Neuromuscular

Axon Regeneration: Peripheral Nerve

Axons
  Regeneration
  Sprouts
  Post-regeneration
    Regenerated Axon Clusters
    Thin myelination
Schwann cells
  Pseudo-onion bulb
Muscle pathology
  Fiber type groups
  Regenerated motor axon
Also see
  Collateral Sprouting

Regenerated Axon Clusters


Toluidine blue stain
Regenerating Axon Clusters (Arrow)
  Clusters of 2 to 12 axons
  Myelin thickness
    Thin for axon size
    Similar for all axons in cluster
  Associated axon loss: Features
    Reduced numbers of large & small myelinated axons
    Büngner band development
  Fibroblast processes
    May surround regenerated axon clusters
  Clusters of regenerating axons often occur with: Chronic changes in muscle
    Partial denervation
    Fiber type grouping

Regenerating Clusters


From: R Schmidt
Regenerated axons: Ultrastructure
  Cluster of 3 intermediated-sized regenerated axons with similarly thin myelin sheaths
  3 Unmyelinated small singleton axons are present (Left & Botom right)
  Small Büngner bands with clusters of small Schwann cell process )Bottom left)

Regenerating Clusters
  Pairs of axons within Schwann cell bands (Above & Below)
    Also see: Pseudo-onion bulbs
  Empty Büngner (Schwann cell) bands (Below)
    Composed of multiple interdigitated Schwann cell processes
    Axons are absent

Fibroblast Processes
  Long, branched, dark fibroblast process surrounds a regenerated axon cluster & Some collagen
Regenerated Axon Cluster
  Two thinly myelinated axons
    Surrounded by clusters of Schwann cell processes
      Previously Büngner bands
      Unmyelinated axons: Present within clusters of Schwann cell processes

Regenerating Cluster: Late
  All axons in cluster (Arrow) have nearly normal myelin sheath thickness


Toluidine blue stain

Ultrastructure: From Robert E Schmidt MD



Toluidine blue stain
Regenerating Clusters
  Thinly myelinated large axons have similar degrees of myelination
  One Schwann cell contains a large Pi granule


POST-REGENERATION
  Regenerated axons
    Usually thinly myelinated with short internodal length
    May be distributed individually (Above), or in clusters (Below)
  Thinly myelinated large axons may comprise: Most myelinated axons in a nerve
  A few myelin ovoids (Arrow head) or thickly myelined axons (Arrow) remain (Below)

POST-REGENERATION
  Regenerated axons
    Usually thinly myelinated with short internodal length
    May be distributed individually (Above), or in clusters (Below)
  Thinly myelinated large axons may comprise: Most myelinated axons in a nerve
POST-REGENERATION
  Regenerated axons
    Size: Small
    Distribution: Present in clusters

POST-REGENERATION
  Myelin around Regenerated axons
    Myelin sheaths (Below): Contain both P0 & MBP (Yellow)
      Differs from myelin around normal smaller myelinated axons which contains mainly P0

P0 green; Myelin Basic Protein (MBP) (Red); Both Yellow


P0 (Red); Neurofilament stained axons (Green); Both Yellow
POST-REGENERATION
  MBP-containing Myelin around Regenerated axons
    Most MBP-containing myelin sheaths
      Surround small, rather than large, axons
      Are smaller than in control nerves
    See: MBP myelin in control nerve, mostly associated with larger axons

P0 (Red); Neurofilament stained axons (Green); Both Yellow


Toluidine blue stain
POST-REGENERATION
  Axons: Thinly myelinated, Some in small clusters


Toluidine blue stain
  Regenerated axons
    Diffusely distributed in most of nerve (Above)
      Many thinly myelinated large & small axons
    Regenerated clusters
      Groups of Small & Large thinly myelinated axons (Above; Arrow)
    Scattered (Below; Dark Arrows): Thinly myelinated axons among larger axons with thicker myelin
  Myelinated axons: Reduced numbers

Toluidine blue stain: From Chunyu Cai
Thinly myelinated large axons: Scattered or Clustered

Toluidine blue stains of plastic nerve sections


Post-Regeneration: Few thickly myelinated large axons

VvG stain

POST-REGENERATION: Reduced numbers of large axons

Neurofilament stain

POST-REGENERATION
  Proliferation of non-myelinating Schwann cells
    Non-myelinating Schwann cells distributed all through endoneurium
  NCAM staining of myelin sheaths around regenerated axons (Arrow)
    NCAM is not usually present in normal adult myelin

NCAM stain

POST-REGENERATION
  NCAM staining of myelin sheaths

NCAM stain

Onion Bulb-like structures (Dark Arrow) & Redundant Schwann cell processes (White arrow) around thinly myelinated axons

Pseudo Onion bulb
  Center: Thinly myelinated large axon
  Surround: Multiple circumferential clusters of interdigitated Schwann cell processes

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9/23/2025