Lecture 9-10

• Basic anatomy of the brain:

  • Extensive blood supply.
  • Meninges: 3 membranes surrounding the brain.
  • cerebrospinal fluid: between the brain and the membranes that drains into the arachnoid villi, and is there to protect the brain.  
• What are the different brain cellular components?

  Neurons, glial cells
• what are the different types of glial cells and what do they do?

  There are several types of glial cells, including astrocytes, oligodendrocytes, and microglia. Astrocytes provide structural support and regulate the chemical environment of neurons. Oligodendrocytes produce myelin, which insulates and speeds up nerve impulses. Microglia are involved in immune defense in the central nervous system.
• There is extensive communication between neurons and glial cells
• what is meningitis?

  Inflammation of the membranes surrounding the brain and spinal cord.
• what are symptoms of meningitis?

  fever, headache, stiff neck, mental alterations, photophobia
• Bacteria reach the meninges through the blood-CFS barrier
• meningitis infection initially confined to the subarachnoid space, BUT in severe cases it spreads within the brain
• the types of bacteria that can cause meningitis infection varies with age
• which pathogens can lead to meningitis?

  Neisseria meningitis and E. coli
• Neisseria meningitis:  

  • Mostly just stays within the nasopharynx and doesn’t cause damage.
  • specific properties: have projections that can latch on to cells (have adhesins on capsule that bind to specific receptors)
• E. coli can also cause meningitis:

  • Passes through the endothelium of the cerebral vasculature without any disruption of the endothelial cell.
  • The endothelium forms a vacuole to transport the bacterium across the cell.
  • They have a capsule that prevents fusion with lysosomes.
• Two forms of neuronal injury caused by meningitis:

  • Necrotic cortical injury
  • Apoptotic hippocampal injury
• what is an abscess?

  an internal localized area of infection
• what is encephalitis?

  Inflammation of the brain.
• what can cause encephalitis?

  Herpes viruses, HIV
• what is viral meningitis?

  Inflammation of the meninges caused by a viral infection.
• what are the effects of HIV on the CNS?

  demyelination in cortex, cause a peripheral neuropathy, can result in dementia
• how can HIV enter the brain?

  by itself or can use T-cell or Monocyte/Macrophage
• what is a parasitic cerebral infection?

  Cerebral malaria
• Cerebral malaria mainly occurs in children.
• prion disease was first recognized by Mad cow disease
• how did mad cow disease occur?

  Problem occurred since they were feeding ground up sheep that were infected by the disease
• what is prion disease?

  Prion disease is a group of rare, progressive neurodegenerative disorders caused by abnormal proteins called prions.
• prion disease destroys whole sections of the brain and causes bovine spongiform encephalopathy
• Current problem in Canada:

  • Chronic wasting disease in deer, elk, moose
  • Killing Canadian wildlife
  • Potential risk to humans
• what are consequences of traumatic brain injury?

  • Primary damage: scalp laceration, skull fracture, intercranial hemorrhage – immediate.
  • Secondary damage: ischemia, hypoxia, cerebral swelling, infection – delayed. 
  • 4 basic things that are happening: neuronal death and tissue loss, BBB breakdown and edema, gliosis and cell infiltration, upregulation of inflammatory regulator.
  • Injury complicated by multi-trauma effects.
• what is herniation?

  increase intercranial pressure causing displacement
• common sites if herniation is the front and the back of the brain
• Glasgow coma scale allows us to quantify the level of brain damage.
• what are symptoms of Parkinson's disease?

  rhythmic tremor and cogwheel rigidity of joint
• what are Lewy bodies?

  Abnormal protein (aggregates alpha synuclein) found in the brain.
• what causes the symptoms Parkinson's disease?

  Due to changes in the basal ganglia, there is a loss of dopamine (loss of dopaminergic neurons in the substantia nigra)

  Microglia are activated so there is an inflammatory response.

  deposits of Lewy bodies
• what are current concepts of Parkinson's disease pathogenesis?

  Must lose a lot of neurons to start seeing symptoms: must have at least 20% of neurons to have normal function. So, there must be something going on sooner in life that destroys neurons. Some think that there is possibly impaired autophagy and inability to remove abnormal proteins. Others think the microbiome causes this.
• what is the microbiome hypothesis?

  Since it was realized that Lewy bodies can go in the brain via vague nerve and that they are made in the periphery, something might be wrong with the microbiome and they make more Lewy bodies
• what are Alzheimer symptoms?

  Dementia: cognitive, motor, language, sensory impairment
• what are the brain alterations that occur in Alzheimer's?

  • Intra-neuronal tangles: microtubular associated protein tau
  • Plaques: beta amyloid, tau filaments and gliosis
  • Mitochondrial dysfunction, cholinergic insufficiency, inflammation, autophagy dysfunction.
  • Angiopathy beta amyloid (deposition of amyloid around blood vessels)
• Time course of Alzheimer's:

  1. Preclinical AD – no symptoms
  2. Mild cognitive impairment due to AD – very mild symptoms that don’t interfere with everyday activities.
  3. Dementia due to AD (mild) – symptoms interfere with everyday activities.
  4. Dementia due to AD (moderate)
  5. Dementia due to AD (severe)
• Processing of amyloid precursor protein (APP):

  • APP normally turned over and can be cut up by secretases, and depending on where they cut you can get two things:
  • It is cut with the alpha and gamma, but if cut by beta and gamma can cause problem.
  • Creates AB peptide that can aggregate and form plaques.
• Life expectancy is continually increasing