Glial Cells and Spinal Cord Injury Flashcards

1
Q

What are glial cells?

A

Cells surrounding neurons.

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2
Q

What are the functions of glial cells?

A
Myelinate (insulate sheath)
Physical and nutrional support. 
Regulate chemical and ionic content 
Remove debris
Form blood brain barrier
Regulate neurotransmitters.
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3
Q

What do neurons do?

A

Receive, conduct and transmit signals.

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4
Q

What are the methods currently use to study spinal cord injury repair?

A

Cell transplantation and the olfactory system.

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5
Q

What are the current clinical strategies for treating spinal cord injury?

A

Drugs during the acute injury phase (promote survival)
Advanced rehabilitation strategies
Neural prosthesis (electrical stimulation)

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6
Q

What is a major barrier to treating spinal cord injury?

A

The glial scar - it creates a physical and biochemical barrier to axonal outgrowth.

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7
Q

What are the current repair strategies for spinal cord injuries?

A

Fill any cysts/damaged tissue.
Prevent secondary damage and maintain glial/neuronal survival.
Promote axonal regeneration through scar to its target, limit scar formation.
Align axons, myelinate axons, make functional reconnections.

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8
Q

What are the reasons for failure of axonal regeneration?

A

Absence of a permissive substrate due to cavitation.
Presence of inhibitory molecules associated with damaged myelin.
Presence of inhibitory molecules associated with the glial scar.
Lack of neurotrophic stimulation.
Limited intrinsic growth capacity in mature CNS neurons.

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9
Q

Which cells could be used as a potential therapy for spinal cord injury?

A

Primary cells - schwann cells
Olfactory ensheathing cells.
Stem cells e.g. mesenchymal stem cells, ES cells, ES cell-derived
Induced pluripotent stem cells

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10
Q

Describe the research being undertaken on cell transplantation.

A

Rat olfactory system is one of the only CNS tissues that can continually support axonal outgrowth throughout life.

The adult rat olfactory receptor neurons can continually be replaced throughout life from stem cells in the epithelium.

Support for new axonal outgrowth is thought to be in part due to the glial cells that reside in the olfactory bulb termed olfactory ensheathing cells which may present a conduit for regeneration axons.

The olfactory system may be a more complex tissue with cellular interactions from other cell types.

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11
Q

Why are olfactory ensheathing cells (OECs) advantageous over other similar glial cells?

A

Ability to promote nerves to grow
Myelination/insulation of nerves so they signal properly
Interact with astrocytes forming the scar/breaking the barrier.

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12
Q

What are the similarities between OECs and Schwann cells?

A
Antigenic and morphological phenotype are very similar. 
Similar growth factor response.
May have HRG receptor differences.
Similar connexin profiles. 
Similar transcriptional regulation. 
Originate from the neural crest. 
Myelinate with Po.
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13
Q

What are the advantages of Schwann cells over OECs for CNS repair?

A

More accessible.

Can support regeneration, myelinate with Po

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14
Q

What are the limitations of using Schwann cells for CNS repair?

A

Poor Schwann cell migration in CNS.
Poor interaction with astrocytes in vitro.
Re-myelination limited to astrocyte-free areas.

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15
Q

What are the most numerous cell type in the CNS?

A

Astrocytes.

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16
Q

What is the astrocyte stress response upon injury?

A

Proliferation
Hypertrophy and enlarge
Upregulation of genes
Expression of inhibitory molecules.

(These are components of the glial scar which prevent regeneration)

17
Q

What do Schwann cells do that OECs don’t?

A

Secrete a factor (SCM) that:

Induces boundary formation in OEC/As confrontation assays
Increases astrocyte area and GFAP expression
SCM and OEC contact is necessary for induction of these characteristics of astrocytosis.
Inhibit CNS myelination.

18
Q

What is the problem with the model organism in studying OECs?

A

Rats use their smell to a greater extent than humans, olfactory cells may not work so well in humans.

19
Q

Have treatments of SCI with OECs been tested in humans?

A

Yes, early studies suggest they can create some improvement, regardless of age.

Further study will be needed into the long term outcomes.

20
Q

Which other clinical methods have found to have positive effects for spinal cord injury?

A

Electrical stimulation and locomotor training.
Physiotherapy
Pharmalogical approaches to target neuronal outgrowth inhibition and the scar.

21
Q

What is the pathology of a spinal cord injury?

A

Some myelin sheath broken.
Astrocytes build up.
Fluid filled cysts.