Nerve Regeneration and Repair Flashcards
(31 cards)
3 ways to Damage Nervous system:
- Acute injury
- degenerative diseases
- loss of myelin
Classify the disease (degernative or loss of myelin): Parkinson’s, Multiple sclerosis, ALS
Parkinson’s is degernative
ALS is degenerative
MS is loss of myelin- more specifically loss of oligodendrocytes causing decrease in speed of conduction
Where in the brain is grey and white matter loss in AD?
temporal lobe in the area of hippocampus
What protein is over expressed in AD patient and TBI patient?
Tau
What long term changes are caused by closed head injuries - damage to brain tissue and loss ?
changes in mood, cognitive function,and depression
Why is repair of the damaged nervous system limited?
- Neurons can be damaged so that they cannot be repaired, saved, or replaced
- The immediate cellular environment does not aid in the repair process in the CNS (though it does in the PNS)
What are the requirements of nerve regeneration?
- Nerve CELL BODY must survive
- CLEARANCE of damaged tissue (distal axon, myelin breakdown products, vessel remnants etc.)
- An ENVIRONMENT that promotes axonal growth
- ## Axonal GUIDANCE cues
What is the significant role of perineum in nerve regeneration?
it is composed of ECM proteins that can promote axon elongation and sprouting after injury
It also secretes Neurotrophins which help neurons survive
It also phagoocytose detached debris
Name the connective tissue that surrounds axons in the peripheral nerve
Epineurium
What nerve type is Schwann cells associated with?
myelinated
Which cells afre the myelinating cells in the CNS?
OLIGODENDROCYTES
How fast does an axon grow?
1 mm per day, 1 inch/month
Describe the 5 basic steps of Wallerian degerneation and axon regernation after a peripheral nerve injury
- denervated Schwann cells release myelin, proliferate, secrete cytokines/trophic factors, phagocytose debris
- Cell body hypertrophies, displacing nucleus eccentrically
- Resident Macrophages are activated and they recruit hematogenous macrophages which clean up myelin and axon debris while producing facctors that facilitate Schwann cell migration and axon regernation
- Injured axons form a growth cone and regenerate along bands of Bungner
- If axon is able, it connects with peripheral targets
What is importance of Bands of Bungner?
It is formed by Schwann cells and they are tubes that provide a permissive growth environment. It is like a guidance channel axons to denerevated muscle targets
which is harder to repair? Nerve cut or crush?
cut
which is more common and how does it occur? Nerve cut or crush?
crush/compression due to acute trauma in SC
What guidance cue plays a significant role in facilatiting PNS nerves to reconnect with muscle when regenerated?
Acetylcholine receptors that remain on muscles where axons previously terminated. Schwann cells line up with AchR
which 3 nerve regeneration requirements are not seen in CNS nerve injury?
- Clearance mechanisms
- Effective environment for axonal growth
- Axonal guidance cues
What is Wallerian degernation
the process of removing damaged axons, myelin debris and damaged cells (slow in CNS b/c oligodendrocytes don’t help clean as Schwann cells do)
What is the benefit and disadvantage of a glial scar?
It helps limit tissue damage but it is repulsive to axonal growth because it contains CSPGs. This produces a physical and chemical barrier that interferes with axonal regrowth and cellular repair
What is a glial scare formed by?
reactive astrocytes, and other cells producing Chondroitin Sulfate Proteoglycans (proteins core _ Glycoaminoglycan sugare side chains)
What stimulates production of CSPGs by astrocytes?
Injury and inflammation
What strategies to enhance repair of damaged spinal cord are emerging?
- Biomaterials: to provide a growth promoting substrate for axons
- Growth factor targets: to promote neuronal survival and axonal sprouting (ex. Peripheral nerve graft is a source of growth factors)
- Agents that change the local environment in lesion
- Agents to promote remyelination after injury
- Cell replacement therapy to replace neurons or oligodendrocytes (STEM CELLS)
What enzkme removes sugar side chains from CSPGs, creating a permissive regernation environment?
Chondroitinase
