Cellular Responses to CNS Injury

1. List the Cells of the CNS

2. Derived from? Sub types? Fxn?

CELLS OF THE CNS

1. Neurons: 

2. Glia: 

   • derived from neuroectoderm

   • Types:

     • Astrocytes: 

       • supportive function for neurons, 

       • repair cells,

       • Part of BBB

     • Oligodendrocytes

       • myelin production

     • Ependymal cells

       • line ventricles

3. Microglia

   • derived from the yolk sac

   • Fx: macrophage-like cells

4. Cells of the meninges and blood vessels

Draw out a schematic of the Neuron

Describe ASTROCYTES

• Histo

• Maintaining BBB mech?

• Supportive function?

• Response to Injury?

• Different types

• Histo:

  • H&E stain: only nuclei are seen

  • multiple branching cytoplasmic processes

  • Can be seen w/ metallic impregnation technique (e.g. Golgi method)

  • (+) for glial fibrillary acidic protein (GFAP)

• Maintaining BBB Mech:

  • By wrapping cytoplasmic processes around capillary walls

• Supportive Function:

  • structural & supply nutrients

• Response to injury:

  • reactive gliosis

    • *** brain’s version of scar tissue**

• Different types:

  • Gemistocytes: Reactive astrocytes

  • Astrocytomas: Tumors arising from astrocytes

Describe OLIGODENDROCYTES

• Fxn

• Histo

• Alignment

• Unlike Schwann Cells?

• What are tumors called?

OLIGODENDROCYTES

• Fxn:

  • Produce + maintain CNS myelin

    •  (counterparts of Schwann cells in the PNS)

• Histo:

  • few (oligo) dendrites

    • best visualized with a silver stain

  • Contain myelin basic protein (MBP)

• Alignment:

  • In white matter, aligned along axons

• Unlike Schwann cells

  • limited regenerative capacity

  • do not effectively remyelinate axons

• oligodendrogliomas

  • Tumors arising from oligodendrocytes

Describe EPENDYMAL CELLS

• What are they?

• Histo?

• Injury response?

• What type of cells are Choroid plexus epithelium

• What are tumors called?

EPENDYMAL CELLS

• What are they?

  • Single layer of columnar cells

  • Lines:

    • Ventricles

    • aqueduct of Sylvius 

    •  central canal of spinal cord

• Histo

  • Has cilia

  • Rest on subependymal glia

• Injury response:

  • Can’t Regen 

  • Causes subependymal astrocytic proliferation -> can obstruct aqueduct -> hydrocephalus

    • “ependymal granulations”

• Choroid plexus epithelium

  • form of ependyma specialized in production of CSF

• Ependymomas

  • Tumors arising from ependymal cells

Describe MICROGLIA

• Derived from?

• Fxn?

• Histo?

• Response to injury?

• Tumor?

MICROGLIA

• Derived 

  • yolk sac

• Fxn:

  • Mobile phagocytic cells

    • Similar cell markers w/ monocytes/macrophages

      • (e.g. CR3 & CD68)

  • brain development

• Histo:

  • only nuclei are seen on H&E stain

  • fine cytoplasmic processes w/ Silver Stains

• Response to Injury:

  • Reactive -> nuclei elongated (rod cells)

    • -> Microglial nodules

    • -> Neuronophagia

• Lymphomas

  • Tumors arising from microglia

Describe these Neuronal Responses to Injury:

• Axonal Reaction (Central Chromatolysis): 

  • Causes/Effect

• Acute Neuronal Injury

  • AKA?

  • Causes/Effect

• Neurodegeneration

  • Causes/Effect

• Neuronal Inclusions: 

  • Causes/Effect

Axonal Reaction (Central Chromatolysis): 

• Causes

  • axonal injury

• Effect:

  • reaction of perikaryon

  • Peripheral dispersion of Nissl substance 

  • peripheral displacement of nucleus

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Acute Neuronal Injury (Red Neurons): 

• Causes:

  • acute injury -> cell death

• Effect:

  • shrinkage of cell body, 

  • intense eosinophilia of cytoplasm, 

  • pyknosis of nucleus 

  • loss of Nissl substance

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Neurodegeneration: 

• Causes: 

  • subacute to chronic progressive neuronal injury

  • ALS & AD

• Effect:

  • gradual death & loss of neurons, 

  • reactive gliosis, 

  • Abnormal protein aggregates

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Neuronal Inclusions: 

• Causes/Effects (aggregates)

  • aging 

    • (lipofuscin),

  • viral infections

    • Cowdry bodies – herpes, 

    • Negri bodies - rabies

  • neurodegenerative diseases 

    • neurofibrillary tangles – Alzheimer disease, 

    • Lewy bodies – Parkinson disease

What can Accumulated misfolded proteins lead to?

Accumulated misfolded proteins can:

• Interfere with cellular metabolism

• initiation of the UPR

Describe the UPR process