🧠 Neuron structure & polarity
Neurons are functionally polarized cells: information flows from dendrites → cell body → axon → synaptic terminals. Classification by process number:
- Multipolar (most common): one axon, multiple dendrites (e.g., motor neurons).
- Bipolar: one axon, one dendrite (retina, olfactory epithelium).
- Unipolar (pseudounipolar): single process that bifurcates (sensory ganglia).
Nissl substance = rough ER + polyribosomes. Abundant in cell body and proximal dendrites; absent from axon hillock and axon. Stains basophilic.
Clinical Lewy bodies (α-synuclein aggregates) in substantia nigra pars compacta → Parkinson disease. Negri bodies (eosinophilic inclusions) in hippocampal/cerebellar neurons → rabies.
🔬 Cytoskeleton
- Neurofilaments (intermediate filaments): structural support, abundant in axons and proximal dendrites.
- Microfilaments (actin): concentrated in growth cones and dendritic spines; involved in synaptic plasticity.
- Microtubules: tracks for axonal transport; composed of tubulin dimers.
🚄 Axonal transport
Anterograde (cell body → terminal)
- Fast (200–400 mm/day): vesicles, mitochondria, neurotransmitters. Requires microtubules + kinesin (ATPase).
- Slow (1–2 mm/day): cytoskeletal proteins, enzymes, soluble components. Microtubule-independent.
Retrograde (terminal → cell body)
- 60–100 mm/day, microtubule-dependent, uses dynein (ATPase).
- Transports trophic factors, recycled materials, and pathogens (herpes, rabies, tetanus toxin).
High yield Disruption of fast anterograde transport → axonal polyneuropathy. Causes: hypoxia, colchicine, vinblastine (microtubule depolymerization). Diabetic hyperglycemia alters microtubule proteins → distal "glove-stocking" neuropathy.
🧬 Glial & supporting cells
CNS glia
- Astrocytes: most abundant; GFAP filaments; regulate glutamate/K⁺; form glial limitans; contribute to BBB; reactive gliosis after injury.
- Oligodendrocytes: myelinate multiple CNS axons (each process wraps one internode).
- Microglia: bone marrow–derived (monocytes); immune surveillance; phagocytosis; HIV-1 reservoir; secrete cytokines and free radicals.
- Ependymal cells: line ventricles; ciliated; choroid plexus produces CSF.
- Radial glia: guide neuronal migration during development; astrocyte precursors.
PNS glia
- Schwann cells: myelinate single internode of one axon; also envelop unmyelinated axons; phagocytic after injury; guide regeneration.
Note Oligodendrocytes (CNS) vs. Schwann cells (PNS) – both form myelin, but Schwann cells are 1:1, oligodendrocytes are 1:many.
🧪 Disorders of myelination
| Disease | Key features | Pathology/notes |
|---|---|---|
| Multiple sclerosis (MS) | Relapsing-remitting; optic neuritis; INO (MLF); motor/sensory deficits; vertigo; neuropsychiatric symptoms. | Periventricular demyelinated plaques; oligoclonal IgG bands in CSF; 2:1 female predominance; onset 20–40 y. |
| Guillain-Barré syndrome | Acute ascending symmetric weakness; lower limbs → respiratory failure; autonomic dysfunction; cranial nerve involvement. | PNS demyelination; albuminocytologic dissociation (high protein, normal cells); often post-infection; reflexes reduced/absent. |
Treatment MS: high-dose steroids (acute), interferon-β, glatiramer acetate. GBS: IVIG or plasmapheresis.
🩸 Blood–brain barrier (BBB)
- Components: capillary endothelial cells (tight junctions), basal lamina, astrocyte end-feet, pericytes.
- Permeability: lipid-soluble substances (heroin, ethanol, nicotine, O₂, CO₂) diffuse freely; glucose, amino acids, vitamins K/D are selectively transported; ions via channels.
⚡ Axonal injury & regeneration
Wallerian degeneration
Distal to axotomy: axon and myelin degenerate. In PNS, Schwann cell basal lamina remains as a scaffold; regeneration ~1–2 mm/day (slow anterograde rate).
Chromatolysis
Cell body response: Nissl substance disperses, soma swells, nuclei eccentrically placed. Indicates increased protein synthesis for regeneration.
Pearl Proximal lesions (near cell body) → higher chance of neuronal death. PNS regeneration is successful only if the endoneurial sheath is intact.
🧫 Primary CNS tumors (selected)
| Tumor | Features | Histology |
|---|---|---|
| Schwannoma | CN VIII (vestibular) at cerebellopontine angle; hearing loss, tinnitus, CN V/VII signs; bilateral → NF2. | Antoni A (cellular) and Antoni B (myxoid) areas. |
| Craniopharyngioma | Children/young adults; calcified; suprasellar; compresses optic chiasm/pituitary stalk. | Ameloblastoma-like epithelium (Rathke pouch remnants). |
Metastases account for ~50% of brain tumors in adults.
- Nodes of Ranvier enable saltatory conduction → faster action potential propagation.
- Schwann cells (PNS) vs oligodendrocytes (CNS): both form myelin but differ in ratio and regenerative capacity.
- Retrograde transport is used by pathogens (rabies, herpes, tetanus) – important for pathogenesis.
- Astrocytes contribute to BBB via end-feet; microglia are immune-competent and can release neurotoxic radicals.
- MS = CNS demyelination; GBS = PNS demyelination (acute ascending).
Axon injury
→
Wallerian degeneration (distal)
→
PNS: Schwann cells + basal lamina remain → regeneration
CNS: oligodendrocytes do not support regeneration; glial scar forms