Disorders of the CNS

Question 1

Principal barriers against microbes and metabolites (protective mechanism)

Answer 1

CSF

Question 2

CSF flows through:

Answer 2

The subarachnoid space

Question 3

Glial cells (3 types):

Answer 3

• Oligodendroglial (myelin)
• Astrocytes (caretaking functions, cope with stress by changing the properties)
• Microglial (Macrophage in the CNS)

Question 4

Depend on the ages, some bacteria infection in meningitis are more frequent:

1. Neonatal
2. Infant
3. Adult

Answer 4

Neonatal: E coli
Infant: Hemophilus influenzae
Adult: Neisseria meningitidis and Streptococcus pneumonia.

Question 5

Meningitis infection is normally confined to the:

Answer 5

subarachnoid space.

Question 6

Neisseria Meningitis is the colonization of bacteria in the:

Answer 6

Nasopharynx

Question 7

Neisseria Meningitis pathways:

Answer 7

• Adhere to nonciliated epithelium
• Produce an proteases inactivate IgA (major protective antibody in the nasopharynx, GI and lung)
• Polysaccharide capsule (inhibit phagocytosis), Mimic neural cell adhesion molecule, Vary the surface expression of antigens (versatile microbe)
• Immune system is triggered by the endotoxin.
• Neutrophil proteolytic enzymes damage endothelium
• Shock, intravascular thrombosis, system failure.

Question 8

When the CNS is damage: (cycles of events)

Answer 8

• BBB disrupture, damage the epithelial cell
• Swelling of individual cells –>hydrocephalus –>cerebral oedema
• Brain damage (compression–> herniation)

Question 9

Special feature of E coli:

Answer 9

K1 capsule, prevents fusion with lysosome (protect itself)

Question 10

2 forms of neuronal injury in meningitis:

Answer 10

1. Necrotic cortical injury

2. Apoptotic hippocampal injury

Question 11

HIV CNS infections:

Answer 11

demyelination in cortex, peripheral neurophaty, dementia…

Question 12

HIV neurotoxicity:

Answer 12

• HIV infects microglia (have the receptors on the surface for the virus to get in)
• HIV proteins, cytokines and various neurotoxins released by the infected microglia
• Change in the neurons and astrocytes.

Question 13

Prion diseases is:

Answer 13

Infectious diseases cause by a abnormal form of a cellular protein.

Question 14

The abnormality in the protein causing scrapie:

Answer 14

Beta sheet form –> Beta helix

Question 15

Prion diseases pathways:

Answer 15

Inoculation
Interaction (PrPc --->PrPsc)
Conversion/propagation 
Accumulation (aggregation)
Neuronal toxicity (change in the astrocytes)

Question 16

Examples of prion diseases:

Answer 16

Scrapie, Mad Cow or BSE (bovine spongiform encephalopathy)
Kuru
Creutzfeldt-Jakob disease
Spongiform encephalopathies

Question 17

Cerebral Trauma injury steps:

Answer 17

• Primary injury
• Progressive damage (delayed damage/ secondary damage) –> (mediators calcium, free radicals, inflammation, receptor dysfunction)
• Additional injury (ischemia, Seizures, infection, oedema, fever)
• All this event will determine the Functional Outcome.

Question 18

Parkinson’s disease symptoms:

Answer 18

(cause problem with the motor function)

• Rhythmic tremor
• Cogwheel rigidity

Question 19

Parkinson’s disease is due to:

Answer 19

• Change in the substantia nigra in the brain. (Decrease of the dopaminergic neurons)
• Spread of the A-Synuclein in the brain linked to dopamine turnover.
• Lewy body (cluster of A-Synuclein)

Question 20

BEfore having the symptoms of Parkinson’s disease you need to loose (%) of the dopaminergic neurons?

Answer 20

80%

Question 21

Environmental insult getting ride of a number of neurons in early ages. Possible causes?

Answer 21

Exposure to toxin/ infection

Question 22

Alzheimer’s Disease generals principles:

Answer 22

• NOT GENETIC (brain plasticity, always changing to adapting)
• NOT a natural cause of dead.
• Major factor are environmental.

Question 23

Alzheimer’s Disease is due to:

Answer 23

• Intraneuronal: tangles of proteins tau–>neurofibillary tangles (microtubular associated proteins tau.)
• Extraneurons: Plaque of beta-amyloid, tau filaments and gliosis
• Causing damage from the inside and outside of the neurons. (shrink, retract their processes and die)

Question 24

Beta-Amyloid formation pathogenesis:

Answer 24

• Normally, you get ride of the amyloid precursor protein (APP) with alpha, beta and gamma secretases.
• Beta-amyloid is get ride of when APP is cleaved by the alpha and gamma.
• Beta-amyloid is created when APP is sequentially cleaved by the Beta-amyloid converting enzyme (BACE) and gamma secretase,
• Beta-amyloid is a larger section that aggregate, form plaques, lead to neuronal death, elicit local inflammatory response –> cell injury/alter communication through axons and dendrites.

Question 25

Prevention of Alzheimer’s disease:

Answer 25

1/3 of the cases could be prevented or delayed due to lifestyle: 9 factors (midlife hearing loss, failing to complete secondary education and to seek early tx for depression, smoking, HBP, obesity, social isolation, physical inactivity and type 2 diabetes)