The rate of metabolism of the brain is amongst the highest of all organs in the body. Aerobic metabolism provides for all the essential brain functions, and a good supply of oxygen is essential for normal brain function. The arterial blood supply to the brain is the source of oxygen and glucose, and if the blood supply is compromised (ischaemia), then brain tissue can be destroyed.
The Monro-Kellie Doctrine describes the fact that the volume of the skull is constant and the consquences of intracranial tumours or haematomas on intracranial pressure.
Blood flow to the brain is fairly constant over a wide range of arterial pressures, a consequence of Autoregulation.
Blood flow to the brain is not evenly distributed, but is actively directed to highly active sites in the brain. This redisribution of blood flow according to neuronal needs can be analysed using fNMR and PET scanning.
Increased local blood flow is partly the result of accumulation of carbon dioxide in active tissues; carbon dioxide is a powerful vasodilator in the cerebral circulation. There is also evidence that astrocytes can influence local blood flow through the release of vasoactive compounds.
Image source: Clinicalgate.com
The Monro-Kellie doctrine states that the skull has a constant volume. Therefore there is less space for blood and CSF, which get squeezed out of the skull by an expanding intra-cranial mass.
Circulation in the Brain: Monro-Kellie Doctrine
The delicate structure of the brain is protected from our external environment by the skull. This is a hard and bony structure which cannot expand, and offers protection for the delicate structure of the brain.
The Monro-Kellie doctrine states that the volume of the skull is constant, and any new mass developing within the skull displaces CSF and venous blood, which compromise the oxygenation of the tissues.
If the brain becomes swollen (e.g. because of cerebral oedema, tumours, haemorrhage), pressure rises within the skull because it has a fixed volume. CSF pressure rises and the cerebral vessels, especially the veins, are compressed, and blood flow becomes compromised.
The reduction in cerebral blood flow is highly significant because the rate of metabolism of the brain is high, and the brain's metabolism requires oxygen. If blood flow is compromised the metabolic needs of the tissue are not satisfied and brain swelling (oedema and other types of damage) can occur.
This can easily lead to a vicious circle: increased swelling -> increased pressure -> reduced blood flow -> more ischemia (=lack of blood) -> more damage to the tissue and the blood capillaries -> more swelling - > etc -> etc. THis vicious circle leads to unconsciousness and death because the brain becomes starved of oxygen.
Monitoring the level of consciousness is vital in this situation and a medically induced coma may be used to reduce brain activity and metabolism. Drugs such as anaesthetics and sedatives can be used to induce unconsciousness and reduce cerebral metabolism. This also reduces the accumulation of interstitial fluid within the brain - and therefore the cause of tissue swelling. It enables the doctors to break the vicious circle.
Image source: Continuing Medical Education
Cerebral blood flow is fairly constant over a wide range of arterial blood pressures.
Blood flow to the brain is unaffected by changes in arterial blood pressures within a wide range (60 to 150 mm Hg), because of autoregulation.
Autoregulation may be due to the intrinsic properties of vascular smooth muscle. The myogenic hypothesis states that when the pressure in the blood pressure increases, the vessel wall is stretched, and the vascular smooth muscle contracts in response to the stretch.
The diameter of pial vessels is affected by changes in pCO2 and pO2.
High pCO2 causes cerebral vasodilatation, and CO2 is an important factor linking local blood flow to the metabolic activity of the neurones.
The relationship between increased metabolic activity and vasodilatation, mediated by CO2, affects capillary pressures, and therefore the production of interstitial fluids.
Medically-induced artifical coma is used to avoid cerebral swelling; drugs are used to reduce neuronal activity and therefore metabolism, and reducing cerebral blood flow.
Hyperoxia and hypocapnia reduce cerebral blood flow.
Image source: www.indiana.edu
More recently, PET and fMRI scanning methods have been developed to show brain function non- invasively. They measure blood flow in the brain, which changes very quickly as activity in an area of the brain increases or decreases. For example, many studies using these methods have showed that different parts of the brain are activated during different psychological actions. The figure shows PET scans as horizontal slices through the cerebral hemispheres (top of each slice is the front of the brain) taken under different levels of visual stimulation. Note the increasing dark red areas (which stands for increasing activity) at the back of the brain where the primary visual areas are located.(from http://www.indiana.edu/~p1013447/dictionary/imaging.htm)
Regulation of Local Blood Flow in the Cerebral Hemispheres
The Munro-Kelly Doctrine deals with the constancy of the sum of the brain and CSF volumes, being equal to the volume of the skull, which cannot expand.
The skull contains the volume of brain tissue + the volume of blood in the venous sinuses + the CSF volume, and the last two of these fall when intracranial pressure is raised. Elevation of CSF pressure as a result of a swelling of the brain or because of some 'space-occupying lesion' compresses the venous system, raising venous pressure and causing increased filtration in brain capillaries.
It is important to recognise this vicious circle, because it is the cause of gradual deterioration in brain function. Papilloedema is an important sign of raised CSF pressure; tissue swelling and venous obstruction are evident in this condition.
However, it is known however that the blood FLOW (volume/minute) to the brain tissue can change, and that the diameter of small vessels below the pia mater can change, and regulate LOCAL blood flow
Local blood flow is largely determined by the metabolic rate of neurones in that area:
Voluntary movements cause a rise in blood flow in the motor cortex, and visual stimuli increase blood flow in the visual cortex.
Patients with epileptic siezures similarly have an increase in blood flow in the neurones involved.
Carbon dioxide, produced by active neurones, is a powerful vasodilator.
Proposed mechanism for astrocyte-mediated coupling of synaptic activity to local vasodilation.
Synaptic glutamate release activates postsynaptic neuronal ionotropic glutamate receptors (GluRs) and astrocytic metabotropic receptors (mGluRs). Activation of mGluRs induces a transient increase in intracellular Ca2+, which propagates throughout the astrocyte and to its endfoot. The Ca2+ increase elicits production of arachidonic acid (AA) from phosphatidylinositol (PI), most likely by activation of phospholipase A2 (PLA2). The action of cyclooxygenase (COX) produces prostanoid products that cause vasodilation, and agents such as aspirin or indomethacin can block this COX action.
Astrocytes and the Regulation of Local Blood Flow
Astrocytes and Local Blood Flow within the Brain
Astrocytes have close contacts with neurones and with local blood vessels, and form a cellular network that can link neuronal activity and vascular reactivity. Astrocytes are linked by gap junctions, so when calcium ion levels increase within a group of astrocytes the message can be shared
Glutamate receptors on astrocytes cause increases in intracellular calcium concentration in astrocytes.
There is recent evidence that increases in calcium concentration in astrocytes cause vasodilatation in adjacent blood vessels after a short period (1-2 seconds). It is likely that astrocytes can release local mediators of this response. Prostanoids are thought to be involved as the response is blocked by non-steroidal anti-inflammatory agents.
Magnetic Resonance Imaging
Recent advances in imaging techniques allow radiologists to monitor local blood flow (fMRI) and metabolism (PET scanning). These are powerful techniques that have changed our understanding of the brain.