Lecture 7-Repair and Regeneration

Question 1

Three Types of Neuronal Repair

Answer 1

1) Regrowth of axons
2) Restoration of damaged neurons
3) Genesis of new neurons

Question 2

In peripheral nerve regeneration, what happens when peripheral axons are severed?

Answer 2

The neuron typically regenerates the distal portion of the axon to reestablish the connection (re-growth of axons).

Question 3

What is the immediate impact of a CNS injury on axons and dendrites?

Answer 3

Axons and dendrites tend to degenerate, resulting in the loss of connections between neurons.

Question 4

What are the three different cell types involved in the post-injury recovery process in the nervous system?

Answer 4

The three cell types are neurons (some of which may die), glial cells like astrocytes (which can form scars), and microglia (responsible for removing debris and dying cells).

Question 5

What is the consequence of the presence of many glial cells, especially astrocytes, around an injury site in the CNS?

Answer 5

The presence of many glial cells around an injury site indicates the development of a scar in the CNS,inhibit the regrowth of nerve fibers

Question 6

How does neuronal replacement occur in the context of nervous system injury?

Answer 6

Neuronal replacement occurs through the recruitment of stem cells to the injury site, where they divide and generate new neurons to replace the damaged ones.

Question 7

What did Henry Head’s experiments demonstrate regarding the regenerative ability of the nervous system?

Answer 7

Henry Head’s experiments demonstrated the regenerative ability of the peripheral nervous system (PNS).

Question 8

What did Henry Head initially do in his experiments to demonstrate the regenerative ability of the peripheral nervous system (PNS)?

Answer 8

Henry Head severed a peripheral nerve, specifically the radial nerve, in his own arm.

Question 9

What was the initial effect of the nerve severing in Henry Head’s experiments on his arm?

Answer 9

The nerve severing resulted in a loss of sensation in certain areas of his lower arm and hand, which became insensitive to painful stimuli and light touch.

Question 10

How did sensation change over time in Henry Head’s experiments?

Answer 10

Over a period of 2 to 6 months, Henry Head observed a significant recovery of sensation in his hand and thumb.

Question 11

What did Henry Head observe within the region that regained sensation in his hand and thumb?

Answer 11

Within the resensitized region, Henry Head identified various marks or spots that were either “hot” or “cold” in terms of sensitivity to stimulation.

Question 12

What is the role of macrophages when a nerve is cut?

Answer 12

Macrophages move into the area to help clear away dead cells and debris by engulfing and digesting them

Question 13

What can happen if there is a deficiency in macrophages in the context of nerve injury?

Answer 13

A lack of macrophages during nerve injury can lead to uncontrolled cell death and tissue damage due to the buildup of debris, triggering inflammation and oxidative stress.

Question 14

What is the role of Schwann cells in the peripheral nervous system (PNS)?

Answer 14

Schwann cells create myelin around axons in the PNS, facilitating faster nerve signal transmission.

Question 15

What is the internal membrane that holds together groups of nerve fibers wrapped by Schwann cells?

Answer 15

The internal membrane that holds together groups of nerve fibers is called the perineurium.

Question 16

What is the role of the epineurium in a peripheral nerve?

Answer 16

The epineurium is a connective tissue sheath that acts as a protective outer layer, enclosing and supporting bundles of nerve fibers within the nerve.

Question 17

Steps of Cellular Response to Cut in Peripheral Nerve

Answer 17

1) After a nerve injury, Schwann cells prepare to remyelinate the new axon.
2) Macrophages clear away myelin debris and dead cells.
3) The injured neuron activates genes related to growth, aiding in forming a new growth cone.
4) The growth cone advances toward its target, guided by various molecules.
5) Schwann cells proliferate and support axon regeneration and remyelination.

Question 18

What happens to myelinated axons in motor nerves that innervate muscle fibers when they are crushed or cut?

Answer 18

There is a period of denervation and loss of muscle function.

Question 19

What is the role of the superior cervical ganglion in the autonomic nervous system?

Answer 19

Receives signals from spinal cord preganglionic neurons and communicates with peripheral targets like the eye.

Question 20

What can damage to the CNS be caused by? Give 3 examples

Answer 20

-Traumatic brain injury (TBI): sports and wars
-Hypoxia due to ischemia: stroke
-Degeneration: Alzheimer’s, Parkinson’s disease

Question 21

What role do NMDA receptors play in apoptosis?

Answer 21

NMDA receptors contribute to apoptosis by facilitating excessive glutamate signaling, which can prompt cell self-destruction, especially under high excitatory signal conditions.

Question 22

How do cytokines contribute to neuronal apoptosis?

Answer 22

By triggering signaling pathways that promote cell death

Question 23

What happens when Bcl2 is inhibited in a cell?

Answer 23

Inhibition of Bcl2 allows the release of cytochrome c from mitochondria, which is a crucial step in the activation of apoptosis.

Question 24

What is the consequence of cytochrome c being released from mitochondria?

Answer 24

The consequence of cytochrome c release from mitochondria is the activation of caspase-3, which induces changes in the cell, ultimately leading to apoptotic cell death.

Question 25

What are some of the cellular changes observed during apoptosis?

Answer 25

Apoptosis involves the cell shrinking, DNA breaking down, forming blebs, and then dividing into apoptotic bodies that phagocytes clear.

Question 26

Reasons for Limited Regeneration in the CNS

Answer 26

1) Cell Death: CNS damage triggers cell death processes—necrosis (messy & damaging) and apoptosis (clean & controlled).
2) No Growth Signals: The CNS doesn’t restart the growth signals needed for repair after injury.
3) Stop Signals: After damage, the CNS produces more inhibitory molecules that prevent new growth.

Question 27

Steps in CNS Regeneration

Answer 27

1. Axon damage activates microglia and astrocytes.
2. Microglia remove debris.
3. Astrocytes form a glial scar, hindering axon growth.
4. CNS has limited axonal regeneration compared to PNS.
5. Glial scar inhibits CNS regeneration.
6. Oligodendrocytes remyelinate damaged nerve fibers.

Question 28

How does the response to injury in the CNS differ from the peripheral nervous system?

Answer 28

In the CNS, the injury response leads to inhibition of axon growth due to glial scar formation, unlike in the peripheral system where there is stimulation of axonal outgrowth.

Question 29

What role do microglia play following a CNS injury?

Answer 29

Microglia act as phagocytes, clearing away myelin and cellular debris from the site of injury in the CNS.

Question 30

Olidodenytrocytes Function in CNS Repair and Regeneration

Answer 30

Contributing to the remyelination of damaged axons, which can occur after the formation of the glial scar and the inhibition of axon growth.

Question 31

Similarities between CNS and PNS Regeneration

Answer 31

Inflammation and Immune Response: Both CNS and PNS injuries trigger an initial inflammatory response involving immune cells to clear debris.

Astrocyte Involvement: Astrocytes become active in response to injury in both the CNS and PNS.

Neuronal Regeneration: The primary goal in both CNS and PNS regeneration is to restore damaged neurons.

Question 32

Differences in CNS and PNS Regeneration:

Answer 32

Extent of Regeneration: PNS allows better and longer-distance axon regeneration, while CNS regeneration is often more limited.

Inhibitory Factors in CNS: The CNS environment contains more inhibitory factors like glial scars that hinder axonal growth, unlike the PNS.

Schwann Cells vs. Oligodendrocytes: Schwann cells in the PNS support axonal regeneration more effectively than oligodendrocytes in the CNS.

Question 33

What triggers astrogliosis in the brain?

Answer 33

Triggered by brain damage or immune response that disrupts the BBB, leading to the activation and proliferation of astrocytes.

Question 34

What is the outcome of astrocytes becoming reactive?

Answer 34

Reactive astrocytes increase in number and form a scaffold that can lead to the development of a glial scar in the brain.

Question 35

How does BBB disruption affect immune cell movement?

Answer 35

Disruption allows immune cells such as neutrophils and monocytes to enter the brain, where they release pro-inflammatory cytokines.

Question 36

What is the role of cytokines in neuroinflammation?

Answer 36

The role of cytokines in neuroinflammation involves activating microglia and astrocytes, which triggers inflammation and the formation of glial scars, potentially impeding neuronal survival and repair.

Question 37

What is the role of the stem cell niche near the ventricles in non-mammalian vertebrates?

Answer 37

The stem cell niche near the ventricles in non-mammalian vertebrates supports the growth and division of neuronal precursor cells, which can either produce more precursors or migrating neuroblasts that head to the brainstem motor area.

Question 38

SA: Why does a peripheral nerve regenerate better if it is crushed than if it is cut?

Answer 38

After being crushed, the damaged axon does not degenerate completely; complete degeneration occurs after being severed. When portions of the axon are still present, they provide
a guide for the regenerating axon to follow

Question 39

SA: In what ways does regeneration of nerves in the periphery recapitulate the initial development
of nerves

Answer 39

Nerve regeneration in the periphery mirrors initial nerve development by reactivating growth pathways and molecular mechanisms that guide axon growth and target reinnervation.

Question 40

SA: Why do axons regenerate so much more successfully in the PNS than the CNS?

Answer 40

1. Injury within the CNS often initiates cascades that result in necrosis or apoptosis of the
   damaged neurons and nearby neurons.
2. Additionally, unlike in the PNS, mechanisms do not exist in the CNS to reestablish a development-like environment, with glial cells actively inhibit growth of the CNS axons

Question 41

SA: What is apoptosis? What kinds of stimuli trigger apoptosis?

Answer 41

Programmed Cell Death
Stimuli including DNA damage, hypoxia, stress,and growth factor withdrawal can lead to excitotoxicity caused by elevated glutamate levels or activation of cytokine receptors .These mechanisms then lead to cellular changes that result in cell death.

Question 42

SA: In what ways do glia participate in repair and regeneration in the nervous system?

Answer 42

Schwann cells in the peripheral system help axonal regrowth by producing guiding molecules and growth factors, while in the central system, glial cells inhibit axonal regrowth and form a barrier called a glial scar to protect nearby cells from inflammation.

Question 43

SA: What is a transit amplifying cell?

Answer 43

A transit amplifying cell, derived from a neural stem cell, divides to produce neurons and glia but has a limited number of divisions unlike stem cells.