Normal Brain Histology & Basic Neuropathologic Reactions

Question 1

What is unique about the CNS? (3)

Answer 1

Selective vulnerability of neuronal systems

Mature neurons are post-mitotic cells

Unique anatomic/physiologic characteristics

Question 2

What are some unique anatomic/physiolgic characteristics of the CNS? (6)

Answer 2

• Bony enclosure
• Metabolic substrate requirements (glucose, O2)
• No lymphatic system
• Presence of CSF
• Limited immune surveillance
  
  • Physical barrier – BBB
• Distinctive response to injury & healing (astrocytic reaction)

Question 3

Normal neurons are integrating & transmitting cells of the CNS, using _______ & _______ means.

Morphology varies by ______.

Answer 3

chemical & electrical

location

Question 4

What is unique about the nucleus of normal neurons?

Answer 4

• Most have large nucleus w/ prominent nucleolus
• Well-defined cytoplasm containing Nissl substance
  
  • Nissl substance = rER
• Branching processes (dendrites) & longer cell process (axon)
  
  • Axons have terminal synapses for chemical transmission to another neuron

Question 5

Where are these neurons located?

• Pyramidal & granular neurons
• Betz cells
• Granular neurons
• Purkinje cells
• Anterior horn cells
• Globoid shaped cells
• Melanin containing cells

Answer 5

• Pyramidal & granular neurons
  
  • **Cerebral cortex **
• Betz cells
  
  • **Primary motor cortex **
• Granular neurons
  
  • Hippocampus & cerebellum
• Purkinje cells
  
  • Cerebellum
• Anterior horn cells
  
  • **Spinal cord **
• Globoid shaped cells
  
  • **Deep gray nuclei **
  • Basal ganglia, thalamus, brainstem
• Melanin containing cells
  
  • Brainstem
  • Substantia nigra, locus ceruleus

Question 6

What type of cell is this?

Answer 6

Anterior horn cells (motor neuron)

Question 7

What type of cell is this?

Answer 7

Cerebral cortex neurons

Pyramidal shape

Question 8

What type of cell is this?

Answer 8

Neuromelanin-containing neurons in brainstem

Substantia nigra, locus ceruleus, motor nucleus of vagus

Question 9

What type of cell is this?

Answer 9

Granular neurons of the dentate fascia of the hippocampal formation

Question 10

What type of cell is this?

Answer 10

Purkinje cells & granular cells of the cerebellar cortex

Question 11

_______ accumulates in neuronal cytoplasm w/ age.

Answer 11

Lipofuscin

Question 12

Cerebral neocortex (isocortex) contains ____ layers, numbered sequentially from ______ to _______.

Answer 12

6 layers

superficial to deep

Question 13

What is this?

Answer 13

• Cerebellum
• ML = molecular layer
• PCL = Purkinje cell layer
• GCL = granular cell layer
• WM = white matter

Question 14

What are the reactions of neurons to injury? (3)

Answer 14

• Eosinophilic changes (ischemia/hypoxia)
• Central chromatolysis (axonal damage)
• Intraneuronal inclusion formation

Question 15

Eosinophilic Degeneration

Definition

Morphologic criteria

Answer 15

• Indicated lethal ischemia, hypoxia or hypoglycemia
• 12-24 hrs to manifest (light microscope level)
• Morphologic criteria
  
  • Shrinkage of neuronal cell body
  • Loss of Nissl w/ cytoplasmic eosinophilia
  • Loss of nucleolus w/ nuclear pyknosis

Question 16

What is this?

Answer 16

Scattered acutely hypoxic/ischemic neurons

(Eosinophilic Degeneration)

Question 17

Central Chromatolysis

Definition

Reversible or Irreversible?

Histology

Answer 17

• Manifestation of switch from manufacture of synaptic to structural proteins in response to axonal damage
• Reversible, if axonal repair is successful
• Cellular swelling w/ margination of Nissl substance & nucleus
• Accumulation of filaments & organelles

Question 18

What are the 2 types of glial cells of the CNS?

Answer 18

• “Macroglia”
  
  • All derived from neuroectoderm
  • 90% of CNS cells
    
    • Astrocytes
    • Oligodendrocytes
    • Ependymal cells
• Microglia
  
  • Derived from bone marrow

Question 19

Astrocytes

Characteristics

Components

Answer 19

• Primary replicating cell w/i CNS
• Round to oval nucleus (10 μm) w/ radiating cytoplasmic processes
• Star-shaped cytoplasm, normally invisible on H&E staining (unless reacting to injury)
• Glial fibrillary acidic protein (GFAP) – major cytoplasmic structural protein
• Ab to GFAP help visualization of astrocytes

Question 20

Astrocytes

Function (4)

Answer 20

• Contribute to BBB
  
  • Cytoplasmic processes (end-feet) on blood vessel walls
  • Control flow of macromolecules btwn blood, CSF & brain
• Responsible for repair & scar formation
• Maintain extracellular environment
  
  • Metabolic buffers or detoxifiers & supply nutrients
• Structural support

Question 21

What are reactive astrocytes?

Answer 21

• Astrocytes activate in response to various pathologic conditions
• Provides evidence of disease process
• Astrocytes divide & become larger
  
  • Increase in GFAP filaments reflected in visible eosinophilic cytoplasm
  • GFAP Ab will help identify the reactive astrocytes
  • Cytoplasm may appear starlike (fibrillary) or large & round (“gemistocytic”)

Question 22

Oligodendroglia

Definition

Characteristics

Answer 22

• Responsible for myelination in CNS
• White matter >> gray matter
• Smaller nucleus & fewer processes than astrocytes
  
  • Round dense nucleus
  • Peri-nuclear halo (artifact)
• Do NOT synthesize GFAP
• Lethal injury –> demyelination

Question 23

What are 3 important diseases involving oligodendrocytes?

Answer 23

• Multiple Sclerosis
• Progressive Multifocal Leukoencephalopathy
• Oligodendrogliomas

Question 24

Ependymal cells (Ependyma)

Characteristics

Answer 24

• Cuboidal to columnar glial ciliated cells that line vestibular surfaces
• Lateral surfaces have cell junctions forming CSF-brain barrier

Question 25

**Choroid Plexus** Characteristics

Answer 25

* Tufts of epithelium projecting into ventricles * Secrete CSF * Papillary architecture * Cell junctions btwn cells ensure CSF-brain barrier

Question 26

**Microglia** Definition Histology

Answer 26

* Monocyte/macrophage-derived cells that reside in the CNS * Normally inconspicuous, sparse, rod-shaped nuclei w/o visible cytoplasm

Question 27

What happens to microglia w/ **CNS injury**?

Answer 27

**With CNS injury, may become activated** * Migrate to site of injury * Proliferate * May differentiate into tissue MΦ * Foamy clear cytoplasm

Question 28

What happens to microglia w/ **viral infections**? HIV?

Answer 28

* In **viral infections**, astrocytes & microglia form microglia nodules at sites of neuronal injury * **HIV infection** stimulates cellular fusion resulting in multinucleated giant cells in microglial nodules

Question 29

What is the **Virchow-Robin space**? What is a **Neuropil**?

Answer 29

* **Virchow-Robin Space** * Large arteries w/i the subarachnoid space supply the brain by penetrating into the parenchyma * Initially maintain a perivascular space * **Neuropil** * Network of dendrites & axons in the gray matter * In btwn the cell bodies

Question 30

What are **Meningothelial Cells**?

Answer 30

* Present throughout the arachnoid membranes covering the _brain_ & _spinal cord_