Damage and Repair in the injured CNS Flashcards
name some CNS injuries
Spinal cord injury (SCI)
Traumatic brain injury (TBI)
(ages 15-24 most at risk for 2 above)
Strokes
Brain cancer
ALL HAVE SEVERE FUNCTIONAL CONSEQUENCES E.g. SPI –> paralysis
what happens when regular tissue is damaged?
Damage to non-nervous tissue will activate proliferation of existing cells in the tissue to replace the missing cells.
Complexity of the non-nervous tissue here is at the expense of the individual immortality of the cells.
Only the tissue structure and function need to be maintained, the cells can be replaced.
what is synaptic plasticity?
After the proliferation and migration of neuronal progenitors, the final step of neural differentiation is the formation of synaptic connections.
This results in neurones organising into complex networks.
Synaptic plasticity can occur
Synaptic plasticity: is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity.
In nervous tissue every neurone has a role to play.
Neurones are not replaceable by cell division.
By taking out one or two neurones we affect the whole function of the network
In the case of nervous tissue, the complexity of the structure is at the expense of reparability.
what is the structural organisation of the CNS?
Different parts of the brain have different functions.
Therefore, by looking at someone’s symptoms we will know what part of the brain is injured.
The same strictness reflects to the spinal cord.
We can determine the level of injury just by looking at the symptoms and signs of the injury.
At the spinal cord the loss of movement, sensation and autonomic control occurs below the level of the injured segment - the more cranial the lesion, the greater loss of function
what does consequence of injury depend on?
Consequences of an injury depend of the site and size of the injury but not on the type of injury (e.g. stroke, tumour etc.)
how does the brain get its energy supply?
how is this affected after a brain injury?
Brain is 2% of the total body mass
It consumes 15% of the energy generated in the body
It has no energy stores of its own (except small amount of glycogen in astrocytes)
Energy is derived exclusively from glucose metabolism that is provided by the blood supply.
If the blood supply is not perfect, the demand for energy and the supply for energy will become unbalanced
This will result in an energy crisis in the brain as there are no energy stores in the neurones.
how does a skull fracture cause brain injury?
Majority are from blunt force or penetrating trauma that in turn injure the brain matter
what is a cerebral haemorrhage?
what can cause a haemorrhage?
A cerebral haemorrhage is an intercranial bleed.
It results in massive destruction of brain tissue.
The ventricular system becomes filled with blood.
Blood covers the entire surface of the brain
Causes:
Hypertension can lead to massive cerebral haemorrhage.
Disease of the blood vessels of the brain.
E.g, Alzheimer: patients can get amyloid protein deposits in the wall of blood vessels which makes them brittle leading to a haemorrhage.
Arterio-venous malformations also cause haemorrhages.
The blood vessel walls don’t form well.
Therefore, blood does not flow properly which can cause an embolism, leading to a cerebral haemorrhage.
Aneurisms also lead to cerebral haemorrhages
what are lacunar infarcts?
Infarct: a small localised area of dead tissue resulting from failure of blood supply.
Where infarcts happen, the tissue dies away leaving a tiny fluid filled hole.
They occur usually due to untreated hypertension and can occur in diabetics.
At the time they happen they don’t cause massive functional disruption.
Tiny infarcts cause fainting.
However as they accumulate, they will eventually disrupt brain function leading to vascular dementia.
They usually accumulate in the white matter but can affect grey matter.
what would movement of the brain in the skull cause?
Initial impact can cause cerebral contusions (injured tissue where capillaries are ruptured) and lacerations
As a consequence of the impact, the brain moves inside the skull causing
Hematomas (epidural and subdural) –> raised intracranial pressure which cause compression of the brain and blood vessels
Hypoxic injury & focal ischaemic lesions
Contusions and diffuse axonal injury –> cause structural brain damage
what is the hypoxic – ischemic brain injury?
Hypoxia is a condition in which a region of the body is deprived of adequate oxygen supply at the tissue level
Ischaemia is a restriction in blood supply to tissues, causing a shortage of oxygen that is needed for cellular metabolism
The high energy requirement of the brain relies exclusively on glucose metabolism via the blood supply
Demand can be greater than supply if something interferes with the blood supply.
This results in an energy crisis.
This can occur via:
Drop in cerebral perfusion - If person suffers global ischemia (due to a cardiac arrest) or severe hypotension
CO poisoning - Hypoxia (lack of O2)
Hypoglycaemia
Severe anaemia (low RBC)
Generalized seizures - lead to contraction of blood vessels
describe anoxic neurones
Anoxic neurones = no oxygen supply
Different neurones have different sensitivities to hypoxia.
Ischemia lasting 4-5 minutes - irreversible damage to:
Hippocampal and neocortical pyramidal cells
Striatal Neurons
Purkinje cells
Longer lasting ischemia is required to cause irreversible damage in
Thalamic and brainstem neurons (more resistant)
image:
Normal (left)
Hypoxic injured brain (right) - see density of pyramidal neurones is reduced and they look very unhealthy.
Sometimes you can see blood cells to show blood leakage into brain.
what is laminar necrosis?
Laminar degeneration only affects outer layer of grey matter, these are the most sensitive neurones
Laminar necrosis – the death of cells in the cerebral cortex of the brain in a band like pattern.
Separation of upper (dead) and lower (alive) layers due to differential sensitivity of neurones.
the image in the question flashcard:
there’s a ribbon of cell death encasing the brain
the cell death can be so pronounced that you can see the top of the tissue sepereating from the lower levels of the cortex leading to the laminar necrosis
what happens following a hypoxic injury?
If an individual survives a hypoxic injury there are changes in tissue that occur:
1-2 days after: Swelling of anoxic neurones - these are destined to die.
Within 2 weeks: Necrosis and neovascularisation is complete and hypoxic tissue starts to revascularize - you can see blood vessels growing into the brain tissue
2 months: Hypoxic tissue is completely replaced by glial scar - massive tangle of proliferated glial cells.
what are mechanisms that contribute to damage to the brain?
The primary injury:
leads to tissue loss and tissue damage
Loss of neuronal connections leading to functional deficits
Breach of BBB
Secondary damage: Due to the body’s response to the primary damage, usually leads to more damage.
Hypoxia will illicit a glial response.
This will lead to the upregulation of inflammatory mediators in the brain.
These further enhance gliosis and infiltration of glial cells and can compound neuronal damage further.
Oedema may occur in the brain due to the breakdown of the blood brain barrier
This results in further compression of the brain tissue and blood vessels which leads to further hypoxia and neuronal loss.
Once acute phase is over, we will have development of long-term consequences:
After the acute phase there is some chance of repair in the nervous system.
This affected by different factors.
how does repair and regeneration occur in the PNS?
Axonal regeneration is present
Following the axonal injury macrophages clear away the debris and there is a growth process which allows regeneration of peripheral nerve
how does repair and regeneration occur in the CNS?
No axonal regeneration
The reasons for this are:
There are no macrophages in CNS that could clear away debris
There is also a lot of inhibitory molecules that develop from astrocytes that prevent regeneration in CNS (brain or spinal cord).
what are the features of CNS Injury?
The axons of the CNS do not lack the intrinsic capacity for regeneration.
They have that capacity but the inhibitory environment reduces their ability to regenerate:
Lack of neurotrophic stimulation
Neuronal Death
Demyelination
what is neuronal plasticity?
Neuroplasticity is depending on Neurotrophin synthesis and then its release into the CNS
Neurotrophin signalling affects:
presynaptic transmitter release
post synaptic responsiveness
membrane excitability.
synaptic morphology
Neurotrophin synthesis, secretion and signalling can be enhanced by neuronal activity.
This is what neuronal rehabilitation is trying to kick start and maintain in patients.
This is to maintain synaptic remodelling and neuronal plasticity to recover function after injury.
Structural plasticity takes longer in adult than new born baby (90 mins vs 90 days).
