Anatomy of Peripheral Nerves, Neuromuscular Junctions, and Skeletal Muscles

After exiting the spinal cord, individual nerve roots coalesce into plexi and peripheral nerves that innervate muscle and skin. Clinical localization requires a working knowledge of this anatomy. By evaluating the distribution of muscle weakness, sensory loss, and reflexes, it is often possible to localize lesions and focus a differential diagnosis. The spinal nerve roots consist of dorsal and ventral roots that extend from the spinal cord. The dorsal root ganglion contains a bipolar neuron that is the sensory nerve cell body.

Measurement of strains experienced by viscerofugal nerve cell bodies during mechanosensitive firing using digital image correlation

Mechanosensory neurons detect physical events in the local environments of the tissues that they innervate. Studies of mechanosensitivity of neurons or nerve endings in the gut have related their firing to strain, wall tension, or pressure. Digital image correlation (DIC) is a technique from materials engineering that can be adapted to measure the local physical environments of afferent neurons at high resolution. Flat-sheet preparations of guinea pig distal colon were set up with arrays of tissue markers in vitro. Firing of single viscerofugal neurons was identified in extracellular colonic nerve recordings. The locations of viscerofugal nerve cell bodies were inferred by mapping firing responses to focal application of the nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide. Mechanosensory firing was recorded during load-evoked uniaxial or biaxial distensions. Distension caused movement of surface markers which was captured by video imaging. DIC tracked the markers, interpolating the mechanical state of the gut at the location of the viscerofugal nerve cell body. This technique revealed heterogeneous load-evoked strain within preparations. Local strains at viscerofugal nerve cell bodies were usually smaller than global strain measurements and correlated more closely with mechanosensitive firing. Both circumferential and longitudinal strain activated viscerofugal neurons. Simultaneous loading in circumferential and longitudinal axes caused the highest levels of viscerofugal neuron firing. Multiaxial strains, reflecting tissue shearing and changing area, linearly correlated with mechanosensory firing of viscerofugal neurons. Viscerofugal neurons were mechanically sensitive to both local circumferential and local longitudinal gut strain, and appear to lack directionality in their stretch sensitivity.

The structure of the perineuronal sheath of satellite glial cells (SGCs) in sensory ganglia

In sensory ganglia each nerve cell body is usually enveloped by a satellite glial cell (SGC) sheath, sharply separated from sheaths encircling adjacent neurons by connective tissue. However, following axon injury SGCs may form bridges connecting previously separate perineuronal sheaths. Each sheath consists of one or several layers of cells that overlap in a more or less complex fashion; sometimes SGCs form a perineuronal myelin sheath. SGCs are flattened mononucleate cells containing the usual cell organelles. Several ion channels, receptors and adhesion molecules have been identified in these cells. SGCs of the same sheath are usually linked by adherent and gap junctions, and are functionally coupled. Following axon injury, both the number of gap junctions and the coupling of SGCs increase markedly. The apposed plasma membranes of adjacent cells are separated by 15–20 nm gaps, which form a potential pathway, usually long and tortuous, between connective tissue and neuronal surface. The boundary between neuron and SGC sheath is usually complicated, mainly by many projections arising from the neuron. The outer surface of the SGC sheath is covered by a basal lamina. The number of SGCs enveloping a nerve cell body is proportional to the cell body volume; the volume of the SGC sheath is proportional to the volume and surface area of the nerve cell body. In old animals, both the number of SGCs and the mean volume of the SGC sheaths are significantly lower than in young adults. Furthermore, extensive portions of the neuronal surface are not covered by SGCs, exposing neurons of aged animals to damage by harmful substances.

RESPONSES OF THE NERVE CELL BODY TO AXOTOMY

OBJECTIVE Peripheral nerve injury causes retrograde changes in the damaged neurons, which are beneficial to axonal regeneration. Better understanding of the mechanisms of induction and mediation of these conditioning responses would help to design strategies to invoke stronger regenerative responses in neurons in situations when these responses are inadequate. METHODS Relevant literature is reviewed. RESULTS Experimental preparations that measure the influence of peripheral axotomy on regeneration in the central axons of primary sensory neurons are useful to examine mechanisms of conditioning neurons. Despite 4 decades of speculation, the nature of the damage signals from injured nerves that initiate axonal signals to the nerve cell body remains elusive. Members of the family of neuropoietic cytokines are clearly implicated, but what induces them is unknown. Multiple changes in gene regulation in axotomized neurons have been described, and dozens of growth-associated genes have been identified: neurotrophic factors, transcription factors, molecules participating in axonal transport, and molecules active in the growth cone. The mechanisms of interaction of a few regeneration-associated molecules with the signaling cascades that lead to actin and tubulin remodeling at the growth cone are understood in some detail. In animals, viral gene therapy to deliver regeneration-associated genes to neurons or other local measures to induce these genes can improve regeneration. A few pharmacological agents, administered systemically, have small beneficial effects on axonal regeneration. CONCLUSION Advances in laboratory research have provided knowledge of cell body responses to axotomy with clinical relevance.

GRADUAL NERVE ELONGATION AFFECTS NERVE CELL BODIES AND NEURO-MUSCULAR JUNCTIONS

The purpose of this study is to clarify the reactions of the neuro-muscular junction and nerve cell body to gradual nerve elongation. The sciatic nerves of Japanese white rabbits were lengthened by 30 mm in increments of 0.8 mm/day, 2.0 mm/day and 4.0 mm/day. A scanning electron microscopic examination showed no degenerative change at the neuro-muscular junction, even eight weeks after elongation in the 4-mm group. Hence, neuro-muscular junction is not critical for predicting damage from gradual nerve elongation. There were no axon reaction cells in the 0.8-mm group, a small amount in the 2-mm group, and a large amount in the 4-mm group. The rate of growth associated protein-43 positive nerve cells was significant in the 4-mm group. Hence, the safe speed for nerve cells appeared to be 0.8-mm/day, critical speed to be 2.0-mm/day, and dangerous speed to be 4.0-mm/day in this elongation model.

Looking at Slow Axonal Transport

Neurons are about as polarized as cells ever get. Their axonal process can extend a distance that is up to a million times the diameter of the nerve cell body. Axons have none of the ribosomal machinery responsible for protein synthesis, so all neuronal proteins and peptides must be manufactured near the nucleus and carried out to the periphery. This distribution involves at least two distinct mechanisms, fast axonal transport, moving at almost 500 mm per day, and slow axonal transport, moving only 0.1 to 3 mm per day. It turns out that proteins of the neuronal cytoskeleton, along with many soluble cytosolic proteins, are transported exclusively by the slower process.

Neurotropism, Frozen Muscle Grafts and Other Conduits

Axonal regeneration following nerve transection requires a number of cellular and biochemical phenomena in the axons as well as the nerve cell bodies. The nerve cells must survive the trauma. Since axonal severance means amputation of a large axoplasmic volume from the remaining parts of the nerve cell, the cell body must prepare for increased synthesis of axoplasm to replace the missing parts. A sprouting process must be initiated at the level of transection. Regenerating axonal processes are to regenerate towards peripheral targets, a process regulated by an interaction between genetic mechanisms in the nerve cell body and biochemical information at the molecular level along the pathway.