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neurodegenerative diseases > Regenerative therapies > Flashcards

Regenerative therapies Flashcards

1
Q

what are some future treatments in comabtting myelin debris?

A
  • Anti-Nogo A antibodies increase axon regeneration in rat spinal cord injury (further away they moved from lesion )
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2
Q

what do Anti-Nogo antibodies do in non-human primate SCI?

A

increase functional recovery and sprouting is seen
( it is currently in phase 2 looking at positive effects of recovery)

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3
Q

Explain NogoA knockout experiments?

A

knockouts have produced variable amounts of axon regeneration after injury.
- one knockout regenerates vigorously
- one regenerates a bit
- one doesn’t regenerate at all

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4
Q

what does a triple knockout of NogoA, MAG and OMgp show?

A

no regeneration after injury

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5
Q

what are the main functions of (IN A NORMAL CNS):
- microglia
- astrocytes
- oligodendrocytes

A

microglia: immune surveillance
astrocytes: neuronal support
oligodendrocytes: continually cycling population

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6
Q

what are the major markers/ molecules produced (IN A NORMAL CNS) by :
- microglia
- astrocytes
- oligodendrocytes

A

microglia: CR3, MCSF and TGFB1
astrocytes: GFAP, CAMs, NGF, FGFs, CNTF, TGFB1
oligodendrocytes: PDGFaR

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7
Q

what CS-PGs are expressed (IN A NORMAL CNS) by:
- microglia
- astrocytes
- oligodendrocytes

A

microglia: none known
astrocytes: Brevican, versican, phosphacan
oligodendrocytes: NG2, versican

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8
Q

What happens to glial cells in an injured CNS?

A

All cells become hyperactive

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9
Q

What does an injured CNS do to microglia?

A

Increases in markers (CR3, MCSF, TGFB1)
New molecules produced: TNFa, IL-1b, IL-6, B7, MHC-I, CAMs, MCSF-R, integrins
Function: antigen recognition, proliferation, hypertrophy

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10
Q

what does an injured CNS do to astrocytes?

A

Increases in markers (GFAP, CAMs, NGF, FGFs, CNTF, TGFB1)
New molecules produced: TNFa, IL-1, IL-6, tenascin
Function: Scar formation, hypertrophy
Increases in CS-PGs expressed (Brevican, versican, phosphacan)

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11
Q

what does an injured CNS do to oligodendrocyte precursor cell?

A

Function: Rapid proliferation, hypertrophy
Increases in expressed CS-PGs (NG2, versican)
Molecules produced: PDGFaR

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12
Q

what is Chondroitinase ABC (cABC) ?

A

an enzyme that digests glycosaminoglycan side chains of CSPGs

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13
Q

describe how you can combat glial scar with cABC?

A
  • after rodent spinal cord injury and digestion of glucosaminoglycan side chains with cABC
  • no CSPG immunoreactivity detected
  • fibres regrew around lesion site better than untreated
  • cABC showed more fibres going around the lesion area
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14
Q

what is a potential problem of cABC?

A

regrowth following treatment follows to areas where there is digestion of CSPGs

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15
Q

what current treatment could cABC enhance?

A

rehabilitation

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16
Q

how can cABC enhance rehabilitation?

A

specific forelimb reaching rehabilitation with cABC leads to a dramtic recovery of skilled forelimb function, even with a chronic injury

17
Q

what two experiments are done with rodents to test cABC with rehabilitation ?

A
  • rat trained to reacg for a sugar pellet through a glass window
  • staircase task with a sugar pellet on each step
18
Q

what did a combined treatment of cABC and rehabilitation lead to?

A

a large amount of recovered axons
- improved forepaw reaching
- axonal growth up to 5mm caudal to lesion site

19
Q

within regeneration and repair what five things could cell transplants provide?

A

1) bridge over/ through scar
2) permissive substrate
3) cell replacement
4) growth factors
5) remyelination

20
Q

name the three common transplant types ?

A

1) schwann cells
2) olfactory ensheathing cells
3) Stem cells (induced pluripotent, embryonic, multipotent progenitors)

21
Q

Why are olfactory ensheathing cells potential for cell transplants?

A
  • similar to schwann cells
  • constantly turned over
  • protect olfactory cells
  • has regenerative functoion so may help with CNS
22
Q

how does cell transplantation work in parkinson’s disease?

A
  • dissection of ventral mesencephalic tissue (1-8 donor embryos used as a source of tissue)
  • transplant preparation (fresh or hibernated tissue is homogenised into cell suspension or small tissue piecec)
  • grafting procedure (stereotactic injection in caudate and/ or putamen, 3-8 injection tracts per striatum)
  • Immunosuppression (Ciclosporin for 6 months or long-term triple drug therapy to prevent rejection)
23
Q

what the sequential pathway for schwann cell- like OEC?

A

precursor cell –> astrocyte like OEC –> Intermediate OEC –> Schwann cell-like OEC

24
Q

what can OECs do in regeneration and repair?

A
  • they provide trophic support (neurotrophins)
  • can phagocytose debris
  • allow cells and axons to integrate through glial scar-rich regions
25
Q

what stem cells are important with regeneration and repair?

A
  • embryonic
  • Induced Pluripotent (iPSC)
  • Mesenchymal stem cells
26
Q

what are NSCs?

A

Human Neural Stem Cells

27
Q

how many clinical trials are currently going on around the world using stem cells in SCI patients?

A

38

28
Q

what is the importance of biomaterials in repair?

A

1) Hydrogels that mimic the ECM
2) Provide physical or topographical cues for axonal growth
3) substrate for cell delivery and survival
4) important part of combined therapies (growth factors, cells, etc.)

29
Q

what are CPGs?

A

Central Pattern Generators - a neural circuit that can produce a rhythmic motor pattern in the absence of descending control: potentially without sensory input)

30
Q

What is epidural stimulation ?

A

uses electrical stimulation with propriospinal input derived from muscles, bones, and skin that project to the lower spinal cord (to serve as a source of neural control)

31
Q

For quadruped mammals where is it assumed the neural control of locomotion is based?

A

CPGs within the spinal cord

32
Q

what does the CPGs network generate?

A

the rhythm and shapes the pattern of bursts of motor neurons

33
Q

what does the rostral spinal cord network control?

A

forelimb movement

34
Q

what does the specialised neural circuits within the caudal spinal cord organise?

A

hindlimb locomotor activity

35
Q

what mediates the coordination of circuits within the caudal spinal cord and rostral spinal cord?

A

propriospinal neurons with long axons, which couple the cervical and lumbar enlargements of the spinal cord

36
Q

name five key things about propriospinal neurons?

A
  • contained entirely within the spinal cord
  • may have short segmental or multi-segmental projections
  • may convey supraspinal descending commands and aid in the integration of these commands with sensory feedback from the body
  • mediate and coordinate rhythmic motor output involving multiple joints and neurons across several spinal segments
  • they provide a large proportion of the excitatory and inhibitory inputs that the motor neurons recieve
37
Q

give an example of electrical stimulation with rehabilitation

A

weight-supported locomotor training and epidural stimulation resulted in walking with assistive devices

neurodegenerative diseases (11 decks)

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