Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neurobiology > Cerebral Palsy > Flashcards

Cerebral Palsy Flashcards

1
Q

Definition of cerebral palsy

A

A group of movement disorders characterised by dysfunction of movement or posture caused by insult to the cerebrum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the causes for hypoxia in the 2/3rd trimester?

A
  • Bleeding from the uterus
  • Impaired placental function
  • umbilical cord obstruction
  • compressed aorta (leading to less blood in uterine arteries)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Aorta

A

the main artery that carries blood away from the heart to the rest of the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Non-hypoxic causes of cerebral palsies

A
  • genetic mutations related to metabolism
  • environmental toxins such as mercury or alcohol
  • infections of the uterus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the incidence of cerebral palsy?

A

2-2.5 per 1,000 live births
(the most prevalent perinatal injury)

Survival is increasing due to success of newborn intensive care units

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

3rd trimester hypoxia

A

Characterised by injury (neuronal death, abnormal myelination, gliosis) to the striatum,
+ additional injury to other regions (Cortex/HPC) in 50% of cases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the pathological changes that occur in 3rd trimester hypoxia?

A

Neuronal death, gliosis, abnormal myelination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Gliosis

A

Increase in reactive astrocytes and microglia (Iba1+ve)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Other names for 3rd trimester hypoxia

A

Status marmoratus due to the marbled appearance of the striatum
+
Extrapyramidal/dyskinetic cerebral palsy due to extra-pyramidal damage causing movement deficits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Symptoms of 3-TH

A
  • dyskinesia
  • chorea
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

dyskinesia

A

difficulty executing voluntary movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

chorea

A

sudden, uncontrollable, jerky motions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

prevalence of 3-TH

A

accounts for 25% of cerebral palsies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Rice-Vannucci hypoxic-ischaemic model

A

Rats ligation of the unilateral common carotid artery following by exposure to hypoxic conditions

3-TH: PN7 rats exposed to 8% oxygen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

why rat post-natal day 7?

A

Resembles the developmental stage of the human brain in the 3rd trimester

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why is ligation used alongside oxygen deprivation in the Rice-Vannucci model?

A

Oxygen levels cannot be decreased below 8% as the animals stop breathing and die, so ligation of one of the common carotid arteries allows for brain damage without prevention of breathing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What aspects of human brain damage does the Rice-Vannucci model exhibit?

A
  • neuronal loss, primarily in the basal ganglia and secondarily in the cortex
  • increased gliosis
  • abnormal striatal myelination
  • locomotion problems
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Mechanism of 3-TH

A
  • Decreased oxygen
  • Decreased ATP
  • disruption of acid:base balance due to anaerobic respiration
  • disruption of ion homeostasis due to malfunctioning of ATP-dependent cation pump
    = greater Na+ influx
  • depolarisation, primarily in the glutaminergic neurons due to their excitable tendencies
  • excessive glutamate release
  • NMDA activation
  • excitotoxicity due to excessive calcium influx
  • activation of kinases/proteases and free radical generations
  • membrane disintegration
  • cell death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Neuroprotective treatments

A

aim to prevent the pathological cascades that cause cell death

eg: antioxidants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Neurorestorative treatments

A

aim to replace the dead neurons and restore damaged tissue through formation of new neurons

eg: stem cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Existing treatment for cerebral palsy

A

Therapy aimed at minimising movement issues
- physiotherapy, occupational therapy, surgery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Why was gentle hypothermia investigated as a treatment for 3-TH?

A

Evidence has shown that it decreases glutamate release, and free radical production, as well as inhibiting apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Mild hypothermia

A

a decrease from normal body temperature by 1-3°C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

moderate hypothermia

A

a decrease from normal temp by 4-7°C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

systemic hypothermia

A

cooling of the whole body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

selective hypothermia

A

cooling of the head

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Animal model/Clinical trials of gentle hypothermia for 3-TH show…

A
  • gentle hypothermia prevents neuronal death in animal models
  • moderate improvement in disability in humans
  • benefits in middle childhood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Why was antioxidants/gentle hypothermia investigated as a treatment for 3-TH?

A

Antioxidants act to scavenge free radicals, which was hypothesised to have an additive effect to the hypothermic decrease in free radical production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Animal model/Clinical trials of antioxidant + gentle hypothermia for 3-TH show…

A
  • long term neuroprotective effect that restored # of neurons to healthy levels in Rice-Vannucci model
  • functional restoration in performance on staircase test
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Staircase test

A

mouse is placed in box, and has to reach to sugar pellet that are placed on a staircase apparatus. # of pellets reached for/eaten is measured.

  • one of the best test for measuring motor skills after striatal injurt
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Why was Xenon/gentle hypothermia investigated as a treatment for 3-TH?

A

Xenon is a NMDA antagonist and an anaesthetic gas, thus may help mitigate hypoxic excitotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Animal model/Clinical trials of Xenon + gentle hypothermia for 3-TH show…

A
  • rescuing of normal motor skills at 7-9 weeks in Rice-Vannucci model
  • improvement in pathology in rats, but not = to healthy ctrls
  • no adverse effects but also no therapeutic effect shown in humans (potentially due to lag in treatment)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Caveat of Xenon treatment

A

It is expensive
(but can be recirculated to reduce costs)

34
Q

Why was Erythropoietin/gentle hypothermia investigated as a treatment for 3-TH?

A

Erythropoietin (EPO) is anti-excitotoxic, anti-oxidant, and anti-apoptotic

35
Q

Animal model/Clinical trials of Erythropoietin + gentle hypothermia for 3-TH show…

A
  • decreased extent of cerebral palsy in primate models
  • improves outcome in 12mo humans compared to just hypothermia
36
Q

Potential Neuroprotective Treatments for 3-TH

A
  • gentle hypothermia (standard of care)
    + Antioxidant
    + Xenon
    + Erythropoietin
37
Q

Stem cells

A

unspecialised cells that are able to divide and differentiate into specialised cells depending on the context

38
Q

Intrinsic sources of stem cells

A
  • the sub-ventricular zone
  • sub-granular zone of the hippocampus
39
Q

stem cells of the SVZ

A

typically migrate via the rostral-migratory stream (RMS) to the olfactory bulb where they differentiate to become olfactory neurons

40
Q

stem cells of the SGZ

A

form the neurons of the dentate gyrus

41
Q

Extrinsic sources of stem cells

A

embryonic stem cells are pluripotent and obtained from the inner cell mass of embryos

adult mesenchymal stem cells (MSCs) are multipotent, and are obtained from bone marrow (typically the femur)

adipose tissue - MSCs have 90% identical growth factor section to bone-marrow derived MSCs & are more effective at treating stroke

42
Q

Which stem cells show the most potential in treatment of 3-TH and why?

A

Bone marrow derived mesenchymal cells (MSNs) due to ease of collection (from self) and low chance of immune response

43
Q

Animal model/Clinical trials of stem cells for 3-TH show…

A
  • decreased lesion size and functional improvement on cylinder test following MSN treatment in rice-vannucci model
  • restored # SPNs to level healthy ctrl in Rice-Vannucci + trend towards functional improvement in cylinder test
44
Q

hypothesised mechanism underlying treatment of 3-TH with stem cells

A

sub-ventricular zone stem cells preferentially differentiate into striatal SPNs in the presence of MSCs due to growth factor release

45
Q

Stain used to identify dividing cells

A

BrdU

46
Q

Stain used to identify SPNs

A

DARPP

47
Q

2nd trimester hypoxia

A

characterised by FOCAL PERIVENTRICULAR LEUKOMALACIA which describes the preferential injury to the white matter near the lateral ventricles

48
Q

What are the pathological changes that occur in 2-TH

A
  • Death of oligodendrocytes
  • axonal injury

(grey matter is less affected in 3-TH; there is a loss of striatal volume but generally no cell death)
- 15% exhibit cell death in the cerebral cortex

49
Q

Symptoms of focal periventricular leukomania caused by 2-TH

A

spastic displegia: unco-ordinated contraction of the skeletal muscle in the legs due to damage to the leg region of the pyramidal tract

50
Q

what is the prevalence of 2-TH?

A

It accounts for ~40% of cerebral palsies

51
Q

Oligodendrocyte precursor/progenitor cell are defined by presence of…

A

A2B5

52
Q

What are the forms of oligodendrocyte in development?

A
  1. oligodendroglial precursor/progenitor cell
  2. pre-oligodendrocyte
  3. immature oligodendrocyte
  4. mature oligodendrocyte
53
Q

pre-oligodendrocytes are defined by presence of…

A

O4 (sulfatide)

54
Q

immature oligodendrocytes are defined by presence of…

A

O1

55
Q

Oligodendrocyte precursor/progenitor cell are defined by presence of…

A

MBP (myelin basic protein)

56
Q

What types of oligodendrocytes are present in the 2nd trimester?

A

pre-oligodendrocytes (O4+ve) abnd immature oligodendrocytes (O1+ve)

57
Q

What is the proposed mechanism underlying 2-TH?

A

Oligodendrocytes are extremely susceptible to glutaminergic excitotoxicity and free radical which occur in hypoxia.

58
Q

Expression pattern of glutamate receptors on oligodendrocytes

A

AMPA - soma
NMDA - processes

59
Q

Why rat post natal day 2?

A

Equivalent to human brain development in second trimester
- shown by dominant O4+ve staining, indicating a large proportion of pre-oligodendrocytes

60
Q

What treatments have been investigated for 2-TH

A
  1. memantine (NMDA antagonist)
  2. UDP glucose
  3. glial derived neurotrophic factor

(2&3 induce differentiation of SVZ NSPCs into oligodendrocytes)

61
Q

What evidence supports the use of memantine/UDPG/GDNF for 2-TH

A

All treatments were shown to decrease white matter pathology and reduce hind leg motor dysfunction in PN5 Rice-Vannucci model

62
Q

What factors are important when examining treatments for 2-TH

A
  • The use of PN2 rats in a Rice-Vannuci model
  • Measurement of O4 (pre-oligodendrocytes) positive cells
63
Q

Why should gentle hypothermia NOT be used for 2-TH?

A

Premature babies are ineffective at coping with changes in body temperature

64
Q

diffuse periventricular leukomalacia (PVL)

A

Mild injury to the white matter of the cerebrum caused by repeated insults of short duration during the second trimester

65
Q

What is the pathology of diffuse PVL?

A
  • oligodendrocyte death
  • axonal injury
  • long-lasting decreases in cerebral white matter & myelin
  • potential injury to dopamine neurons of the SNpc
  • loss of striatal and cortical volume (but no death of neurons)
66
Q

What are the symptoms of diffuse PVL?

A

ADHD & memory deficits

67
Q

What is the prevalence of diffuse PVL?

A

~1.2% of all live births, with increased representation in males

68
Q

What causes diffuse PVL?

A

Premature birth and repeated short duration hypoxic exposures due to underdeveloped control of breathing by brainstem neurons

69
Q

Animal model of diffuse PVL

A

14/15 min periods of exposure to 1.5% O2 every 2hours for three days (PN1-3)

70
Q

How does the animal model of diffuse PVL reflect the presentation in humans?

A

Animal models show
- decreased O4 (pre-oligodendrocytes) in the white matter
- decreased myelin surface area
- make slightly more error on the radial arm test for short term memory
- are hyperactive to delayed reward, but are NOT inattentive

71
Q

radial arm test for short term memory

A

A maze composed of 8 arms radiating from a centre point. Each arm contains a treat. The animal must remember where it has been (and which snacks it has eaten). Each incorrect entry is recorded.

72
Q

dopaminergic pathways innervating the cerebrum (2)

A
  1. mesolimbic (VTA-> cortex)
  2. nigrostriatal (SNpc -> striatum)
73
Q

dopaminergic pathway implicated in ADHD hyperactivity

A

mesolimbic, death of dopaminergic VTA neurons observed in rat model of diffuse PVL

74
Q

Why are different cell types affected by hypoxic damage in different trimesters?

A

The biochemistry differs between cells and regions throughout development causing different cell types of be more vulnerable to hypoxia.

75
Q

What contributes to the vulnerability of striatal SPNs in the 3rd trimester?

A

Have a high level of glutamate receptors comparative to other cells in the 3rd trimester, thus are more vulnerable to glutaminergic excitotoxicity

76
Q

What contributes to the vulnerability of oligodendrocytes/VTA dopamine neurons in the 2rd trimester?

A

low levels of antioxidant enzymes

77
Q

RMTg

A

rostromedial tegmental nucleus: provides GABAergic input to the dopaminergic neurons of the VTA

78
Q

Potential mechanism of cerebral hypodopaminergia in ADHD + evidence

A

Increased inhibition of dopaminergic VTA neurons by the RMTg
- transmission electron microscopy showed an increase in length and thickness of the post-synaptic density between RMTg & DA nRs of VTA

79
Q

Hypothesised mechanism of schizophrenia + evidence

A

Decreased inhibition from RMTg to dopaminergic VTA cells

decrease in volume of pre-synaptic terminals in RMTg
+
decreased in length and volume of post-synaptic density of RMTg GABA- VTA DA synapse

80
Q

The maternal immune activation model

A

based on the fact that immune activation in mothers is a risk factor for schizophrenia

Involves the injection of poly I:C at gestational day 15 in rats
- results in ‘schizophrenic’ offspring that show dopaminergic hyperfunction and response to anti-psychotics

Neurobiology (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions