Fetal Brain Development and Brain Injury Flashcards
1
Q
What do the terms altricial and precocial mean?
A
- Altricial: means immature in terms of motor and cognitive functions at birth e.g. humans
- Precocial: means mature in terms of motor and cognitive functions at birth e.g. sheep
2
Q
What are the basic steps in CNS development?
A
- Neurogenesis and gliogenesis
- Cell migration
- Formation and guidance of fibres
- Synaptogenesis
- Myelination
- Selective cell survival and death
3
Q
Describe in detail neurogenesis and gliogenesis:
A
- At the time of neural tube closure there is a single layer of columnar epithelial cells (derived from ectoderm) which make up the neuroepithelial cells
- These neuroepithelial stem cells give rise to all neurons and macroglial cells
- Neurons are ‘born’ in the ventricular zone of the developing brain
- Early during this process the anterior section of the neural tube divides into 3 main structures: forebrain, midbrain and hindbrain
4
Q
Describe in detail neuronal migration:
A
- After proliferation, young neurons must migrate to their definitive locations, which informs their function
- In the cortex supporting cells known as radial glia form a specialised scaffolding to allow the neurons to migrate from the ventricular zone to their final position
- Each new layer of neurons in the cortex forms on top of previous layers, forming a structure where the outer most layer is the newest generation of neurons
- The final location of neurons informs their final function and thus promotes their specific differentiation
5
Q
Describe the formation of neuronal fibres in detail:
A
- Having reached their destination, young neurons must make connections with target cells
- This occurs via a process of axonal outgrowth which begins with a projection known as a neurite extending from the soma
- At the end of each neurite is a growth cone which forms a primitive dendrite structure with finger like projections known as filopedia which select target cells for interactions
- The guidance of these extending axons occurs via inhibitory or stimulatory signals which may be mechanical, electrical, or signals of differential adhesiveness- the filopedia will determine and follow the path of preferential adhesion (often mediated by NCAMs)
6
Q
Describe the formation of synpatogenesis in detail:
A
- As the filopedia of a neuron begins to make contact with target cells there is a cessation of axonal elongation
- One filopedia will broaden and develop specific features and projections
- The projections contact the target cell and communicate leading to signalling between the neuron and its target cell and the formation of a synapse
- Significant axonal branching occurs in the months-years following birth
7
Q
Describe myelination in detail:
A
- Myelin is formed by oligodendrocyte cells in the CNS
- Myelination begins after a period of oligodendrocyte proliferation and migration
- In the human brain myelination begins at appox 20 weeks gestation and continues for at least 2 years post-natally
- Only mature oligodendrocytes are able to effectively myelinate axons and these do not appear in the human brain until 30 weeks of gestation
- Oligodendrocytes are very susceptible to injury from the effects of hypoxia, inflammation and oxidative stress- all of which commonly occur in the event of preterm birth of asphyxia
8
Q
Explain how cell death and survival is regulated in CNS development:
A
- Approximately 50% of neuronal cells produced die around the time of synaptogenesis
- The purpose of this controlled cell death is to match the number of innervating populations with the capacity of target cells and to correct errors of cell migration and axonal projection
- Specific neurotrophic factors can act via receptors to enhance the survival of neurons
9
Q
Give a basic overview of the order of developmental events in the human brain:
A
- The neural tube is closed very early on in gestation
- Neurogenesis begins early in gestation and is generally complete by month 6-9 of gestation
- Early gliogenesis takes place in the first 4 months of gestation to establish the population of radial glial cells needed to act as a scaffold for neuronal migration
- neuronal migration occurs between months 4-9 of gestation
- Myelination first occurs at week 20 of gestation and increases in efficiency after 3 weeks of gestation and the bulk of this process occurs after birth (up to 2 years)
10
Q
What factors are required for optimal development of the brain?
A
- Adequate nutrition
- Adequate oxygenation
- Hormonal and growth factor support e.g. IGF-1 and glucocorticoids
- Sensory stimulation and activity
- Absence of toxins e.g. alcohol
11
Q
What is a neural tube defect?
A
- Neural tube defects are defects in the closure of the neural tube (which occurs between day 22-28)
- The defect in closure can have a variety of outcomes, if the defect is anterior it can result in anencephaly and if it is posterior it can result in spina bifida
- The cause can be genetic, nutritional or drug related- many cases have been linked to folate deficiency
12
Q
What is fetal alcohol syndrome?
A
- Alcohol readily diffuses across the placenta and disrupts radial glia and astrocytes therefore altering neuronal migration and survival
- Alcohol also increases the susceptibility of cells to free radical damage which induces cell death
- Heavy alcohol exposure in utero leads to FAS
- FAS presents as a pattern of defects characterised by facial abnormalities, growth restriction and it the leading known cause of preventable mental retardation
- FAS causes a decrease in brain size, decrease in basal ganglia and cerebellum size and an impaired corpus collosum
13
Q
What is cerebral palsy?
A
- CP is a term that describes an abnormality of movement or posture
- CP is the result of a lesion known as a periventricular leukomalacia which occur during brain development
- The injury is non-progressive and affects the white matter of the brain as the causes of CP: IUGR, intrauterine infection, preterm birth and birth asphyxia all occur during the second half of gestation during white matter development
14
Q
How does preterm birth cause perinatal brain injury?
A
- Significant brain development occurs during the final period of gestation
- The risk of developing CP is greatly increased in preterm babies
- There are confounding factors such as IUGR and infection, which are both causes of perinatal brain injury and preterm birth- hence the need for animal models to isolate and study the effects of preterm birth
15
Q
How does infection during pregnancy cause perinatal brain injury?
A
- Viral infections, chorioamnionitis or intrauterine infection are all well known risk factors for CP
- These infections produce a strong feto-placental inflammatory response and upregulate pro-inflammatory cytokines which can access the fetal brain
- Antibiotics may prolong a pregnancy however studies show these infants have a higher incidence of CP
- Other treatments being trialled include anti-inflammatory drugs and umbilical cord blood stem cells
