Neural Recovery

strategies used by the neural system to grow

redundancy, compensation, regeneration of axons

axotomy

severing of the axon

consequences of axotomy

chromatolysis, wallerian degeneration, transneuronal degeneration

initial steps of neuron degeneration after axotomy

loss of membrane integrity so extra and intracellular contents flow freely → synaptic transmission fails due to membrane failure and loss of voltage difference → proximal end membranes fuse and the axon pulls away

wallerian degeneration following axotomy

microglia (CNS) and macrophages (PNS) recruited and phagocytose the debris

why is the PNS faster at cleaning up debris after an axotomy

macrophages are better scavengers, schwann cells are more easily broken down than oligodendrocytes

how long does it take to remove debris after an axotomy

PNS: 3 weeks, CNS: 1-2 months

chromatolysis following axotomy

cell body swells and nucleus migrates away from the axon → glial cells invade synapses, dendrites increase excitability, protein synthesis increases

determinant of the likelihood of neuron survival after axotomy

how quickly chromatolysis occurs

transneuronal degeneration

other cells in the pathway as well as schwann cells and oligodendrocytes die in addition to the nerve with the severed axon

cause of anterograde transneuronal degeneration

debris and chemicals in the area, loss of significant input

cause of retrograde transneuronal degeneration

reduction of neurotropic growth factor

steps of axonal regeneration

vacant nerve tract created → schwann cells divide and fill in the gaps → secrete basal lamina → axons sprout neurites that form growth cones → axon grows in the direction of the target

CNS limitations that affect axonal regrowth

no schwann cells (no basal lamina to follow), limited sprouting (limited growth cones), poor clearance of debris, glial scarring of growth cones trying to get to the target

growth signals of axogenesis

chemoattraction/repulsion, contact attraction/repulsion (same as during development)

aftermath of axogenesis

pruning of non-target synapses, strengthening of axons going to the target

growth factor

any substance produced by a cell to aid in the survival of another cell

neurotropic growth factor (NGF)

any substance produced by a cell to aid in the survival of a neuron

NGF independent neurons

immature neurons that don’t need NGF to survive

NGF dependent neurons

mature neurons that require NGF to survive

criteria for a neuron to be called mature

once it is exposed to NGF it is permanently dependent on it

characteristics of NGFs

secreted by target cells, transported to cell body via axon

consequence of loss of NGF in dependent neurons

apoptosis (programmed cell death)

barrier to apoptosis of all cells in the PNS

macrophages secrete IL-1 that maintains the schwann cells, schwann cells proliferate and secrete NGF

why do we see more apoptosis in the CNS

no macrophages so no IL-1, no schwann cells, proteins suppress axonal growth

characteristics of plasticity in the nervous system

sometimes by growing new axons/synapses, most often by unmasking pathways that already exist