Cerebral Palsy Flashcards
What is the current definition of Cerebral Palsy?
Cerebral palsy describes a group of disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing foetal or infant brain.
The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, cognition, perception, and/or behaviour, and/or a seizure disorder
What are the sub-types of cerebral palsy?
Spastic (70%) - stiffness of affected muscles
Athetoid (20%) - dyskinesa of limb and facial muscles, resulting in involuntary movement
Ataxic (10%) - loss of balance and fine motor control
Some are a mix of all of these subtypes
Describe the findings of the Mutch report
The report was conducted in Scotland and published in 1992. It highlighted that potential risk factors for the condition were twin birth, low birth weight and premature birth
Later studies also indicated maternal malnutrition and infection can contribute to the disease development
Describe the Chick Embryo Model produced by Camm et al
A chick embryo (within an egg) is a useful model to replicate cerebral palsy as:
Hypoxia can be induced by wrapping in cling film, reducing oxygen in envoiroment
Infection can be injected
Albumin can be removed to cause malnutrition
Camm et al subjected chick embryos to hypoxia by wrapping in cling film, embryos were subjected to either 4 or 8 day hypoxia. Both showed a significantly lower birth weight and post natal weight gain
Cognitive test - During training, a red and blue bead was presented to the chicks. During testing, a red bead was coated with a chemical adversant and a normal blue bead; and presented to the chicks. The ratio of blue to red beads chosen showed the 4 day hypoxic chicks had memory impairments for 60 mins after training, whereas the 8 day hypoxic chicks had impairments from the beginning.
Describe the tests by Wang et al on chick embryos
Wang et al subjected embryos to acute hypoxia (1,2,4,8% O2) for 1 hour in day 19, and transfected with either Salmonela or E. Coli.
Salmonella increased mortaility with increased dose, hypoxia increased mortaility with decreased O2 levels. The two of them together , showed to work in synchrony, with the two working together totalling higher than any individually.
How does hypoxia cause cerebral degeneration?
Hypoxia (and infection) increase astrocyte and microglial response
Giusti et al showed that hypoxia increased mitochondrial NOS. General and selective NOS inhibitors were then introduced prior to hypoxia, which reduced hypoxia damaged neurones, identifying a potential therapeutic targets for cerebral palsy in humans
What models for cerebral palsy are being looked at to understand the human condition?
Monkeys (Myers)
Piglets (Martin et al) (Thoresen et al)
Rabbits (Tan et al)
In vitro (Oka et al)
How has the monkey model of cerebral palsy contributed to the understanding of the human condition?
Myers combined umbilical cord clamping with respiration obstruction to produce ‘acute total asphyxia’. This caused injury to the thalamus and brainstem
He then created prolonged partial asphyxia by partial placental ablation, which caused damage to the cerebral cortex.
MRI studies of human term infants show that the monkey response is similar to that seen in humans, proving a potential model to research how hypoxia causes brain injury.
How has the piglet model of cerebral palsy contributed to the understanding of the human condition?
Martin et al reported a model of asphyxia in 1-week old piglets with a 4-day survival period. This is an important model as it produced injury to the basal ganglia, thalamus and sensorimotor cortex. The pattern of injury closely resembles the pattern produced by near-total asphyxia in human term infants
Thoresen et al showed using piglets that brain cooling and its interaction with anaesthetic has substantial protective effects to reduce death and severe disability. This research stimulated research into head and full body cooling in infants, showing it to be a potential future treatment method.
However, these models produce a lack of chronic disability resembling cerebral palsy.
How has the rabbit model of cerebral palsy contributed to the understanding of the human condition?
Tan et al induced intrauterine asphyxia in rabbits which produced persistent hypertonia and motor deficits that resemble cerebral palsy.
However, the neuropathological changes in this model are less dramatic than the behavioural changes.
How has the in vitro model of cerebral palsy contributed to the understanding of the human condition?
Research into periventricular white-matter injury by Oka et al showed pre-oligodendrocytes are more vunerable to glutamate and free radical stress than mature oligodendrocytes.
This window of vulnerability corresponds to similar developmental stages of vulnerability seen in human infants.
