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Histology of the Brain

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1. Neurons - The Structural and Functional Unit

Classification of Neurons

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2. The Neuron Cell Body (Perikaryon)

• Large euchromatic nucleus with a prominent nucleolus (reflects intense protein synthesis)
• Nissl bodies - basophilic granules seen with basic dyes (e.g., cresyl violet, thionine); each Nissl body corresponds to a stack of rough endoplasmic reticulum (rER) + free ribosomes. They extend into dendrites but not into the axon
• Golgi apparatus - large, perinuclear
• Mitochondria, lysosomes, neurofilaments (intermediate filaments), neurotubules (microtubules), and transport vesicles

Axon Hillock

• The region where the axon originates from the cell body
• Lacks Nissl bodies and Golgi cisternae - distinguishes axons from dendrites histologically
• Site of MTOC (centrosome)
• The Axon Initial Segment (AIS) follows immediately after the hillock - this is where action potentials are generated

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3. Dendrites and Dendritic Spines

• Dendrites transmit impulses toward the cell body; they contain Nissl bodies, free ribosomes, and Golgi apparatus
• Dendritic spines are short protrusions on dendrites, especially on pyramidal neurons; they are the primary sites of excitatory synapses
• Spines are dynamic structures: their density increases with learning and memory acquisition; stable spines can persist for months
• Loss of dendritic spines on pyramidal neurons in the DLPFC is implicated in schizophrenia

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4. Axon

• Conducts impulses away from the cell body
• One axon per neuron; can be over a meter long (e.g., motor neurons)
• Cytoplasm (axoplasm) contains microtubules, neurofilaments, mitochondria, and transport vesicles - but NO Nissl bodies
• Anterograde transport (cell body → terminal): kinesin-driven, fast (200-400 mm/day) or slow (0.5-5 mm/day)
• Retrograde transport (terminal → cell body): dynein-driven; used by viruses (herpes, rabies) and toxins to enter the CNS

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5. Synapses

• Presynaptic knob - contains synaptic vesicles loaded with neurotransmitter
• Synaptic cleft - 20-30 nm gap
• Postsynaptic density - complex of interlinked proteins anchoring receptors and signal transduction machinery

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6. Neuroglia (Supporting Cells of the CNS)

Key contrast: In the PNS, myelin is produced by Schwann cells (each cell myelinates only one axon segment). In the CNS, myelin is produced by oligodendrocytes.

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7. Cerebral Cortex - Layered Architecture

Two Major Neuron Types in Neocortex

• Triangular cell body with a single apical dendrite ascending to the cortical surface
• Basal dendrites spread laterally
• Dendritic spines carry most excitatory synapses
• Predominantly excitatory (glutamate); projection neurons

• Small local circuit neurons (interneurons)
• Primarily inhibitory (GABA)
• Multiple subtypes distinguished by neuropeptide content and morphology: chandelier cells, basket cells, Martinotti cells, double-bouquet cells
• Axons arborize locally within gray matter

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8. Gray Matter vs. White Matter

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9. Key Histological Stains for Brain Tissue

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• Histology: A Text and Atlas with Correlated Cell and Molecular Biology (9781975181512), Chapter 12 - The Neuron, pp. 908-940
• Kaplan & Sadock's Comprehensive Textbook of Psychiatry (9781975175733), pp. 210-218 - Cerebral Cortex

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Spinal Cord: Histology and Clinical Lesion Syndromes

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Part 1 - Histology of the Spinal Cord

Gross Organization

• Inner butterfly/H-shaped gray matter - contains neuron cell bodies, dendrites, synapses, and neuroglia
• Outer white matter - contains ascending and descending myelinated axon tracts

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Gray Matter

Anterior Horn Cells (Motor Neurons)

• Large, basophilic multipolar neurons - easily recognized on H&E
• Prominent Nissl bodies in cytoplasm
• Large euchromatic nucleus with prominent nucleolus
• Axon exits via the ventral root → spinal nerve → neuromuscular junction

Dorsal Horn

• Receives pseudounipolar sensory neurons whose cell bodies lie in dorsal root ganglia (DRG)
• Contains substantia gelatinosa (Rexed lamina II) - small neurons processing pain/temperature
• Central segment of DRG neurons enters posterior horn via dorsal root

Rexed's Laminae (I-X)

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White Matter - Funiculi and Tracts

Ascending (Sensory) Tracts

• Location: Posterior funiculus
• Tracts: Fasciculus gracilis (lower limb/trunk) + Fasciculus cuneatus (upper limb/neck)
• Modalities: Fine touch, vibration, conscious proprioception, 2-point discrimination
• Course: 1st order neuron enters ipsilateral posterior column → ascends to medulla → crosses (internal arcuate fibers) → medial lemniscus → VPL thalamus → primary somatosensory cortex
• Ipsilateral until medulla - lesions below medulla cause ipsilateral loss

• Location: Anterior and lateral funiculus
• Modalities: Pain, temperature, crude touch
• Course: 1st order neuron enters posterior horn (laminae I, IV, V) → crosses in anterior white commissure (2-3 segments above entry) → ascends contralateral anterolateral column → VPL thalamus → somatosensory cortex
• Crosses within spinal cord - lesions cause contralateral loss below injury level

• Dorsal (posterior) spinocerebellar: Ipsilateral; unconscious proprioception from lower limb
• Ventral (anterior) spinocerebellar: Crossed then re-crossed; unconscious proprioception

Descending (Motor) Tracts

• Location: Lateral funiculus (lateral white matter)
• Origin: Primary motor cortex (Betz cells, layer V)
• Course: Motor cortex → corona radiata → posterior limb internal capsule → crus cerebri → pons → crosses in pyramidal decussation at medulla-cord junction → descends ipsilateral lateral column → synapse on anterior horn cells
• Function: Voluntary movement of limbs (especially distal fine movements)
• Lesion above decussation → contralateral UMN signs; lesion in cord → ipsilateral UMN signs

• Uncrossed; descends in anterior funiculus; controls axial/trunk muscles

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Meninges

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Part 2 - Spinal Cord Lesion Syndromes

Key Principle: Tract Localization

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1. Complete Cord Transection

• Complete bilateral motor loss (UMN if above conus; LMN at level of lesion)
• Complete bilateral loss of all sensory modalities
• Autonomic dysfunction: neurogenic bladder/bowel, loss of sweating
• Acute: Spinal shock - flaccid paralysis, areflexia, urinary retention
• Chronic: Spasticity, hyperreflexia, Babinski sign

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2. Brown-Séquard Syndrome (Hemisection)

Prognosis is good - best recovery of all incomplete cord syndromes.

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3. Central Cord Syndrome

• Upper limbs > lower limbs weakness (central fibers of corticospinal tract serving arms are most affected)
• Greater distal > proximal dysfunction in arms
• Variable sensory loss
• Sacral pinprick sensation often preserved (sacral fibers are peripheral in cord)
• Bladder dysfunction common

Most common incomplete cord syndrome. Prognosis is moderate - >50% regain ambulation.

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4. Anterior Cord Syndrome

• Complete motor loss below lesion (bilateral)
• Loss of pain and temperature below lesion (bilateral)
• Preserved: Vibration, proprioception, fine touch (posterior columns intact)

Worst prognosis of all incomplete cord syndromes.

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5. Posterior Cord Syndrome

• Loss of proprioception and vibration (bilateral)
• Preserved: Motor function, pain, temperature
• Presents as sensory ataxia (positive Romberg test)

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6. Conus Medullaris Syndrome

• Mixed UMN + LMN picture (sacral LMN + lumbar UMN)
• Areflexic bladder (urinary retention → overflow incontinence)
• Areflexic bowel (fecal incontinence)
• Saddle anesthesia (perineum, genitalia)
• Erectile dysfunction
• Loss of bulbocavernosus reflex and anal wink = poor prognosis

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7. Cauda Equina Syndrome

• Flaccid, areflexic paralysis of lower limbs
• Saddle anesthesia
• Areflexic bladder and bowel
• Absent lower limb reflexes
• Often asymmetric (roots affected unevenly)
• Surgical emergency - early decompression needed

Cauda equina vs conus: Both cause saddle anesthesia and bladder/bowel dysfunction. Cauda equina is pure LMN (flaccid, areflexic). Conus has mixed UMN+LMN features.

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Quick Reference: Lesion Pattern Summary

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• Histology: A Text and Atlas (9781975181512), Chapter 12, pp. 998-1010
• Gray's Anatomy for Students (9780323934237), Chapter 9, pp. 1325-1330
• Campbell's Operative Orthopaedics 15th Ed (9780443117633), Chapter 48, pp. 2468-2472
• Bradley and Daroff's Neurology in Clinical Practice (9780323642613), Spinal Cord Injury Syndromes