CNS and PNS Histology

Clinical Importance

• A 14-year-old female was rushed to the emergency department with severe headache, fever, and vomiting
• Meningitis was diagnosed after noting inflammatory cells in the cerebral spinal fluid following lumbar puncture
• A likely point of damage through a pathogen is the blood-brain barrier

Key Histological Components

• The central nervous system (CNS) comprises neurons and glial cells
• The Peripheral nervous system (PNS) consists of Ganglion cells and Nerve plexuses

Central Nervous System (CNS)

• Anatomically, the CNS consists of the brain and spinal cord
• Nervous tissue in the CNS does not contain connective tissues
  • This results in a soft jelly-like consistency of brain tissues
• Histologically, the CNS consists of two cell types which are nerve cells (neurons) and glial cells

Histology and Clinical Significance

• Neurodegenerative diseases involve progressive degeneration and death of nerve cells
  • Examples include Alzheimer's and Parkinson's disease, and motor neuron disease
• Demyelinating diseases involve damage to myelin-forming cells, which can lead to a loss of effective signalling between nerve cells
  • An example is multiple sclerosis
• Stroke is damage to nerve cells due to blockage of blood vessels or bleeding
• Blood-brain barrier (BBB) damage results in disruption to the diffusion of substances from the blood into the brain

CNS Histology: Neurons

• Most neurons consist of three parts, which are dendrites, cell body, and axon
• Dendrites are specialized for receiving stimuli from the environment, sensory epithelial cells, or other neurons
• The cell body or perikaryon represents the trophic center for the whole nerve cell and is also receptive to stimuli
• The axon is a single process specialized for generating or conducting nerve impulses to other cells which include nerve, muscle or gland cells

Neurons Size and Shape

• Neurons and their processes are extremely variable in size and shape
• Multipolar neurons are the most common form, with numerous dendrites projecting from the cell body
  • An example of this is motor neurons
• Bipolar neurons have a single dendrite which arises from the pole of the cell body opposite to the origin of the axon
  • These neurons act as receptor neurons for the senses of smell, sight, and balance
• Pseudo-unipolar neurons have a single dendrite and axon that arises from a common stem of the cell body
  • An example of this consists of sensory neurons

Neuron Features

• Most neurons have a light, large nucleus with a distinct nucleolus
• The cytoplasm of many neurons contains fairly large amounts of rough endoplasmic reticulum
  • This aggregates within the cytoplasm of the neuron to form Nissl-bodies
• The feltwork of nerve fibres, neuronal and glial cell processes consists of neuropil

Clinical Significance of Neuropil.

• Clinical significance of the neuropil involves Schizophrenia and Alzheimer's disease

CNS Histology: Glial Cells

• Glial cells are non-neuronal supporting cells in the CNS
• Glial cells offer support, nutrition, repair of damaged tissue, defense, isolation of individual neurons, and phagocytosis
• Glial cells include astrocytes, oligodendrocytes, microglia, and ependymal cells

Glial Cells: Astrocytes

• Astrocytes are stellate cells (8-12µm diameter) which send their processes to surround or contact surfaces of neurons not contacted by synapses
• Astrocytes surround or contact about 99% of the brain capillary surface area
• Astrocytes help in binding neurons to capillaries, thus play an important role in maintenance of the composition of the extracellular fluid

Astrocytes Functions

• Astrocytes provide metabolic exchange that facilitates the exchange of nutrients and metabolites between neurons and blood
• Astrocytes undergo scar formation which acts as the primary scar-forming cells of the CNS after injury
• Astrocytes regulate signal propagation and control signal transmission between neurons
• They also maintain ionic and transmitter balance, ionic homeostasis, and neurotransmitter metabolism to ensure optimal neuronal function
• Astrocytes induce vascular endothelial cells to form the selective barrier that protects the brain by controlling substance entry which also consists of the blood-brain barrier

Astrocyte Clinical Significance and Therapeutic Treatment

• Astrocytoma is benign
• Glioblastoma multiforme (Glioblastoma) is malignant
• Astrocyte modulation targets astrocytic functions, glutamate uptake, and inflammatory cytokine release
  • An emerging therapeutic approach for neurodegenerative diseases, epilepsy, and stroke
• Astrocyte transplantation involves research into transplanting healthy astrocytes for CNS repair, specifically in spinal cord injury, which is ongoing

Glial Cells: Oligodendrocytes

• Oligodendrocytes produces the myelin sheath which insulates axons in the CNS, similar to Schwann cells in the PNS.
• Myelin basic protein and phospholipids consist of the major components of myelin
• Oligodendrocytes are predominant in white matter
• An oligodendrocyte sends a glial process forming compact myelin spiraling around an axon
• Each oligodendrocyte can make differing numbers of myelin segments with variable lengths along similar axon tracts

Glial Cells: Microglial cells

• Microglial cells are small, elongated, with short processes which are discovered in small amounts
• Microglial cells are phagocytic cells derived from mononuclear cells of the blood
• In the case of tissue damage, microglia can proliferate and differentiate into phagocytotic cells
• Microglial cells are macrophage-like cells that help remove cellular debris and damaged cells

Glial Cells: Ependymal cells

• Ependymal cells are low columnar ciliated cells that line the fluid-filled cavities of the CNS
• Ependymal cells transport fluid which contributes to circulation and homeostasis of cerebrospinal fluid (CSF)
• In several locations in the brain, specifically the choroid plexuses, they are specialized to produce cerebrospinal fluid (CSF)
• The lack of tight junctions between ependymal cells allows a free exchange between cerebrospinal fluid and nervous tissue

CNS Glial Cells Summary

• Glial cells are involved with CNS homeostasis and interactions with neurons
• They respond to lesions, leading to scar formation
• Glial cells may proliferate to form brain tumors which include astrocytoma and oligodendrocytoma

Clinical Significance: Histological Responses in CNS Injury/Damage

• Neurons have a limited ability to survive significant changes in their metabolic or physical environment compared to astrocytes or microglial cells
• Chromatolysis occurs when neurons undergo reversible cell damage, histologically recognizable by swelling of the cell body associated with loss of Nissl substance
  • This is seen in the cell body of a neuron after damage to the axonal process
• Necrosis of brain tissue usually results in liquefaction, leaving a fluid-filled space
• Due to lack of fibroblasts, healing through granulation tissue and fibrous scarring following an injury or necrosis is an uncommon event in the CNS
• An initial response to injury includes an exudative response with activation of local microglia and recruitment of phagocytic monocytes to phagocytose dead tissue
  • This is followed by proliferation of astrocytes to form an astrocytic scar which is also known as gliosis
• Gliosis and astrocytic scarring of the CNS is a common end product of damage to the specialized structures of CNS

Edema

• Cerebral edema involves accumulation of excess fluid within the brain parenchyma
  • Leads to a higher intracranial pressure
  • Potential neurological deficits
• Vasogenic edema involves this involves the disruption of the BBB and leads to high permeability of the vascular -Common causes is inflammation, neoplasms, abscesses, and trauma.
  • Primary Impacts white matter.
• Cytotoxic edema is swelling of neurons, glial,and endothelial cells due to the decline of the cell ion pumps due to stroke or toxins with intracellular accumulation of sodium
  • this means involves white and grey matter

Blood-brain barrier elements

• Three cellular elements of the brain microvasculature compose the BBB: endothelial, astrocyte end-feet and pericytes
• Forms a diffusion barrier that prevents blood born subtances from going through
• Endothelial cells have junctions to cerebral endoethelial cells that creates the fusion barrier, keeping many subtances outside of the brain
• Astocytic end feet maintain the tight junctions
• Drug treatment has limited affect on brain tumors because of it ability to penetrate the blood brain barrier
• Opening of the barrier has been an evolution by drugs to reach their targets
• Neurological diseases like stroke, are an affect that can disrupt the BBB barrier

Self Assessment

• For a image consisting of a MRI in a male whom suffered a blast- the cell mostly associated is the formation of astrocytic/white matter hyper-intensities known as astrocytes
• If histology shows Fried egg cells known as oligodendrocyte, could be right side temperol
• Astrocytes contributes to which of the following cell types contributes to maintenance of the blood-brain barrier?
• For cytotoxic damage and white/grey matter damage- it's cytotoxic
• Histology showing neuron and glials and capillaries