Understanding neuroanatomy, histology, and physiology are integral for medical students who are laying the foundation of neurology. For residents and fellows, reviewing such material serves as a refresher of topics not regularly confronted in clinical practice but are often seen on in-service and board examinations. In this section, we will cover CNS histology, anatomy as well as briefly mention some associated neurological syndromes.

Authors: James Eaton MD, Steven Tessier, Brian Hanrahan MD

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Central Nervous System Histology

Illustration and microscope slide with H&E stain showing glial cells and neurons
Illustration (left) and microscope slide with H&E stain (right) showing glial cells and neurons

Glial cells

  • May be classified as macroglia (which include astrocytes, oligodendrocytes, and ependymal cells) and microglia.
  • Provide support and protection for neurons.
  • Glial cells outnumber neurons 10 to 1 in the central nervous system.

Astrocytes

  • The largest glial cell.
  • Support function of neurons in multiple ways:
    • Regulates interstitial fluid.
    • Modulates signals that regulate blood flow in response to neuronal activity.
    • Provides structural support; astrocytes are essential components of the blood-brain barrier and of glial-limiting membranes (aka glial limitans) that line the pia matter and parenchymal vasculature.
    • Provides nutritional support via glycogen storage.
    • Protects against the death of neurons by activating antioxidant pathways.
    • Expresses the enzyme glutamate synthase which is important for the removal of excess glutamate and GABA from synapses. Glutamate synthase also plays a role in the detoxification of ammonia.
    • Produces numerous angiogenic factors including VEGF.
      • VEGF decreases the stability of the blood-brain barrier with inflammatory conditions and CNS tumors.
  • Immunohistochemical staining for glial fibrillary acidic protein (GFAP) can be used to identify astrocytes.
    • Glial fibrillary acid proteins (GFAP) make up intracellular intermediate filaments located in astrocytic processes.
  • Astrocytes become reactive and hypertrophic from injury, infection, or chronic neurodegeneration. Reactive hypertrophic astrocytes upregulate GFAP, proliferate, and form a glial scar that surrounds damaged CNS tissue.

Microscopic images of astrocytes

Oligodendrocytes

  • Responsible for the formation of myelin in the central nervous system
    • Myelin provides electrical insulation that allows for saltatory conduction, the speed of which is determined by the length of the internodal myelin segments. Larger axonal diameters conduct faster than smaller diameters.
  • Oligodendrocytes have condensed, rounded nuclei and unstained cytoplasm.
  • Myelinated fibers can be easily identified on microscopic slides with Luxol fast blue (LFB) staining.
    • The lack or paucity of LFB staining can suggest demyelinating disease.
  • Leukodystrophies typically involve metabolic and lysosomal pathways that are necessary for normal oligodendrocyte function.
  • Progressive Multifocal Leukoencephalopathy (PML) likely involves lytic infection of oligodendrocytes to induce demyelination.
  • Oligodendrogliomas are primary brain tumors with a classic ‘chicken wire’ appearance on histopathology.

Oligodendrocytes vs. Oligodendroglioma

Astrocyte-Oligodendrocyte crosstalk

  • Communication occurs by direct cell-cell gap junctions, as well as secreted signaling molecules.
  • The importance of astrocyte-oligodendrocyte communication is made apparent in primary astrocytopathies such as Alexander disease, and osmotic demyelination syndrome.
    • Alexander disease is a rare leukodystrophy caused by mutations in the GFAP gene. This results in an accumulation of abnormal filaments (Rosenthal fibers) in astrocytes. This leads to oligodendrocyte death and demyelination.
      • The infantile form of this disease presents with megalencephaly, seizures, spasticity, and developmental delay.
    • In osmotic demyelination syndrome, astrocyte death is observed before oligodendrocyte death and demyelination.

Ependymal cells

  • Produces and facilitates the movement of cerebrospinal fluid (CSF).
  • Lines the ventricles and central canal of the spinal cord.
  • Resembles simple cuboidal or columnar epithelium with some cilia and microvilli on histopathology.

Microglia

  • The primary immune cell of the central nervous system.
    • Responsible for antigen presentation,
    • Activates in response to tissue damage and ischemic injury. Once activated, becomes a motile, phagocytic cell (adept for neuronophagia) which forms reactive oxygen species and secretes cytokines and proteases.
  • The smallest and rarest glial cell.
  • Derived from bone marrow/monocytes and enter the CNS in the perinatal period.
    • All other glial cells and neuronal cells are derived from neural tube cells.

Neuronal cells

  • Responsible for receiving, integrating, and propagating information to other cells.
  • Contains three parts; dendrites, cell body, and axon(s).
    • Dendrites
      • Receive information from other neurons at synapses.
      • Changes in dendritic spines are critical for neural plasticity that occurs during development and learning.
    • Cell body
      • The main synthetic and trophic center of the cell, it contains the nucleus and most organelles.
      • Easily identified by a large central and euchromatic nucleus with a prominent nucleolus.
      • Basophilic clumps of polyribosomes are called Nissl bodies.
    • Axons
      • Conducts information to muscles, glands, or neurons.
      • Axons terminate at synapses.
  • There are a few named neurons to be aware of:
    • Pyramidal Cells: The prototype cerebral neuron, present in the cortex and hippocampus, with large triangular cell bodies.
    • Stellate Cells: Described as GABAergic inhibitory interneurons that control Purkinje cell activity in the cerebellum.
    • Betz Cells: Upper motor neuron cells that are the largest neurons of the cerebral cortex.
      • Betz cells are the predominant neurons affected by motor neuron disease, such as amyotrophic lateral sclerosis.
    • Purkinje cells: Large distinct neurons in the cerebellum with a prominent pink cell body and extensive dendritic tree.
      • These degenerate in various cerebellar degeneration syndromes (e.g. alcohol, chronic phenytoin use, or anti-Yo paraneoplastic syndromes).

Anatomy of the Neuron

Neuron Axon Dendrite Myelin and Nodes of Ranvier Neurology Anatomy Diagram for Board Exam Review

 

Normal neuron on a microscope specimen
Normal Neuron (arrow)
  • Most neurons contain multiple dendrites and only one axon.
  • Neurons can be easily identified with silver staining on microscopic slides which impregnate neurofilaments.
    • Intracellular neurofibrillary tangles can suggest a neurodegenerative disease such as Alzheimer’s disease.
  • When the axons of a nerve are severely damaged, Wallerian degeneration occurs.
    • Axonal fibers distal to the area of injury degenerate, while proximal fibers survive.

Neuron Action Potential

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Labeled Lumbosacral Plexus Diagram by NowYouKnowNeuro Unlabeled Lumbosacral Plexus Diagram without labels for practice exam review sheet by NowYouKnowNeuro
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Neuron Action Potential


 

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