Disorders of the CNS Flashcards
Principal barriers against microbes and metabolites (protective mechanism)
CSF
CSF flows through:
The subarachnoid space
Glial cells (3 types):
- Oligodendroglial (myelin)
- Astrocytes (caretaking functions, cope with stress by changing the properties)
- Microglial (Macrophage in the CNS)
Depend on the ages, some bacteria infection in meningitis are more frequent:
- Neonatal
- Infant
- Adult
Neonatal: E coli
Infant: Hemophilus influenzae
Adult: Neisseria meningitidis and Streptococcus pneumonia.
Meningitis infection is normally confined to the:
subarachnoid space.
Neisseria Meningitis is the colonization of bacteria in the:
Nasopharynx
Neisseria Meningitis pathways:
- 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.
When the CNS is damage: (cycles of events)
- BBB disrupture, damage the epithelial cell
- Swelling of individual cells –>hydrocephalus –>cerebral oedema
- Brain damage (compression–> herniation)
Special feature of E coli:
K1 capsule, prevents fusion with lysosome (protect itself)
2 forms of neuronal injury in meningitis:
- Necrotic cortical injury
2. Apoptotic hippocampal injury
HIV CNS infections:
demyelination in cortex, peripheral neurophaty, dementia…
HIV neurotoxicity:
- 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.
Prion diseases is:
Infectious diseases cause by a abnormal form of a cellular protein.
The abnormality in the protein causing scrapie:
Beta sheet form –> Beta helix
Prion diseases pathways:
Inoculation Interaction (PrPc --->PrPsc) Conversion/propagation Accumulation (aggregation) Neuronal toxicity (change in the astrocytes)
Examples of prion diseases:
Scrapie, Mad Cow or BSE (bovine spongiform encephalopathy)
Kuru
Creutzfeldt-Jakob disease
Spongiform encephalopathies
Cerebral Trauma injury steps:
- 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.
Parkinson’s disease symptoms:
(cause problem with the motor function)
- Rhythmic tremor
- Cogwheel rigidity
Parkinson’s disease is due to:
- 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)
BEfore having the symptoms of Parkinson’s disease you need to loose (%) of the dopaminergic neurons?
80%
Environmental insult getting ride of a number of neurons in early ages. Possible causes?
Exposure to toxin/ infection
Alzheimer’s Disease generals principles:
- NOT GENETIC (brain plasticity, always changing to adapting)
- NOT a natural cause of dead.
- Major factor are environmental.
Alzheimer’s Disease is due to:
- 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)
Beta-Amyloid formation pathogenesis:
- 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.
Prevention of Alzheimer’s disease:
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)
