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Mechanisms of human disease > Central nervous system diseases > Flashcards

Flashcards in Central nervous system diseases Deck (34):
1

What are the protective features of the CNS?

The meninges (dura mater, arachnoid mater and pia mater), the skull and vertebral column, cerebral spinal fluid, the blood brain barrier and the glia cells.

2

How does the cerebrospinal fluid protect the brain?

It acts as a shock absorber, cushioning the brain so that it doesn't smash into the skull.

3

How does the blood brain barrier protect the brain?

The blood brain barrier acts as a quarantine for the brain, by removing toxic substances, other bodily compounds that shouldn't be in the brain and keeps the brain's CSF stable in the event of bodily fluctuations.

4

What is the difference between the grey and white matter of the brain?

The grey matter contains the unmeylinated structures, like the cell bodies, dendrites, blood vessels and glial cells. The white matter is myelinated and it contains the axons.

5

What are the glial cells and how do they protect the brain?

Glial cells refer to a collection of cells found in the brain that are not neurons or blood vessels. The glial cells include the oligodendrocytes (myelin factories), astrocytes (homeostasis), microglia (immune surveillance), ependymal cells (lining of ventricles and canal) and the adult progenitor cells.

6

How exactly do the glial cells, oligodendrocytes work?

They work by supporting the neurons, and they are the myelin factories for the axons. One oligodendrocyte is connected to and supplies myelin to 4-40 other neurons.

7

What is myelin's role with the neurons?

Myelin increases the speed of impulse propagation down the axon and prevents current leakage between the neuronal spaces.

8

How exactly do the glial astrocytes work?

There are two types of astrocytes, the protoplasmic ones that spread their processes radially and are in the grey matter. Then there are the fibrous astrocytes that are found in rows between the axons and they send processes to the myelinated axons. Astrocytes work by maintaining homeostasis. The astrocytes are highly organised in the brain to ensure that none of them overlap.

9

How exactly do the glial microglia work?

Microglia are actually macrophages that moved to the brain in fetal development before the blood brain barrier was formed. Their role is to act as the first line of defense for the brain by removing debris and acting against any viruses, bacteria and parasitic CNS pathogens. Sometimes, they work with astrocytes to maintain homestasis.

10

What is immune privilege with regards to the microglia?

Immune privilige refers to the iscolation and exclusivity that the brain has from the rest of the body via the blood brain barrier. This means that the brain is protected against most of the immunological threats to the rest of the body. However, because of this lack of exposure and high protection, the brain has a very low capacity to protect itself from pathogens that do cross the blood brain barrier. This puts a lot of pressure onto microglial macrophages to quickly detect and destroy pathogens because the brain tissue is vulnerable.

11

Are leukocytes an exception to the blood brain barrier because they are protective?

Under normal healthy conditions, the cells are not able to pass through the blood brain barrier. It is only in the presence of brain inflammation or disease that they get special permission to enter into the brain and assist in healing. This is facilitated by the memory t-cells that are present in the CSF.

12

Where do these glial cells originate from embryologically?

The microglia arise from the mesoderm. The neurons, astrocytes, oligodendrocytes and the ependyma glial cells all arise from the ectoderm though.

13

What are adult neural progenitor cells and where are they found?

These are basically brain stem cells that are found in the brain. They look like glial cells and have the potential to differentiate into astrocytes, oligodendrocytes or neurons.

14

Explain what acute neuronal injury is.

It is also known as 'red neuron'. Acute neuronal injury occurs during a sudden injuring event like ischaemia or hypoxia that cut off the neurons oxygen supply. This results in the shrinkage of cell body, loss of the Nissl substance (specialised version of the ER for neurons), the dissapearance of the nucleus and eosinophil infiltration of the cytoplasm. This leads to the death of the neuron and it is phagocytosed as debris by the microglia cells.

15

Explain what subacute and chronic neuronal injury is.

It is basically when the neuron has been injured by non ischemic means, and this traumatic event causes damage not to the neuron directly, but to the glial cells that support it. Damaged glial cells undergo gliosis, in which the glial cells start madly proliferating and producing other cells and this causes so much damage to the neurons that they undergo apoptosis and are degenerated.

16

Explain what transynaptic degeneration is.

Transynaptic degeneration describes a tsunami of neuronal death that starts from one malfunctioning neuron. If one neuron for whatever reason becomes overstimulated by a neurotransmitter, then it will enter into neuronal dysfunction, killing or damaging it. Then, this malfunctioning neuron does not spread the neurotransmitter to the next neurons, which become deprived and also enter into a state of metabolic deficit and they die too. This cycle continues, killing many neurons because they are connected to each other.

17

Explain what axonal reaction is.

Axonal reaction refers to when damage to the axon, causes damage to the cell body, which eventually kills the entire neuron. It starts when the axon is damaged which injures the cell body. The cell body swells up, dislocates the nucleolus and causes dissolution of the Nissl substance. This combination kills the cell body and thus, the entire neuron.

18

In which ways do astrocytes respond to injury?

They respond by undergoing gliosis, which means astrocyte hypertrophy and then hyperplasia causing their death. These masses of dead astrocytes form pathological structures in the brain called 'rosenthal fibres'. These fibres are just accumulations of dead astrocytes that have been infiltrated by eosinophils

19

Can oligodendrocytes respond to injury?

No, they don't typically respond to injury. They can be injured but have the ability to be replaced from their progenitor pool. Oligodendrocytes can also replace lost myelin, even if it is a thinner layer.

20

How do microglia respond to injury in the brain?

Microglia actually become activated when they detect neuronal injury. The more severe the injury, the more activation. The microglia proliferate and express CD4+ T cells, MHC 1 and 2 antigens and cytokines when they detect injured neurons. However, when they detect dead neurons, they are activated and become phagocytotic, and they ingest the dead neurons to clear space. They also secrete heaps of degradation cytokines and repair cytokines.

21

Describe neuronal trauma as an injuring stimulus?

Neuronal trauma refers to the physical interference or delivery of a sudden force that causes damage to the brain. Neuronal trauma effects are often silent and the extent of damage will depend on the location of the lesion/injury.

22

What is the common name for cerebrovascular disease and how does it work?

Cerebrovascular disease is more commonly known as a stroke. It involves a sudden ischaemic or hypoxic event that deprives a certain part of the brain from blood and oxygen. The longer the deprivation, the more damage is inflicted on the neurons. Hemorrhaging or internal bleeding of the affected brain area can occur causing more damage.

23

What is focal cerebral ischaemia?

It just refers to a type of cerebrovascular disease in which a specific region of the brain in iscolation is ischaemic, and so the damage is restricted to that area only. It is typically caused by the occlusion of that particular cerebral artery.

24

What is intracranial hemorrhage?

This is another type of cerebrovascular disease. Basically, it is a spontaneous rupture of a cerebral artery, that results in internal bleeding of the brain. It can be caused by long-term hypertension, which is known to weaken blood vessel walls. Or it could be caused by amyloid angiopathy, where amyloid deposits on cerebral artery walls causes them to weaken and rupture.

25

Name three bacterial infections of the brain.

Meningitis, which is acute inflammation of the CSF and the meninges. There is encephalitis, which is acute inflammation of the brain's parenchymal cells (e.g neurons) and even meningoencephalitis, which is simply both.

26

What effect do demyelinating diseases have on the brain?

They cause damage to the myelin sheath, but the axons are usually intact. This results in poor or inhibited axon propagation from the lack of myelin coating.

27

What are the diseases of the grey matter?

Alzheimers and Parkinsons diseases are both diseases of the grey matter. These diseases are degenerative and involve the targeting and death of specific neuronal areas by protein aggregates.

28

Name two genetic metabolic diseases of the brain.

Neuronal storage disease- this causes an enzyme deficiency in the lysosomes that results in the build-up and not the degradation of debris by the lysosomes. The accumulation of substrate within the lysosomes results in the death of neurons.
Leukodystrophies- are myelin abnormalities that cause problems with the white matter.

29

What is MPTP induced parkinsons disease?

This disease was discovered when a group of teens intravenously took synthetic heroin or MPTP, and all presented with parkinsons like symptoms the next day. MTPT was found to damage the neurons of the substantia nigra in the brain, resulting in the parkinson's disease like symptoms.

30

What is primary traumatic injury to the brain and what does it entail?

Primary traumatic injury involves injury of the brain caused by an external, physical force. The brain's protection against primary traumatic injury is the skull and the CSF that act as shock-absorbers and a helmet. During primary traumatic injury, the brain is susceptible to tearing, shearing and stretching of the individual gyri (wrinkled folds of the brain). This results in acute neuronal injury, axonal damage and even hemorrhage.

31

What is secondary traumatic injury to the brain and what does it entail?

Secondary traumatic injury involves the exposure of the brain to excessive amounts of cytokines, ROS's and inflammatory mediators that can cause disruption to the blood brain barrier functioning, resulting in oedema. The oedema increases the intracranial pressure inside the skull, which can cause hypoxia and ischemia, hemorrhage and herniation- which ultimately cause neuronal death.

32

What changes occur in the blood brain barrier during inflammation?

The blood brain barrier needs to become permeable to important immune cells in the initiation of inflammation. During brain injury or inflammation, the astrocytes become activated and they cause reduced integrity of the endothelial cell tight junctions. Transendothelial channels are formed within the blood brain barrier and this is how the leukocytes are able to enter the brain.

33

What is the effect of intracranial pressure herniation on the brain?

The intracranial pressure herniation can cause displacement of the brain within the skull. The herniation of one region of the brain squashes and compresses other regions of the brain, which causes more damage.

34

What are the two brain stem cells that are capable of brain repair and regeneration?

There are the adult neural stem cells (NSC's) and the NG2 glia. They NSC's are capable of self-renewal and differentiation into neurons. The NG2 glial steme cells are found throughout the brain parenchymal cells and they are able to differentiate into oligodendrocytes.