REPAIR OF NERVE

FIBRES
Submitted to,
DR. R.V Prasad
Prof. & Head
Dept. of Veterinary Anatomy &
Histology.

Presented by,
Divya. Nutan
MVHK-1329

INTRODUCTION

Neurons in the PNS can regenerate

their axons.
Neurons in the CNS have a limited
capacity to
regenerate their
axons.
If the cell body is damaged, the
neuron is lost. There is no cell
division in adult brain to replace the
lost neuron.

If the axon is
severed at a distance from the
cell body, then the cell body is
lost,
but there is a chance that the
axon
will regenerate, primarily in PNS
The postsynaptic,
and the presynaptic, neurons are
also affected and may degenerate

Types of glial cells

Myelin forming cells: (myelin is important for
conduction of nerve impulses).
oligodendrocytes (CNS) :are inhibitory to axon
regrowth in adult CNS regeneration.
Schwann cells (PNS) : are supportive to axon
regrowth and are releasers of growth factors.
Astroglia :during development supports axon
growth and cell migration. In injury accumulates in
scar at the site of injury & releases excess matrix.

Cont....
Microglia (resting) and
macrophages (active) cells of
immune system, similar to
monocytes.

Types of glial cells

1. Myelin-forming:
a. Oligodendrocytes
(CNS)

b. Schwann cells
(PNS)

2.

Astrocytes

REACTIONS TO INJURY WITHIN THE NEURON

MINUTES after injury
- synaptic transmission off & cut ends swell

Hours after injury..

SYNAPTIC TERMINAL DEGENERATES

neurofilaments

Vesicles Synaptic
accumulate

Hours after injury..

ASTROGLIA SURROUND SYNAPTIC TERMINAL

NORMAL

The damaged neuron is affected by injury

as well as the neuron pre- and postsynaptic to it

Days to weeks after injury

What is wallerian degeneration?

Wallerian degeneration occurs in the axon stump
distal to a site of injury and usually begins within
2436 hours of a lesion.
After injury, the axonal skeleton disintegrates and
the axonal membrane breaks apart.
The axonal degeneration is followed by
degradation of the myelin sheath and infiltration
by macrophages.

Cont.
The macrophages, accompanied by Schwann
cells, serve to clear the debris from the
degeneration.
The nerve fiber's neurolemma does not
degenerate and remains as a hollow tube.
Within 4 days of the injury, the distal end of the
portion of the nerve fiber proximal to the lesion
sends out sprouts towards those tubes and these
sprouts are attracted by growth factors produced
by Schwann cells in the tubes.

Cont

If a sprout reaches the tube, it

grows into it and advances about
1mm per day, eventually reaching
and reinnervating the target tissue. If
the sprouts cannot reach the tube,
for instance because the gap is too
wide or scar tissue has formed,
surgery can help to guide the sprouts
into the tubes.

Cont.
This regeneration is much slower in
thespinal cordthan in PNS. The
crucial difference is that in the CNS,
including in the spinal cord, myelin
sheaths are produced by
oligodendrocytes and not by
Schwann cells.

Regenerating axons
form many sprouts,
some of which find
Schwann cell tubes

Changes in the axon during

degeneration and regeneration

 Macrophages clean debris, release mitogens

which stimulate Schwann cells to divide.
New Schwann cells repopulate nerve sheaths
also produce laminin (growth-supportive
extracellular matrix)

Macrophages release interleukin which

stimulates the Schwann cells to make Nerve
Growth Factor which stimulates axon
regeneration.

Cont.

Axons
sprout, and
some
sprouts enter
new
Schwann
cell tubes.

Axonal
growth
cones
successfully
grow.

1.

Factors responsible for

limited regenerative
capacity
of
CNS
axons
Growth is impeded by increase in

substances like

myelin proteins (NOGO, MAG, Omgp)

inhibitory proteoglycans
2. Intracellular growth factors such as GAP-43
(important for intracellular signalling/growth
cone advance) are low

Cont
3. Growth factors have different distributions compared to young
brain.
4. Normally growth-supporting extracellular matrix laminin ,is
sparse.
5. Glial cells inhibit growth of axons.Oligodendrocytes are the
most inhibitory.

How to determine whether axons have regenerated?

Descriptive tests
based on microscopy.

Functional tests,
including behavioral
assays.

Therapeutic Strategies:
1. Transplant/ implant : into or near site of
injury
- fetal tissue (containing immature neurons and glia)
or stem cells, with potential of becoming either
- good glia: olfactory ensheathing glia.
2. Direct delivery of growth factors to promote
axon regrowth .
3. Application of neutralizing activity (e.g.,
antibodies ) to combat inhibitory glia.

Olfactory ensheathing cells, with properties of CNS and PNS glia,

transplanted into transected corticospinal tract
OEC

OEC

And recovery of function occurs after transplantation

(caveat: some axons might be spared)
(Rev: Raisman, 2001, Nat. Rev. Neurosci. 2: 369;
Also Li et al., 2003, J. Neurosci. 23:7783)

+myelin
antibody

Axons can regenerate if myelin/oligodendrocytes

are neutralized by antibody application .