Lecture 8 Flashcards
what are the two routes of cerebral blood supply and what supplies them
- anterior / posterior cerebral
2. vertebral artery and ICA
Describe the route of the anterior cerebral artery
extends forwards and upwards from the ICA
Describe the middle cerebral artery
largest branch of the ICA
where does the posterior cerebral artery stem from
basilar artery
what does the ACA supply
Frontal lobe
what does the MCA supply
portion of frontal lobe and lateral region of parietal and temporal lobe
what does the PCA supply?
temporal and occipital lobe
what is the rate of cerebral blood flow?
constant
to allow neural activity not be compromised
what is the role of the ANS on cerebral blood flow?
very small –>global / acute / protective effect
SNS does’nt affect intracerebral pressure
can brain cells store energy?
no, they must be supplied with oxygen and glucose at the rate at which they expend energy
what percentage of cardiac output is supplied to the brain?
20%
what factors protect the brain’s blood supply?
- metabolic factors
- cerebrovascular autoregulation
- endothelial function
- BBB
what do astrocytes do?
important role in coupling blood flow and neural activity
-superimposed between neurons and blood vessels
what 3 things form the microvascular bundle?
- neurone
- astrocyte
- microvessel
role of astrocytes in neurovascular coupling?
astrocytes transmit chemical messages causing the cerebral vessels to constrict or dilate in relation to neural activity
How does neurovascular coupling works?
Astrocytes respond to signals released from neurons
- Neurons release glutamate
- Glutamate acts on NMDA / mGluRs receptors on astrocytes
- This produces Ca2+ spikes
- Which leads to the release of vasoconstrictor / dilator substances such as prostaglandins / arachadronic acid
What is hyperaemia?
an excess of blood in the vessels supplying an organ or other part of the body.
What is the role of NO?
vasodilator
cerebral vessels causes relaxation of vascular smooth muscle in the arterioles supplying cerebral microvessels
what does NO released by?
neurons and endothelial cells to dilate blood vessels
when is endothelial NO released?
in response to Ach released by cholinergic neurons
When is neuronal NO released?
co-released from interneurons with NPY
What is NPY
a powerful vasoconstrictor
what does chronically increased pressure do to the brain?
overwhelms the cerebral regulatory mechanism and cerebral perfusion pressure rises
What causes cerebral artery obstruction?
- deposition of atherosclerotic plaques
- Increase in wall thickness by inflammatory process and oxidative stress leading to hypertrophic remodelling of smooth muscle cells in response to increased pressure
Describe the steps in neurodegeneration
- remodelling causes disurption of BBB
- vessel leakage
- toxic products enter the brain parenchyma
- e.g amyloid B in alzheimers
describe the steps in a stroke occurring ?
- reduced CBF
- CBF no longer matches neural activity
- focal ischaemia
- stroke
What are the three types of stroke?
Ischaemic - 85% of cases - lack of oxygen supply to an area
Haemorrhagic - 15% of cases - rupture of blood vessel causing bleeding
TIA- mini stroke - symptoms dissappear after 48hr
what is thrombolysis?
clot breaking treatment using tPA
restores blood flow in ischaemic stroke
what are the limitations of thrombolysis?
- must be treated within 4.5hr
- must have a CT scan to rule out haemorrhagic stroke
- patients may not response and 5% can have haemorrhagic stroke
What is neuroprotection
drugs with interfere with the ischaemic casade
no clinical use so far
What are the 3 severities of the ischaemic casade
- autoregulation
- TIA with recovery
- permanent damage
What are the main events in autoregulation?
- Ischaemia –> loss of glucose and oxygen supply + build up of C02 / lactic acid
- Failure of membrane pumps ( Na+ K+ ATPases) leads to oedema and failure of glutamate reuptake
What are the main events that occur in TIA with recovery?
- disrupted membrane action potentials –> consistent action potential firing
- build up of glutamate causes overexcitation of glutamate receptors
what are the main events that occur in permanent stroke damage?
- Ca 2+ influx into cells and activates intracellular enzyme systems
- breakdown of cellular structure and free radical production
- apoptosis and necrosis
what are the role of pericytes in BBB dysfunction?
regulate the movement of substances between lumen of cerebral blood vessels and cerebral interstitial space
What happens to pericytes during disease
damaged by inflammatory cytokines in diseases affecting CNS such Alzheimers/ stroke / ALS / AIDS
BBB becomes leaky
what is the role of pericytes in health?
release molecules to brain endothelial cells in order to maintain the BBB integrity. Pericytes also secure normal perfusion and vasoregulation
What happens when pericytes are loss?
With pericyte loss, vessels regress and loose their vasoreactivity, leading to hypoperfusion and hypoxia. The BBB breaks down, resulting in leakage of neurotoxic substances leading to neuronal damage
What is the role of white matter?
50% of brain volume
transmit signals from one half of the cerebrum to another and lower brain centers
What is white matter made from?
mostly glial cells
axons –> myelinated and unmyelinated
bloods vessels
what are the causes of white matter ischaemia
- stroke / cardiac arrest
- neurodegnerative diseases
- Periventricular leukomalacia
what are oligodendrocytes
myelin-forming cells of the CNS
-most susceptible parts of white matter to ishaemic injury
role of cerebral white matter changes
major role with the onset of alzhiemers
PVL pathogenesis in neonates
- loss of immature and fully differentiated neonates
- myelin disturbances
What is PVL
The most common form of white matter damage in human neonates and often results in neonatal death
key features of PVL
5-10% of surviving premature infants develop cerebral palsy (a condition that affects muscle control and movement)
Also associated with intellectual impairment or visual disturbances.
Much more common in premature infants than in full-term infants.
White matter damage is due to changes in blood flow to areas around the ventricles which contain nerves affecting motor control.
