CENTRAL NERVOUS SYSTEM INJURY

REVISION QUESTION

1. What do brain, and spinal cord injury have in common?

ANS:

a) Damage to or loss of neurons and neural tissue

b) Damage to or loss of axons

c) Damage to or loss of synapses

2. What do brain injuries have in common

ANS:

- Cell biological reactions in the damaged neuron

Are presynaptic and postsynaptic

- If the axon is severe or damaged close to the cell body, the cell body may die.

- If the cell body survives, the axon does not regenerate

- The postsynaptic and the presynaptic neurons are also affected and may degenerate

- There is no cell division in adult brain to replace the lost neurons.

3. What does it mean that CNS neurons do not divide?

ANS:

Once neurons become mature, they do not re-enter the cell cycle and divide – the number of nerve
cells remains constant throughout a humans’ entire lifetime.

4. What are the difficulties in replacing lost neurons in CNS?

ANS:

- The replacing of neurons can be done through

a) Endogenously b) Artificially

- However, it is very difficult due to the following factors

a) diversity of neuron types

b) vast neural networks involving many neurons

c) neurons cannot exist without connecting to other cells

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 d) Though neuron did replicate it would still die because it would lack the trophic support
necessary for survive.

5. Because neurons in CNS do not divide, many therapeutic interventions and research
investigations are aiming at protecting the neurons from dying. Identify and describe three ways
to protect the neurons from dying.

ANS:

1) Tissue plasminogen activator (TPA) – a clot buster that can restore blood flow following stroke
(given within three hours)

2) Neuroprotective agents – range from antioxidants to steroids – aimed at mitigating the effects of
oxidative stress, restoring cellular homeostasis and blocking programmed cell death (apoptosis)

3) Cell replacement therapies.

5. Identify the genes associate with RAG induction?

- STAT3
These are all examples of
- DLK-1
genes in neurons whose
- ATF3 expression induce axon
- KLF4 regeneration
- KLF7

- SMAD1

- SPRR1A

6. Identify genes associate with axon regrowth?

- PTEN/mTOR

-HDAC5 These are all examples of

- SOCS3 genes in neurons whose
- EFA-6
expression induce axon
regrowth

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7. Neuron in the PNS do regenerate. Describe why neurons in CNS do not regenerate?

ANS:

- The regeneration of axonal processes in the central nervous system is limited by the
following factors

a) intrinsic mechanisms

- Regulation of gene expression after CNS development – RAGs (Regeneration Associate Genes) are
down regulated while Growth inhibitory genes are up regulated.

b) Extrinsic mechanisms.

- Axon extracellular environment is not optimal for regeneration

- Myelin debris in the injured territory signal to the axon and prevent its regrowth: Myelin derived
factors such as:

a) MAG – Myelin-associated glycoprotein -

inhibit regeneration Myelin derived molecules
that prevent axon growth
b) OMgp - Oligodendrocyte-myelin glycoprotein
- inhibit regeneration

c) Nogo - inhibit regeneration

- Also, astrocytes produce chondroitin sulfate proteoglycans (CSPGs) which both signal to the axon
and form a “scar” barrier for regeneration.

- Receptors in the axon – Nogo Receptor (NgR), TROY, LINGO, PirB, and PTP- sigma -transduce signals
intracellularly to halt growth.
RECEPTORS that prevent
growth

8. How can a neuron be influenced into a regenerative state in therapeutic targets?

- therapeutic targets

a) Reprograming neurons through epigenetic modulators have shown promise – e.g. histone
acetylation, DNA demethylation.

b) The removal of the scar in the neuron cells particularly in the Myelin

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9. List and describe example Intrinsic and extrinsic mechanism processes that have made it
possible to identity molecules that can targeted to make axon growth conditions more
permissible.

a) Intrinsic Mechanisms (Refers to genes that promote axon regeneration)

The axonal growth state is determined by gene expression; thus, studies have focused on
determining genes that are important for growth. Targeting these genes can promote regeneration

For example: Lack of RAG induction (e.g. STAT3, DLK-1, ATF3, KLF4, KLF7, SMAD1, SPRR1A).
Inhibitors of axon regrowth (e.g. PTEN/mTOR, HDAC5, SOCS3, EFA-6)

b) Extrinsic Mechanisms (Refers to Myelin derived molecules & Chondroitinase enzyme)

- Immunotherapy and receptor blocking peptides against Nogo, MAG and OMgp.

- or inhibition of the downstream intracellular pathway-RhoA

- similarly breaking down the chondroitin sulfate proteoglycan scar with chondroitinase enzyme
promotes regeneration.

10. The Gray and White matter in the brain and spinal cord a predominantly composed of:

ANS:

Gray

- Composed of Neuronal cell body

White

- Composed of myelinated axons

11. Identify and describe the three main types of CNS injuries

1) Traumatic Brain Injuries (TBI)

TBI defines as an alteration in brain function, or other evidence of brain pathology, caused by an
external force.

Traumatic brain injury is a specific type of damage to the brain that results when the head:

• Hits a stationary object (e.g. windshield in a car crash)

• Is hit (e.g., assault)
• Is penetrated (e.g., gunshot injury)
• Is violently shaken by external force (e.g., shaken baby syndrome)
• Receives a concussive blast (e.g. explosive device)

Often included are individuals with other types of postnatal acquired injuries, such as strokes and
aneurysms.

Mild traumatic brain injury can cause axons to stretch, disrupting their functions is that diffuse white
matter injury.

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Greater forces can result in damaged synapses, and even cutting of axons.

2) Stroke

Stroke occurs when there is an interruption of blood supply to the brain. The brain requires
continuous supply of oxygen and glucose for neurons to functions properly. If the blood flow is
interrupted the following are the results:

• Neurologic metabolism is altered in 30 seconds

• Metabolism stops in 2 minutes

• Cell death occurs in 5 minutes

The three ways in which stroke can occur are:

The type of stroke is classified based on the underlying pathophysiologic cause which are

1) Transient ischemic attack (TIA)

2) Ischemic

- Thrombotic

- Embolic

3) Hemorrhagic

If a person has an ischemia stroke, he or she can be treated to minimise long-term problems within 3
hours. This may be due to micro-emboli (abnormal particles such as air bubbles blocking the blood
flow in the blood vessels).

3) Spinal Cord Injury

The spinal cord injury occurs due to the following factors

a) Spinal cord injury, the cord may be cut-cross or dislocated

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 - Dislocation and movement of vertebrae can cause the cord to be cut
- Penetrating injuries, e.g. gunshot or stab wounds

b) Or the cord may be compressed or contused (Injure the underlying soft tissue or bone of)

- Fractures, crushes, or movement of vertebrae can cause the cord to be compressed and contused

- often the result of impacts

The spinal cord injury results in dysfunction like:

• May involve partial of full paralysis

• Partial/full loss of motor function

• Partial/full loss of sensory function

• Partial/full loss of autonomic function

The clinical effects of stroke are listed below

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