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What are some primary considerations in regards to the location of the nervous system?

- protection - the nervous system is vital, and relatively fragile
- protection within an enclosed volume brings the danger of damage via pressure increase, inflammation and oedema
- brain cells have very high metabolic demands (fuel, gas exchange)


What are the coverings of the CNS?

The meninges:
- dura (tough)
- arachnoid (spidery)
- pia (close)

looks like a leathery bag around brain


What are the three layers of the meninges?

Dura mater: thick connective sheet tissue, outer most layer,

Arachnoid mater: connective tissue, mesodermal origin, except for a few places the arachnoid layer is adherent to the dura. Virtual space that under pathological conditions might fill up (or something). Gives off tendrils of connective tissue which joins up with pia layer. Space between is filled with cerebrospinal fluid. A lot of the major arteries in subarachnoid space.

Pia mater: close to the brain


What is cerebrospinal fluid?

Basically like blood plasma but without the proteins. This fluid surrounds the CNS - CNS essentially floating.

One function of the CSF is protection. It cushions the CNS from the effects of impacts/physical damage.
Provides a way for things to circulate. Because CSF is produced all the time there is actually a circulatory route for CSF and it might distribute endocrine type signals within the system.
It may have a sort of cleaning function: products that are made in the brain that are not being used/toxic might be able to find a way out of that environment and back into the venous system.
Important because the brain doesn't have a lymphatic system like every other tissue.

400-500ml produced daily.

CSF comes from the blood and is returned to the blood and that is how we maintain a constant volume.


What happens to the meninges at the midline?

The dura splits in half, leaving a space in the middle: venous sinus filled with venous blood.

Into that vein there is a communication between the CSF in the subarachnoid space and the venous blood. You can't add volume to an enclosed space. As much CSF is added as must be removed: done via granulations into venous sinus


What are the ventricles?

The ventricles are the sites where CSF accumulates and is produced.

Specialised tissue within these ventricles call the Choroid plexus are how/where CSF is produced.

The lateral ventricles follow the shape of the cerebral hemispheres. Each hemisphere has one lateral ventricle.

Modified capillaries run along the base of the lateral (and other) ventricles and obviously contain plasma. Aspects of plasma are taken from there and make up the CSF (mainly water and ions). Certainly none of the cells, proteins etc. It is really just like weakly ionic water. Produced in all four of the ventricles.

Midline third ventricle has a little hole where the two sides of the thalamus touch. A tunnel known as the cerebral aqueduct goes to the fourth ventricle which is in the brain stem.

Clinically it is very important to be aware of the ventricles, of the fluid they contain, where this fluid is going and the consequences of having fluid in a fixed volume/what can go wrong.
The ventricles are connected so CSF flows between them, gets to subarachnoid space via some passages in the fourth ventricle.
The passage continues on from the fourth ventricle --> no one really knows where the fluid goes. Just ends in a blind ended tube. However the cells lining this tube are ciliated so theorised that they beat and somehow stimulate movement of the CSF.


What are the two main distinctions of brain matter?

Grey matter: relatively soft, on the outside.

White matter: relatively hard, on the inside. It is white because of insulating wrappings around axons known as the "myelin sheath".

The idea that the brain is not a homogenous tissue is obvious to anyone.


How do nerve cells in the periphery protect themselves?

By having lots and lots of collagen fibres wrapping around them.


What is a myelin sheath?

The condensed cell membranes of the myelin sheath are mostly lipid, and give the white matter its white fatty appearance.

Myelination in the CNS is performed by oligodendrocytes (make many sheaths). In the periphery it is performed by Schwann cells (make only one sheath).


What do you see when creating a vascular cast of the capillary networks in great and white matter of the cerebral cortex?

The cerebral cortex, in particular the grey matter, is very richly vascularised.
The brain is one of the most vascularised structures, and within the brain it is the grey matter that is most vascular.
If the white matter is the axons and their wrappings, and the grey matter is the neurons.
No neuron seems to be more than 10 or 20 microns away from a capillary, keeping them close to glucose and oxygen and able to quickly get rid of carbon dioxide.


What are the neuronal energy requirements?

- energy demand high (15-20% of cardiac output)
- Obligate aerobic metabolism (O2 critical)
- totally dependent on glucose supply (via blood)
- Loss of O2 for a few minutes, glucose for 10-15 min is fatal to neurons (and neurons are vital)


What produces the cellular energy?

Mitochondria produce ATP aerobically.


How do we generate ATP in the brain?

- Only through aerobic metabolism.
- i.e. kreb's cycle etc


What is the fuel for the brain?

ATP generated via glucose only.


How is blood delivered to the brain?

- Most arterial blood goes from the outside in.
- large arterial vessels
- major vessels form three major territories
> anterior cerebral artery
> middle cerebral artery
> posterior cerebral artery
- mostly branch off internal carotid artery
- basilar arteries form the circle of Willis


What does the circle of Willis do?

Allows pressure to equalise on each side of the brain
- however a significant portion of the population don't have a complete circle so it can't be that important, at least in normal function (maybe if things go wrong)


Why is it important to know the different regions of the brain as defined by their blood supply?

The blood supply of the brain is to relatively specific regions - there is little overlap between them
If something goes wrong with the blood supply, the impact on the brain is defined by which aspect of the blood supply


What are CVAs?

- Cerebrovascular accidents
- CVAs or strokes are disruptions of the brains' blood supply
- loss of adequate blood flow causes loss of neuronal function and neuronal death
- CVAs are the most common cause of neurological disorder


What are the causes of CVAs?

Two causes:
- Occlusive: due to narrowing or closure of the vessels (atherosclerosis, thrombosis)
- Haemorrhagic: due to rupture of vessels (aneurysm, elevated BP, trauma, infection)

- this results in tissue ischaemia (reduced blood supply) and hypoxia/anoxia (decrease/loss of oxygen supply)


Are the results of a stroke consistent or random? Why?

- the vascular pattern is consistent between individuals as is the functional organisation of the brain, therefore strokes in a particular location produce characteristic loss of function


How can location determine whether a stroke is fatal?

- large stroke in the cerebrum may not be fatal even while a small stroke in the pons most likely would be
- this is because something like the pons is critical control area whose functions, if lost, mean the inability to sustain life


What are some causes of raised intra-cranial pressure?

- extravasation of blood (various types defined by location of bleeding in relation to meninges and brain parenchyma)

Vasogenic Odema
- increase in vessel permeability, increased ECF volume (head injury, meningitis)

Cytotoxic Odema
- swelling of cells, reduced ECF volumes (asphyxia or hypoxia)

- over-secretion of CSF or impaired absorption of CSF or obstruction in the circulation of CSF - esp. at the aqueduct)

CBF often reduces as ICP increase: cerebral perfusion pressure = arterial BP - ICP

> this means that increased ICP leads to an increase in blood pressure to try and balance the perfusion against the increased ICP.


What is the blood-brain barrier?

- capillaries in brain are not leaky
- a property of the CNS endothelial cells conferred by astrocytes
- tight junctions seal gaps to prevent proteins/other large molecules crossing
- only small things cross, big things remain
- e.g. glucose
- Paul Ehrlich experiment shows this through dye


What were Goldmann's Dye experiments?

- tryphan blue intrathecal injection showed only CNS stained
- tryphan blue intravenous injection showed CNS largely unstained


What are astroglia?

- aka astrocytes
- numerous functions including recycling of neurotransmitters and maintaining the ionic composition of the extracellular fluid


What does get through the blood-brain barrier?

- very small things
- also determined by a molecules lipid solubility so the fattier you are the easier to cross
- some things have protein transport processes


What is the microglial cell?

- ramified (resting) and ameboid (active)
- small macrophage-like cells that invade the developing brain (develop in the yolk sac) and reside as immune surveillance cells