9. Neurohistology and response to spinal cord injury

Question 1

What are the two principal cell types of nervous tissue?

Answer 1

Neurones

Neuroglia (supporting tissue)

Question 2

Perikaryon?

Answer 2

Cell body

Question 3

In the CNS the cell bodies of neurones which reside in the grey matter are called…

Answer 3

Nuclei

Question 4

In a Nissl stain why is the axon not blue?

Answer 4

As it doesn’t contain ER or polyribosomes i.e. there are no proteins there to stain

Question 5

composition of the granule layer of the cerebellar cortex?

Answer 5

Granule cells (most abundant neuron in brain), Golgi cells

Most inner layer of the 3

Question 6

composition of the purkinje layer of the cerebellar cortex?

Answer 6

Purkinje cells

Middle layer of the 3

Question 7

composition of the molecular layer of the cerebellar cortex?

Answer 7

Basket cells
Stellate cells
Fibres from above cell types

Most outer layer of the 3

Question 8

What are the purkinje neurons of the cerebellum and what is their appearance role?

Answer 8

What are they? Purkinje neurons are multipolar neurons and are the largest cell in the cerebellum

Appearance? They are have pear-shaped cell bodies and a distinctive dendritic tree which expands into the molecular layer

Role? They receive afferent information from other areas of the CNS

Question 9

Name 4 neuroglia cells of the CNS?

Answer 9

Astrocytes
Oligodendroglia
Ependymal cells
Microglia

Question 10

Name 2 neuroglia of the PNS?

Answer 10

Schwann cells and satellite cells

Question 11

Which neuroglia form myelin sheaths around axons?

Answer 11

Oligodendroglia (CNS)
Schwann cells (PNS)

Question 12

Astrocyte:
Found in?
Role?
Types?

Answer 12

Only found in CNS

Provide structural and metabolic support for neurons. Also involved in the blood-brain barrier.

Types:
• Fibrous (in white matter)
• Protoplasmic (in gray matter)
• Müller glia (in retina)
• Radial glia (specialised cells in developing CNS)

Question 13

Role of astrocytes in the the blood-brain barrier?

Answer 13

Astrocytes form glial-limiting membrane around blood vessels and along CNS surface.
On internal surface of blood vessel is a barrier composed of endothelial cells joined by tight junctions

ROLE? Prevents diffusion of solutes and fluid into brain and spinal cord.
Entry of 02 and Co2 and lipid soluble molecules. Above 500 daltons is not allowed

The integrity of this BBB is highly dependent on astrocyte ‘end feet’

In CNS

Question 14

What are ependymal cells?

Answer 14

Ciliated cuboidal epithelial cells which line the ventricle as part of plexus and secrete (also reabsorb) CSF

In CNS

Question 15

Define CSF

Answer 15

(cerebrospinal fluid) – clear, cell-free fluid produced in choroid plexus

Question 16

What is the role of microglia? How do they become activated?

Answer 16

Support cells of the CNS

Role? Serve an immune function within the CNS much like macrophages, able to phagocytose cell debris in response to injury

Activation? Normally exist as ‘resident microglia’ but become ‘activated’ upon CNS damage and actively move towards sites of injury
Release cytokines which can both help and hinder recovery

Question 17

Role of oligodendrocytes?

Targeted in which diseases?

Answer 17

Role? Form myelin sheath around CNS axons, with one oligodendrocyte able to myelinate SEVERAL axons

Targets when? Diseases that affect oligodendrocytes include multiple sclerosis and leukodystrophies

(One of the last cell types to form during development)

Question 18

Role of schwann cells?

Answer 18

• Form myelin sheath around PNS axons, with ONE Schwann cell able to myelinate ONE axons
• Plays key role in organisation of connective tissue sheaths around peripheral nerves during development and regeneration

Question 19

Benefits of myelination?

Answer 19

Insulation
Protection
Enhanced conduction velocity for APs

Question 20

What happens to axons NOT myelinated in the PNS and CNS?

Name 3 types of axons not myelinated

Answer 20

PNS: Schwann cells ‘envelope’ unmyelinated axons contacting 1 or more axons
CNS: Unmyelinated axons are not associated with glial cells

Unmyelinated axons have ‘continuous conduction’ of action potentials due to passive current flow (low conduction)

E.g. Sensory fibres carrying pain, temperature, itch

Question 21

Ganglia are aggregations of nerve cells outside the…

Answer 21

CNS

Question 22

What covers the root ganglia?

Answer 22

Cranial nerve and dorsal root ganglia are surrounded by a connective tissue capsule, which is continuous with the dorsal root epi- and perineurium
Individual ganglion cells are surrounded by a layer of flattened satellite (fibroblast) cells

Question 23

What is the connective tissue structure surrounding peripheral nerves?

Answer 23

These bundles possess a thick sheath of connective tissue the EPINEURIUM, each bundle is surrounded by a PERINEURIUM and each nerve fiber is surrounded by a ENDONEURIUM

Question 24

Describe the motor neurons in the spinal cord?

Answer 24

Cell bodies of MULTIPOLAR motor neurons are LARGE and are found in the ventral horn of the spinal cord

They display a large pale staining nucleus and a prominent nucleolus and nissl bodies

Question 25

Differences in repair ability between PNS and CNS?

Answer 25

Peripheral nerves can be repaired after injury, with a large degree of regeneration expected due to intrinsic capabilities CNS axons CANNOT be repaired

Question 26

What is Wallerian degeneration? Where is it most effective and why?

Answer 26

Clears debris and lays the foundation for regrowing nerve fibres In both the CNS and PNS. This process is not efficient in the CNS, resulting in failed repair after injury. CNS environment has a further abundance of inhibitory factors contributing to failed repair.

Question 27

Process of Wallerian degeneration upon injury to nerve fibre in the PNS?

Answer 27

1. Injury 2. Fragmentation of distal axon and myelin sheath. Schwann cells become reactive, proliferate, while macrophages 3. Schwann cells express/ secrete growth factors and form Bands of Büngner. Nerve fibres grow towards and through the Bands. 4. Nerve fibres reconnect with end organs and are remyelinated by Schwann cells.

Question 28

Process of Wallerian degeneration upon injury to nerve fibre in the CNS?

Answer 28

1. Normal axon 2. Injury. 3. Fragmentation/disintegration of distal axon and myelin sheath. Microglia and astrocytes become active. Inflammation ensues. Macrophages begin to remove debris. 4. Myelin debris is not completely removed, although oligodendrocytes survive. Glial scar is formed by reactive astrocytes. 5. Regeneration fails as growth of transected axons is inhibited by persistent myelin debris and glial scar.

Question 29

How is the glial scar forms in the CNS?

Answer 29

In the CNS after traumatic injury, astrocytes become 'reactive' Reactive astrocytes --> - Become hypertrophic - Increase expressions and secretion of inhibitory molecules including chondroitin sulfate proteoglycans (CSPGs) - Increase expression of normal molecules (e.g. Glial fibrillary acidic protein, GFAP) The result? Formation of a glial scar This glial scar + myelin debris = area which growing axons cannot pass through

Question 30

What is the "signature of failed axon regeneration" and how does it form in CNS injury?

Answer 30

Axons do attempt to regrow, but fail in response to the inhibitory environment and a lack of growth-promoting molecules End result is growing axons turning away from the lesion and/or having reactive ‘end bulbs’ (swellings of accumulated organelles) at their tips, a signature of failed axon regeneration

Question 31

Role of glial cells in nervous system repair?

Answer 31

* Schwann cells contribute to successful Wallerian degeneration and repair in the PNS * Astrocytes in the CNS contribute to the inhibitory glial scar and failed repair in the CNS * Oligodendrocytes in the CNS contribute myelin debris and failed repair in the CNS * Glial cells are segregated to the CNS or PNS at the glial limiting membrane at the dorsal root entry zone