Pathology of CNS

Question 1

Neurons in the CNS respond to…

Answer 1

1. Ischemia 2. Infections In different ways that are distinct to other tissues

Question 2

What may cells connected to a small injury cause?

Answer 2

It may result in a significant loss of function to the whole .

Question 3

What is the order susceptible to injury?

Answer 3

1. Neurons 2. Oligodendrocytes 3. Astrocytes

Question 4

What is the function of Astrocytes in the CNS?

Answer 4

1. Maintaining micro-environment 2. Important in maintaining the homeostasis of neuro-transmitters and ionic channels in the CNS 3. They are like the ‘garbage trucks’ where they pick up metabolites which are released in the CNS - such as GABA and maintaining the environment

Question 5

What is the function of Microglia cells in the CNS?

Answer 5

They are the Macrophages of the CNS - involved in tissue destruction and removing infectious elements within the CNS

Question 6

What is the function of oligodendrocytescells in the CNS?

Answer 6

Involved in myelination around the nuclei

Question 7

Which parts of the CNS are more prone to infarct or more risk from ischemia?

Answer 7

The areas that tend to occur between the main arteries: Between the Anterior Cerebral Artery (ACA) and the Mid-Cerebral Artery (MCA) or the Mid-Cerebral Artery (MCA) and the Post-Cerebral Artery (PCA). These areas are also know as the ‘watershed’ areas Similarly the Basal Ganglia and the Thalamus, the deeper structures of the brain are also at risk of ischemia & strokes because there is not any collateral supply in the deeper structures of the brain. Remember, around the brain there are meninges and so even the peripheral parts of the cortex maybe able to pick up some blood supply if there is ischemia. But the areas between the main cerebral arteries, deeper basal ganglion and thalamic regions are more at risk to ischemia.

Question 8

What is the histological feature on ischemia when a neuron is under stress?

Answer 8

The neurons will stain red indicating they are under stress with Hand E staining

Question 9

What is the reactions of Oligodendrocytes to injury?

Answer 9

Oligodendrocytes are circular nuclei of myelination of neurons within the CNS. They are not susceptible to ischemia as neurons have small round nuclei and in an Oligodendoglioma (tumour) there is an increase in cell number - hyperplasia. If you had a multiple sclerosis (MS) there would be a loss of oligodendrocytes which is a demyelination disease.

Question 10

What happens to the Astrocytes in Hyperplasia?

Answer 10

There is an increase of Gliosis, of the astrocytes with GFAD.

Question 11

What is the reactions of Microglia to injury?

Answer 11

Microglia, are the macrophages within the CNS and have these rod like nuclei. They respond to injury like any other macrophage and move to the site of damage where they try to initiate wound healing and repair. They will also phagocytise any necrotic tissue of the neurons or oligodendrocytes.

Question 12

Cerebrovascular Diseases:

Answer 12

• Hypoxia, ischemia and infarct - resulting for impairment of blood supply and oxygenation of tissue. Can be due to; Heavy smoker, old age, poor circulation that’s reducing O2 in your blood or a stoke etc. • Haemorrhage - resulting form a rupture of CNS vessels Can be an aneurysm in the brain resulting a rupture in a blood vessel.

Question 13

What determines the type of injury?

Answer 13

The type of injury depends on: 1. Presence of collateral blood supply - The location whether it has a good collateral blood supply whether it in that watershed region between the major cerebral arteries or steeper within the bran around the basal ganglia or whether its more peripheral around the cortex were there is some collateral supply form the meninges. 2. Duration of ischemia 3. Magnitude and time - Course of the reduction in flow (Acute Vs. Chronic) - How long, how sever restriction of O2 to the brain will determine how much damage is done

Question 14

What is a Global Cerebral Ischemia?

Answer 14

When there a Global Cerebral Ischemia the blood supply to the brain has essentially be chopped off though either a heart attack where the heart stops working and no blood is being pumped and the patient may end up being brain dead! It could also be caused by a trauma shock e.g. legs cut off and lost a massive fall in Blood pressure & volume and decrease the capacity to get O2 to the brain - risk of Global Ischemia.

Question 15

What is Focal Cerebral Ischemia?

Answer 15

• Embolus - traveling in blood • Thrombosis of artery - thinning of the artery • Vasculitits - inflammation

Question 16

Step Process in an Infarct: Long

Answer 16

During an infarct, you will see a pale region where the blood supply has been reduced/removed. One of the first signs within the tissue will be the nuclei staining red. A red nuclei = indicates the neurons are dying and undergoing necrosis/under a lot of stress. Releasing gluconate, GABA, calcium Loose their ability to maintain/regulate their internal homeostasis The will then become potentially toxic to the surround tissue Just as in any acute event, the first cells in the horizon are neutrophils that marginate/emigrate from the blood vessels in the surrounding areas and perfuse the area because the tissue is damaged. Neutrophils initially occur in the first day or 2, just as in acute inflammation Neutrophils will then recruit macrophages, the Microglia which will come into the area and initiate wound healing ad low down collagen fibres. Then finally the Astrocytes which are comparable to the fibroblasts within the peripheral/outside the CNS. The Astrocytes lay down the granulation tissue and collagen and try to re-organise the damaged area until the repairing and scaring of the wound within the brain. Naturally if the brain is scarred, the brain isn’t going to function too well - so lost of function with infarct.

Question 17

There are 2 types of infarcts:

Answer 17

Red Infarct = Haemorrhagic Infarct White Infarct = Non-Haemorrhagic Infarct

Question 18

What is a thrombosis?

Answer 18

is the thinning of the arteries causing a block (arterial block) Treatments can be given, Thrombocytopenia drugs given to break down the thrombosis and have restored function to the area.

Question 19

Define Penumbra:

Answer 19

The area surrounding the infarct where the tissue is at risk of damage/necrosis

Question 20

What is the function of Retinal Microglia?

Answer 20

• Microglia cells of the retina react to injury, and in young they are localised above the Outer Plexiform Layer. • These are important to the CNS as they as macrophages but also constantly on the look out for changes within the environment, like the surveyors of the CNS and within the retina where they check for pathology/diseases or changes in cell physiology. Neurons grow and extend making contact with the surrounding and making it ‘safe’.

Question 21

Compare the Microglia in the Retina in a Young person to an Old person:

Answer 21

If there are changes in the retina in relation to how microglia behave, that will then impact on how your retina is protected by these retinal microglial cells. So when your young, the microglia are essentially found in the outer plexiform layer and above.

Question 22

What changes occur in glaucoma to the Ganglion Cell Layer?

Answer 22

When the optic nerve is crushed induced by glaucoma, there is a destruction of axons thus there is a loss of ganglion cells.

Question 23

What causes glaucoma? (Pathogenesis)

Answer 23

• Age • Hypoxia • Trauma • Genetics - Runs in the family, more at risk • Diabetes Increase chances • Afro-Caribbean

Question 24

What happens to the RGC in high IOP?

Answer 24

With increasing IOP part of the pathogenesis of glaucoma is we induce apoptosis in our retinal ganglion cells (RGC) We still loose ganglion cells with age, retinal sensitivity goes and also loose neurons with the CNS Increasing IOP: TGF-Beta and Collagen type 1 increase with increasing IOP

Question 25

What is TGF-Beta secreted by?

Answer 25

The Macrophages so immune reaction against the optic nerve head when damaged. That’s why it correlates with the elevation of IOP.

Question 26

List way in which infections can arise within the body:

Answer 26

• Haematogenous Spread - Artery/Veins • Traumatic - Infections secondary to trauma or congenital malformation of Meninges - Brain injury form sinus or orbital cellulitis can cause infection to the brain. • Local - Sinus, teeth, Osteomyelitis • Peripheral Nervous System or the CNS (Zoster rabies feed back into the CNS)

Question 27

Define Acute Meningitis:

Answer 27

It is a life threating infection of the Meninges caused by bacterial or viral infection or even by TB

Question 28

There are 2 forms of Herpes:

Answer 28

1. HSV1 - Not sexually transmitted type, give rise to cold sores. Can get into the CNS and affect the temporal and frontal lobes. Frontal Loves - being your emotional well-beings, higher congentive thoughts are going to be impaired, so may notice a big change in mood or behaviour with HSV1. HSV2 - Congenital Herpies - Half new born-children born to a mother with HSV, with Herpies will contract Herpies on the way out and its going to then develop into a Viral Meningitis/Encephalitis

Question 29

what is Motor Neuron Disease

Answer 29

• is another CNS disease which genetic origin that affects the motor neurons of the ventral part of the spinal cord and the motor cortex. The dorsal and sensory roots are fine but the ventral horn/root of the motor neurons are atrophied.

Question 30

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Answer 30

This Infarct (bottom left corner) could be due to a thrombosis form the heart, circulating into the internal carotid artery and getting lodged somewhere in the brain and causing an infarct where it tend to be red and a leakage of blood from the area.

Question 31

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Answer 31

Here is a bone marrow embolism, possible caused by a fracture so if you fracture your bone, you release bone marrow which move up and cause infarcts within the CNS

Question 32

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Answer 32

In The younger retina - A&B You can see the microglia cells are limited to the outer plexiform layer and in the inner plexiform layer and ganglion cell layer. Only about one microglial cell is found in the RPE. But when your aged - the microglia migrate, you tend to find more microglia in the RPE and they break though from the outer plexiform layer and you may find microglia In the subarachnoid space where you wouldn’t get any microglia in a young persons.

Question 33

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Answer 33

Microglia secrete neuroproective substances as well as being macrophages - so important for the maintenance of the health of the neural retina. Not only do the microglia migrate down towards the RPE and down maintain on the outer plexiform layer but they also lose their ramification - that is the number of branches, they become less branchy and so they are less able to touch/feel the surrounding neural tissues. The movements in a younger microglia are greater, bigger and more frequent than the older microglia Movements are reduced in the older microglia

Question 34

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Answer 34

Axons shrink/extend and survey the environment more process extension and retraction in young than old.Microglia don’t move as fast or retreat form injury as quickly as they do in young

Question 35

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Answer 35

Laser Burns - Put a hole in the retina and so there is tissue damage in both the young and old. The microglia are going to macrophage or phagotose the damage tissue in both the young and old. Microglia arrive the same time and about the same numbers too BUT microglia in the older retina takes longer to disperse.

Question 36

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Answer 36

Modern technology: Finds the limit of Bruch’s membrane and that denotes the disc margin and does a ration to the cup size and where Bruch’s membrane is = Far better way of assessing CD ratio

Question 37

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Answer 37

In this picture it is definitely an infection here as you can see the puss discharge associated with bacteria. If you were to so a Spinal Tap the CSP would be cloudy, full of neutrophils, decrease in the concentration of glucose because the bacteria is eating up all the glucose. In a viral Meningitis the Spinal Tap is clear, not so cloudy and glucose would be high. But in both cases patients will complain of headaches, blurry visions and mood swing

Question 38

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Answer 38

Viral infection of the brain - these are caused by ArboViruses such as mosquitos or insects… When people come back from holidays and return with fevers and seizures

Question 39

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Answer 39

There are 2 forms of Herpies: 1. HSV1 - Not sexually transmitted type, give rise to cold sores. Can get into the CNS and affect the temporal and frontal lobes. Frontal Loves - being your emotional well-beings, higher congentive thoughts are going to be impaired, so may notice a big change in mood or behaviour with HSV1. 2. HSV2 - Congenital Herpies - Half new born-children born to a mother with HSV, with Herpies will contract Herpies on the way out and its going to then develop into a Viral Meningitis/Encephalitis Image on the bottom right shows clusters in typical viral infections such as HIV of astrocytes and microglia and macrophages trying to remove the viral particles in these small vascular cuffs

Question 40

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Answer 40

People who abuse alcohol, end up staggering etc. because their cerebellum gets wiped out which is involved in fine control and regulating eye movements.