerve cell body) is accomplished by dynein
in general what is transported anterograde?
Transmitters and Structural proteins
in general what is transported retrograde?
Debris viruses; and growth factors
in Axonal guidance what it the first area called; what does it do?
The growth cone; establishes a pathway and detects physical cues to continue to grow or degrade
in terms of guidance signals; what are three broad types and some examples of each?
Adhesive substrate-bound cues (the roadway) CAMs and ECM; Repellent substrate-bound cues (the roadways guard rails) Slits and ephrins Chondroitin sulphate proteoglycans; Diffusible chemotropic cues (Road signs) class guidance molecules (netrins and semphorins) neurotransmitters growth factors
A nerve is usually made up from a variety of fascicles what are the layers around these fascicles?
Epineurium (surrounds the many fascicles that make up the anatomical nerve); perineurium (surrounding individual fascicles); endoneurium (surrounds the nerve fibbers them selves)
even if an axon is damaged the conduit made up of What and what will often survive and provide a pathway for regrowing axons?
even if an axon is damaged the conduit made up of Perineurium and epineurium will often survive and provide a pathway for regrowing axons?
what can trigger wallerian degeneration in the PNS?
Triggered by severe nerve injury (trauma; transection; toxins; inflammation and demyelination; neurodegeneration) or blockade of axonal transport
in Wallerian degeneration describe what happens in the neuron soma and proximal axon.
there is an aggregation of protein in the soma; trophic factors prevent proximal axon loss; macrophages invade injury and secrete cytokines and secretion of extracellular proteins by Schwann cells cause a proximal axon to sprout within around 96 hours
in wallerian degeneration describe what happens in the distal axon.
Degeneration over a 1-2 weeks; Glial cells push synaptic terminals away from the muscle; the myelin sheath degrades; Schwann cells begin to remove debris; but the Schwann cells and endoneural tube persists as support/guides for 1-2 months
what is the main tool in determining peripheral nerve damage/demyelination
Electrophysiology
what is the prognosis of a injury that leaves the axon and nerve structure intact but creates a nerve conduction block in the PNS?
Prognosis is very good; 3-4 month recovery
what is the prognosis of a injury that leaves axonal damage but the nerve structure is intact in the PNS?
prognosis is good; axon regrowth at ~1 mm/day from injury to tissue target
what is the prognosis of an injury that has axonal and nerve structure damage in the PNS?
variable; needs surgical nerve reconnection followed by axonal regrowth; up to 18 mths
what does surgical approximation of a peripheral nerve aim to do?
Realign the nerve fascicles for axon guidance
what are four aids to peripheral nerve repair?
Fibrin tissue glue; nerve conduits; electrical stimulation; nerve graft
how does fibrin tissue glue help with peripheral nerve repair
provides extracellular matrix around the nerve approximation; prevents invasion of scar tissue
what are the two types of nerve graft
isograft uses sensory nerves from the same patient; allograft uses processed nerve from donor
how do nerve conduits help peripheral nerve repair?
They provide a guidance path for axonal growth; prevent scar tissue invasion and axon escape; creates a nerve growth factor rich local environment;
CNS axons have the capacity to regenerate but?
the environment inhibits this
what are two factors that inhibit axon growth in the CNS?
glial cells secrete inhibitory factors; formation of glial scar block axonal growth;
what are three stem cell sources?
Pluripotent stem cells from embryonic tissue; induced transformation of tissue stem cells; the adult brain has a small number of stem cells
where are pluripotent stem cells derived from?
blastocyst or embryonic tissue
where do induced pluripotent stem cells come from?
Genetic reprogramming of adult cells (skin)
what are some benefits to induced pluripotent stem cells?
Avoids rejection problems; less ethical concerns
what are some issue with using adult neural stem cells?
there are few present; identification and harvesting is very difficult; they may have some significant DNA errors
describe neural interface systems
Brain activity can be used to directly control muscle; computers or other assistive or prosthetic devices
