Review
The axon as a physical structure in health and acute trauma

https://doi.org/10.1016/j.jchemneu.2016.05.006Get rights and content

Highlights

  • Cytoskeletal components and internal structure of the axon are reviewed in detail.

  • Current theories of neurofilament interactions are used to reconceptualise their role.

  • The internal cytoskeleton is mechanically linked to the extracellular environment.

  • These properties are considered in a discussion of forces acting in acute trauma.

Abstract

The physical structure of neurons – dendrites converging on the soma, with an axon conveying activity to distant locations – is uniquely tied to their function. To perform their role, axons need to maintain structural precision in the soft, gelatinous environment of the central nervous system and the dynamic, flexible paths of nerves in the periphery. This requires close mechanical coupling between axons and the surrounding tissue, as well as an elastic, robust axoplasm resistant to pinching and flattening, and capable of sustaining transport despite physical distortion. These mechanical properties arise primarily from the properties of the internal cytoskeleton, coupled to the axonal membrane and the extracellular matrix. In particular, the two large constituents of the internal cytoskeleton, microtubules and neurofilaments, are braced against each other and flexibly interlinked by specialised proteins. Recent evidence suggests that the primary function of neurofilament sidearms is to structure the axoplasm into a linearly organised, elastic gel. This provides support and structure to the contents of axons in peripheral nerves subject to bending, protecting the relatively brittle microtubule bundles and maintaining them as transport conduits. Furthermore, a substantial proportion of axons are myelinated, and this thick jacket of membrane wrappings alters the form, function and internal composition of the axons to which it is applied. Together these structures determine the physical properties and integrity of neural tissue, both under conditions of normal movement, and in response to physical trauma. The effects of traumatic injury are directly dependent on the physical properties of neural tissue, especially axons, and because of axons’ extreme structural specialisation, post-traumatic effects are usually characterised by particular modes of axonal damage. The physical realities of axons in neural tissue are integral to both normal function and their response to injury, and require specific consideration in evaluating research models of neurotrauma.

Section snippets

The axon

In the mature nervous system, the primary purpose of the axon is to propagate and regenerate action potentials at a consistent speed, and secondarily to this, to provide support for the energetic and signalling needs of its distal processes. Accordingly, its interior is structured to maintain its shape and calibre, and permit rapid internal transport along its length, while remaining compliant across the range of everyday movements. In large part this is attributable to the physical qualities

Extracellular matrix and surface ligands

During development, axons are formed by growth cones navigating through tissue, generating mechanical traction by means of adhesions with the extracellular matrix and other cells (O’Toole et al., 2008, Haynes and Kinney, 2011, Dent et al., 2011). These interactions determine axonal morphology, and the shape of the axon reflects a balance between internal cytoskeletal tension and the external physical environment (Bauer and ffrench-Constant, 2009). Many extracellular molecules link with proteins

Mechanical properties of CNS tissue

The brain and spinal cord are extremely soft tissues, which in vivo are suspended by arachnoid trabeculae, and float in cerebrospinal fluid. Accordingly, their mechanical properties as bulk tissue in vivo have proven difficult to measure; Meaney et al. (2014) observe that recent measurements using sensitive techniques suggest that neural tissue is an order of magnitude softer than widely cited measurements made in the 1970s to 2000s. In bulk, living neural tissue has unusual nonlinear

Normal movement

The physical environment in which axons must operate differs significantly between the CNS and the PNS. In the CNS, the surrounding tissue is more static and mechanically isolated from physical movement by arachnoid trabeculae and CSF cushioning (Meaney et al., 2014). The only major movements experienced inside the blood-brain barrier are flexions and torsions of bulk tissue, such as bending of the spinal cord within the vertebral column, rotation of the head (turning the brain with respect to

Conclusion

Popular science illustrations show neurons floating in the void, touching only at synapses. The reality is almost completely the opposite − in the CNS and peripheral nerves, every micron of the surface of the soma, dendrites and axons is physically coupled to other neurons, glia, ependymal cells, extracellular matrix or basal lamina. This tight integration, and its crosstalk with the internal cytoskeleton, is fundamental to the function and physical properties of neurons. Nowhere is this more

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