Histology of the Nervous System

• Study notes on the histology of the nervous system are presented

Structural and Functional Units

• Neurons are excitable cells that transmit impulses but don't multiply
• Neuroglia are non-excitable cells, that support and nourish neurons, and can divide

Neuropil Definition

• Any area in the nervous system, containing unmyelinated axons, dendrites, glial cell processes, and microvasculature
• Forms a synaptically dense region providing total connectivity within the local brain region

Arrangement of Grey and White Matter

• Gray matter comprises neurons, neuroglia, and neuropil
• White matter consists of myelinated axons
• In the cerebrum/cerebellum, gray matter forms the outer cortex and subcortical clusters
• White matter forms the core of the cerebrum and cerebellum
• In the brainstem, gray matter is arranged in clusters (nuclei) and in the spinal cord shaped like a butterfly
• The spinal cord and brainstem's peripheral rim consists of white matter

Nuclei and Ganglia

• Nuclei and ganglia relay afferent and efferent neurons centrally and peripherally
• Nuclei are clusters of nerve cell bodies in the CNS
• Ganglia are clusters of nerve cell bodies in the PNS

Neuron Structure

• The cell body/soma is the trophic unit
• Dendrites are receptive units
• Axons are conductive units

Perikaryon/Soma/Cell Body

• This part of the neuron encloses the nucleus and organelles required for maintenance/repair
• Contains a large, pale nucleus with noticeable nucleoli
• Cytoplasm includes RER (Nissl bodies) for protein synthesis
• The cytoplasm also contains the Golgi complex for packaging and tagging proteins, mitochondria, and lysosomes for digesting cellular debris

Cytoskeleton of Neurons

• The Neuronal cytoskeleton is made of filamentous protein complexes
• Microtubules are the largest filaments, which provide structural support and axonal transport
• Neurofilaments are intermediate filaments abundant in the axon
• Microfilaments are the smallest elements, playing a major role in axon growth and arrangement of synaptic zones

Dendrites Characteristics

• Cytoplasmic extensions (antennae) of the soma
• Neurons have multiple short dendrites, forming a dendritic tree
• Receptors for various neurotransmitters are present on the often branched structures
• Postsynaptic sites are on dendritic spines--small extensions from dendrites at a right angle--that receive signals from axon terminals

Axon Features

• Axons carry information to other neurons or muscle cells
• A single, long process with collateral branches in neurons with branched processes called telodendria
• Axoplasm lacks the RER and Golgi complex and is externally covered by axolemma
• The Axon consists of the hillock, the initial segment, the axon proper, and the terminal
• No microtubules are present in the axon terminal, instead, microfilaments support the presence of synaptic vesicles, membrane proteins, and many mitochondria
• Only Axons can become myelinated

Types of Axonal Transport

• Anterograde transports toward the axon terminal using kinesin
• It moves functional molecules (enzymes/neurotransmitters) and organelles from the soma to the axon terminal
• Soluble proteins are moved by slow anterograde transport
• Retrograde transports towards the cell body utilizing dynein
• Surplus membrane components and damaged organelles are moved for recycling
• Molecules, released by postsynaptic neuron endocytosis and transported to the cell body include growth factors such as neurotrophins
• Transport of toxins and viruses towards the neuron

Clinical Relevance of Axonal Transport

• Viruses and toxins use retrograde transport to attack the neuron soma
• Poliovirus damages motor neuron cell bodies in the spinal cord
• Tetanospasmin (from Clostridium bacteria) blocks inhibitory neurons in the spinal cord
• Disrupted axonal transport by microtubules results from neurodegenerative diseases.
• Normal microtubules transport vesicles and are stabilized by tau
• Accumulation of extra phosphate molecules leads to tau protein hyperphosphorylation resulting in the destabilization and disintegration of microtubules in Alzheimer's
• Hyperphosphorylated tau protein and axonal microfilaments form a mesh, interrupting communication between terminal and soma, resulting from transport failure
• Anterograde transport failure results in the unavailability of neurotransmitters interrupting synaptic transmission ultimately leading to failure of interneuronal communication
• Retrograde transport failure results in the accumulation of waste in the axon, neuronal death and eventually to cortical atrophy

Signs of Neuronal Degeneration

• Cell body swelling
• Loss of Nissl substance i.e. red neuron
• Shrinking and peripheral shifting of nucleus
• Apoptosis

Classification of Neurons Based on Structure

• Bipolar neurons have one dendrite-like process for sensory input and another axon-like process to transmit information to other neurons
• Pseudo-unipolar neurons are a modified form of bipolar neurons, with a single process that splits into peripheral/central processes located in the dorsal root ganglia of the spinal cord and Trigeminal ganglion
• Multipolar neurons, common in the CNS, each contain abundant dendrites and single axon

Multipolar Neuron Recognition

• Multipolar neurons in specific locations might have specific shapes
• Some neurons show distinguishing arborization / branching patterns
• Purkinje neurons are in the cerebellar cortex
• Pyramidal neurons are located in the cerebral cortex

Functional Classes of Neurons

• Sensory/afferent neurons carry body system information via the brainstem and spinal cord
• Motor/efferent neurons transmit commands via the brainstem and spinal cord
• Interneurons connect different brain areas, facilitating communication between cortical and subcortical gray matter

Neuron Communication

• A neuronal synapse at the area close to another neuron, serves as a communication site
• Based on structure, synapses include axo-dendritic, axo-somatic, axo-axonic, and dendro-dendritic types
• Synapses can be glutaminergic (excitatory) or GABAergic (inhibitory)

Neuroglia Definition

• Neuroglia are nerve glue
• Distinguishable due to smaller size compared to neurons, they outnumber neurons 9:1 in the CNS

CNS and PNS Neuroglia

• CNS neuroglia: astrocytes, microglia, oligodendrocytes, and ependymal cells
• PNS neuroglia: satellite and Schwann cells

Astrocytes Description

• Astrocytes are star-shaped cells derived from neuroepithelium
• These glial cells are the most abundant and also the largest
• Astrocytes guide neuronal migration (radial glia) during development; regulate extracellular composition/take up K+ ions after activity
• In the synthesis, astrocytes absorb and recycle neurotransmitters and proliferate after CNS damage
• They contain GFAP intermediate filaments serving as an aging/brain damage marker
• Both blood vessels and synapses contact astrocytes, titrating blood flow relative to levels of synaptic action

Types of Astrocytes

• Protoplasmic astrocytes in gray matter have abundant short processes providing metabolic support and also involved in BBB formation
• Fibrillar astrocytes reside in the white matter, with long processes predominantly assisting scar development inside the PNS/CNS
• GFAP maintains astrocyte integrity and assists its shape and movement; GFAP integrity is crucial to BBB integrity
• Elevated GFAP expression corresponds to astrocyte activation and gliosis during neurodegeneration

Oligodendrocytes Definition

• Derived from neuroepithelial origin
• Small cells with darkly stained nucleus and a clear zone around nucleus, and myelinate axons within the CNS
• One oligodendrocyte forms myelin sheaths on several axons

Ependymal Cells Definition

• The neuroepithelial-derived ependymal cells line the ventricles/spinal cord and aid cerebrospinal fluid synthesis

Microglia Definition

• Small, spindle-shaped mesodermal-origin cells that transform into phagocytes within the CNS and release cytokines. Activated microglia release IL-1, IL-6, and TNF-a.
• Activated microglia may limit further damage to neurons via IL-6 or worsen neurodegenerative conditions

Choroid Plexus Definition

• These vasculoepithelial brain structures produce cerebrospinal fluid with tela choroidae (fenestrated capillaries loops wrapped in pia mater)
• Choroid plexus' include ependymal cells resting on the basement membrane of capillaries which allows it to contain tight functions that is crucial to its function

Natural Protective Mechanism

• The natural defense of the central nervous system includes continuous capillaries, tight junctions, basement membranes, and astrocyte foot processes, which altogether constitute the blood-brain barrier
• No paracellular and transcellular transport occurs due to the natural defenses
• This barrier maintains a constant internal milieu in the brain, unaffected by homeostasis fluctuations
• The BBB is not developed at birth, so the brain is vulnerable to pathological events during infancy
• The BBB can be breached under hypertension, hyperosmolality, infection, trauma, ischemia, radiation, and raised intracranial pressure

Circumventricular Organs Definition

• Specialized brain structures located around the ventricular system lacking a blood-brain barrier include the area postrema, pineal body, subcommissural organ, subfornical organ, organum vasculosum lamina terminalis (OVLT), neurohypophysis, and median eminence

PNS Neuroglia

• Neural crest-derived Schwann cells myelinate axons in the PNS needing multiple cells to support the peripheral nerves
• Satellite cells: neural crest-derived and small/flattened. They are found in the ganglia of the peripheral nervous system, wrapping around neuron somas and stabilizing the environment of the ganglia

Myelination Functions

• Protects and electrically insulates the fibers and increases nerve conduction velocities.
• The gap between the membranes is denoted to as Nodes of Ranvier.
• In the CNS, oligodendrocytes are responsible for CNS myelination. One oligodendrocyte myelinates multiple axons
• In the PNS, myelination is a Schwann cell duty that myelinate a single axon

Layers of Typical Peripheral Nerve

• Epineurium covers the bundles
• Perineurium covers individual bundles
• Innermost endoneurium covers individual axons

Clinical Relevance of Peripheral Nerve Injury

• Neuropraxia results from conduction block as a consequence of compression
• Axonotmesis defines axonal damage
• Neurotmesis defines when the nerve is severed

Consequences of Axonal Damage

• Wallerian degeneration is the active consequences of severed nerves and occur 7 to 21 days after the injury
• Proximal segment changes occur when broken segments degrade or die within the span until the final portion
• Distal segment changes occur with myelin and axonal degradation as well as release of chemotactic factors after Schwann activations occurs leading to macrophages leading to the removal of debris

Axonal Regeneration

• When adult neurons survive, axonal repair is possible, but only if there isn't an astrocytic response, because they form barrier
• PNS axon regeneration is possible as long as the system is still intact and may grow up to 2 to 4 mm/day

Explore the histology of the nervous system, including neurons, neuroglia, and neuropil. Understand the arrangement of gray and white matter in the cerebrum, cerebellum, brainstem, and spinal cord. Learn about the structural and functional units that enable nerve impulse transmission and support.