CNS Histology and Pathology Part 1

Overview: CNS Histology and Pathology - Part 1

• This lecture provides an overview of the histology and pathology of the central nervous system (CNS).
• Diagrams and photos are sourced from "Atlas of Functional Histology" by Jeffrey B Kerr, "Wheater's Functional Histology", and "Blue Histology (online)" from the University of Western Australia.

Clinical Importance: Meningitis Case

• A 14-year-old female was admitted to the emergency department with severe headache, fever, and vomiting.
• The diagnosis was meningitis, based on the presence of inflammatory cells in the cerebral spinal fluid obtained via lumbar puncture.
• The cellular components most likely to be damaged by the pathogen are:
  • Endothelial cells
  • Astrocytes
  • Pericytes

Key Histological Components of the Nervous System

• The central nervous system (CNS) mainly comprises neurons and glial cells (non-neuronal cells).
• The peripheral nervous system (PNS) consists of ganglion cells and nerve plexuses.

The Central Nervous System (CNS)

Options include:

• The CNS anatomically includes the brain and spinal cord.
• The nervous tissue of the CNS lacks connective tissues, giving it a soft, jelly-like consistency.
  • This is why there is no scar tissue from collagen
  • There are scars from something called gliosis
• Histologically, the CNS consists of two main cell types: nerve cells (neurons) and glial cells.

Histology and Clinical Significance: CNS Diseases

• Examples of neurodegenerative disorders:
  • Alzheimer's disease
  • Parkinson's disease
  • Motor neuron disease
  • All involve progressive degeneration and death of nerve cells.
• Demyelinating diseases involve damage to insulating myelin forming cells.
  • This leads to impaired nerve signal transmission
  • An example is multiple sclerosis.
• Glial cells secrete myelin
• Damage to brain nerve cells can be caused by blockage of blood vessels or bleeding – a stroke.
• Damage to the blood-brain barrier (BBB) disrupts substance diffusion into the brain, preventing certain drugs from entering.

Histology of Neurons within the CNS

• Neurons consist of three parts:
  • Dendrites which are specialized for receiving external stimuli
  • Cell body (perikaryon), containing the trophic center for the whole nerve cell
  • Axon, a single process specialized for generating/conducting nerve impulses to other cells.
• Neurons vary greatly in morphology

Types of Neurons

• Neurons come in many sizes and shapes.
• Multipolar neurons are the most common form, characterized by numerous dendrites projecting from the cell body; motor neurons are an example.
• Bipolar neurons have a single dendrite arising from the cell body opposite the axon's origin, functioning as receptor neurons for senses like smell and sight; examples include olfactory neurons.
• Pseudo-unipolar neurons feature a single dendrite and axon arising from a common stem of the cell body, typically acting as sensory neurons.

Microscopic Features of Neurons

• Most neurons have a light, large nucleus with a distinct nucleolus.
• The cytoplasm contains significant amounts of rough endoplasmic reticulum, forming Nissl bodies.
• The feltwork of neuronal and glial cell processes is the neuropil.
• Change of expression of proteins happen in the Neurpil.
• The clinical significance of neuropil relates to Schizophrenia and Alzheimer's disease.
  • Astocyte scar is related to gliosis
  • Inflammatory-encephalitis

Glial Cells in the CNS

• Glial cells provide support in the CNS.
• Glial cells are non-neuronal cells
• They offer support, nutrition, repair, defense, and isolation for neurons.
• Glial cells include:
  • Astrocytes
  • Oligodendrocytes
  • Microglia
  • Ependymal cells

Astrocytes

• These are stellate cells, 8-12µm in diameter, that contact neuron surfaces not contacted by synapses.
• Astrocytes cover about 99% of the brain capillary surface area.
• They bind neurons to capillaries for extracellular fluid maintenance.
  • These hold up blood vessels - capillaries

Astrocyte Functions

• Specific functions include;
  • scar*-forming cells of the CNS.
  • Control of signal propagation between neurons;
  • Maintenance of ionic and transmitter metabolism; and
  • Induction of vascular endothelial cells to form a seal or selective filter, called the blood – brain barrier.

Clinical Significance of Astrocytes

• Astrocytoma is benign
• Glioblastoma Multiforme- Malignant
• Astrocyte modulation with therapeutic potential works by targeting astrocytic functions for neurodegenerative diseases, stroke and epilepsy.
• There is ongoing research on astrocyte transplantation for CNS repair in spinal cord injury.

Oligodendrocytes

• These produce the myelin sheath for axon insulation in the CNS, similar to Schwann cells in the PNS.
• Myelin consists mainly of myelin basic protein and phospholipids.
• Oligodendrocytes are predominant in white matter.
• One oligodendrocyte sends out glial processes forming forming compact myelin around an axon.

Identifying Oligodendrocytes Under a Microscope

• Look for a White halo, or peri-nuclear halo which will give a fried-egg appearance
• Should be areas with little to no inflammation

Microglial Cells

• These are small, elongated cells with short processes, found in small numbers with
• They are phagocytic cells derived from mononuclear blood cells.
• They can proliferate and differentiate after tissue damage.
• They act as macrophage like cells in the CNS to remove cellular debris and damaged cells.

Glial Cells: Identification

• Glial cell nuclei are observed in relatively small numbers.
• Immunochemical staining identifies microglial cell activity.

Ependymal Cells

• These are Low columnar cells that line the fluid filled cavities of the CNS.
• Ependymal cells are ciliated
• They transport fluid
• In the choroid plexus they produce cerebrospinal fluid.
• A lack of tight junctions allows free exchange between cerebrospinal fluid and nervous tissue.

Summary of Glial Cells

• Glial cells maintain CNS homeostasis and interact with neurons.
• Glial cells respond to lesions for repair
• Glial cells proliferate and can form tumors

Histological Responses in CNS Injury

• Neurons are less robust/adaptable than astrocytes or microglial cells in response to injury.
• Chromatolysis refers to neurons undergoing reversible cell damage which results in them becoming recognizable histologically because of swelling of the cell body associated with loss of Nissl substance
• Necrosis in brain tissue usually results in liquefaction of damaged tissues.
• An initial response is exudative. There will be there activation of local microglia and recruitment of phagocytic monocytes.
• Astrocytic scar is a common end product to damage to the specialised structures of the CNS.

The Impact of Brain Injuries

• Lack of Fibroblasts stops healing through granulation tissue so, results in fibrous scarring
• An exudative response activates local microglia
• An astrocytic scar may form.
• Reactive changes with inflammation, Cerebral oedema can occur.

Cerebral Edema

• Swelling of neurons, glial cells, and endothelial cells occurs due to failure of cellular ion pumps.
• The swelling of neurons or glial cells due to injuries or toxins is "Cytotoxic "
• Protein and fluid leakage from vessel permeability is "Vasogenic"
  • Lesions will be localized in Cerebral edema.
• The surfaces of the gyri look flattened due to the expansion of the brain

Blood-Brain Barrier Explained

• It is composed of: endothelial cells, astrocyte end-feet, and pericytes.
• Endothelial cells are connected via tight junctions for excluding blood borne substances
• Astrocytic endfeet tightly enshorth the vessel wall and ensheath the vessel wall.
• Pericytes surround endothelial cells.

The Blood-Brain Barrier: Structure and Function

• Normal capillaries have fenestrations with an intact basal membrane, enabling selective transfer of metabolites.
• They connect Via Tight junctions
• The BBB contains intercellular space
• Blood-brain barrier (BBB): Composed of endothelial cells, astrocyte foot processes, and pericytes held together by the tight junctions .
• Astrocytes can also between the capillaries

BBB Clinical Implications

• An estimated 98% of drugs can't penetrate the BBB to treat diseases.
• Researchers temporarily open the BBB for drug delivery.
• BBB impairment complicates neurological diseases like stroke and neuroinflammatory disorders.

Brain-Histology

• Spinal cord has a white matter and gray matter.
• Glial cells are shown in both the white matter and gray matter
• Neuron Somata are shown in the gray matter

Brain Histology: Cerebral Cortex

• Pyramidal neurons are identified the character of basophilic(blue) and located in cytoplasm.
• Large nuclei and prominent nucleoli shown the charateristics of neuron

Brain Histology: Cerebellum

• The white matter inside is the medulla with plenty of neurons in the grey matter around.
• Three layers compose cerebellum which include outer molecular layer, purkinje cell layer and Inner Granular Layer.

Cerebellum Cell types

• The molecular layer: this dendrites occupy most of the layer
• Cerebellar granule cells account for half of the neurons in the CNS.

Self Assessment 1

• Microglial cells plays a signicant role in MRI hyperintensities, which is indicative of brain scars

Self Assessment 2

• Oligodendrocytes are indicated in fired egg from a 40 year old woman.

Self Assessment 3

• Astrocyte contributes in maintenance of the blood-brain barrier

Self Assessment 4

• In Cytotoxic oedea There is no white/grey matter differentiation

Self Assessment 5

• Some breakdown of chromatin is shown in the Astrocytic scar

Self Assessment 6

• Neurons, Glial cells and capillaries show features in Histology