W 3.1 - repair and regeneration in the nervous system

neuroscience, winter '26

CNS healing is:

reorganization rather than regeneration

PNS healing is:

regeneration

axons in the periphery grow:

through vacated peripheral nerve sheaths

in the CNS, ____ cells actively inhibit axon growth

glial

neural stem cells in the brain are constrained in their ability to ___, _____, and _____

divide, migrate, differentiate

what response further inhibits extensive growth in the nervous system?

immune

return of function likely represents _______ circuits rather than the _____ circuits

change of intact, repari of damaged

what is use-dependent plasticity

it takes high repetitions of specific tasks in order to reorganize the brain to support he impacted part

what are the 3 types of nervous system repair or regeneration

regrowth of axons, restoration of damaged CNS cells, neurogenesis

where does regrowth of axons occur?

in the PNS

what is necessary for a damaged CNS cell to regrow and what is it called?

the cell body has to be intact, called sprouting

why does sprouting typically fail?

glial overgrowth limits the growth, preventing access to necessary trophic factors and causing apoptosis

why does neurogenesis not work very well?

it’s hard to integrate the new neuron into the existing system in the CNS

why does glial overgrowth happen?

insulates intact tissue from further damage due to inflammation

what role to inflammatory cytokines play in failure of CNS sprouting

suppression of dendritic/axonal regrowth mechanisms

what kinds of neurons can regenerate throughout adult life?

peripheral olfactory receptors

how to glial cells prevent axonal regrowth?

by creating a scar over the axon and physically blocking it from growing

which neuroscientist performed a nerve transection and reapposition on himself to study peripheral nerve regeneration?

Henry Head

the speed and precision of peripheral nerve recovery can be facilitated by what?

surgical reapposition of the two severed ends of the nerve

what is the approximate average speed of axonal regrowth in a peripheral nerve?

1mm/day

what factor can increase the speed of regrowth of axons in the PNS?

preservation of the axonal sheath

true or false: the adult peripheral nerve repair is identical to infant peripheral nerve repair

false

what 2 cells are primarily responsible for contributing to growth and reinnervation in the mature NS?

Schwann cells and macrophages

how do Schwann cells and macrophages contribute to regrowth in the PNS?

secretion of molecules to guide the regeneration of the intact proximal axon

Schwann cells are the primary guide for regrowth in what kind of nerve injury?

severance of a nerve

nerves in (cut/crush) injuries heal faster than those in (cut/crush) injuries

crush, cut

what are the 2 differences between embryonic peripheral nerve repair and adult peripheral nerve repair

larger distances and specified targets in the adult

_____ and _____ can influence peripheral axon regrowth

activity, use

what role do NGF and BDNF play in peripheral nerve regeneration?

enhance necessary trophic signaling for target recognition and synaptogenesis

mature CNS neurons have the capacity to do what in the periphery?

modify gene expression and respond to appropriate cues

mature CNS neurons can reactivate the expression of what 2 molecules at the damaged NMJ?

NGF and BDNF

how long do original neuromuscular synaptic sites remain intact after an injury?

weeks

what are 4 different types of injury to the CNS?

trauma, local ischemia, global ischemia, neurogenerative diseases

what is the trigger to the cascade that actively stops regrowth in the CNS?

apoptosis

activation of cell enzymes, especially _____, cause __ ____ in the CNS to prevent regrowth

capsase-3, cell death

what 2 events occur in CNS neuronal regrowth that make it unsuccessful as compared to regrowth in the PNS?

glial proliferation to actively inhibit growth; upregulation of growth-inhibiting molecules similar to chemorepellants

what is autophagy?

an intermediate response to cellular stress that can either prevent or lead to neuronal degenerationo

how can autophagy both prevent and preclude neuronal degeneration

by altering activity to accommodate metabolic demands and move as close as possible to a state that does not trigger apoptosis, cleaning up and also enhancing neuronal survival

what is glutamatergic overstimulation

a major source of cellular stress caused by bursts of abnormal activity post-local brain damage

define excitotoxicity

elevated neuronal activity and its consequences

excitotoxicity can lead to":

neuron death

why would a glial scar be a protective mechanism?

due to lack of extra space for inflammation without further damage from the pressure

injury to CNS tissue elicits a response from what types of glia? (3)

astrocytes, oligodendrocytes, microglia

in addition to glial cell growth, what other cell adds to the mass and helps establish the glial scar?

macrophages

what is the role of interleukin-1 with the formation of a glial scar

it modulates expression of several immune mediators that reinforce the inflammatory state resulting in a glial scar

there is evidence of some neurogenesis in what 2 parts of the adult brain?

hippocampus and olfactory bulbs

true or false: adult cortex is successful in the generation of new neurons

false

in the CNS, new nerve cells are primarily _____

interneurons

where do new interneurons arise from?

stem cells close to the surface of the lateral ventricles

why does neurogenesis not take hold well in the adult brain?

the main focus is stability so the brain doesn’t allocate resources to new neurons

what is functional remapping?

changes in cortical representation can occur in response to physiologic changes in sensory or motor experience

how can functional remapping occur?

increase/loss of use of a particular body part can allocate more/less cortical space to it

in functional remapping, the ____ _____ will change the _____

driving circuitry, cortex

true or false: functional remapping is a permanent change until the next training target

false (will “atrophy” back to original map)

functional mapping is a change in___ that attributes to the ___

synapses, shifting

expanse of one part of the cortical map is ________ other parts

at the expense of

functional recovery after brain damage is due to:

adjacent regions adapting to compensate for loss of function based on changing patterns of activation

for neuronal change, you need the task to be:

high reps, challenging, salient

how many repetitions did the monkeys in Nudo’s study perform to see neuronal change?

12,000

in order to try and gain maximal recovery post-ischemia, what must occur?

utilization of the affected side

why is it important to use the affected side when training for recovery?

prevention of loss of cortical area for the functional tasks

the motor cortex is organized in:

topographic maps

what are 3 pieces of evidence for adaptive plasticity in motor maps as seen in the Nudo study

repetitive artificial stimulation over time was represented by a larger cortical territory; spatial distribution of hand movement correlates to hand preference; learning complex skills procured greater cortical change than simple task repetition

how does Nudo’s study show alteration in motor maps is possible after cortical injury

the spontaneous recovery group had further loss of cortical territory adjacent to the injury site while the forced repetitive use group had behavioral recovery of hand function and prevented loss of cortical territory adjacent to the injury site