Journal of Neuroinfectious Diseases
Open Access

Nerve injury; Axon; Diagnostic testing

Introduction to Nerve Injury

The study of peripheral nerve injury began during the American Civil War and has grown significantly since then thanks to developments like the use of molecules that encourage growth [1]. Clinical examination is frequently combined with electro diagnostic tests to determine the location and severity of a peripheral nerve injury. Injuries to the myelin are typically the least severe (neuropraxia), whereas injuries to the axons and supporting structures are typically the most severe (axonotmesis is a moderate injury, while neurotmesis is a severe injury)[2]. Common neurological impairments, such as motor and sensory impairments that are distal to the lesion Neurapraxia is the type of nerve injury with complete recovery that is least severe. The axon remains intact in this instance, but there is myelin damage that prevents the impulse from traveling down the nerve fiber. This typically results in nerve compression or disruptions to the blood supply (ischemia). Within hours to months (on average, 6 to 8 weeks), there is a temporary loss of function that can be reversed [3]. Recovery does not consist of actual regeneration because Wallerian degeneration does not occur. When autonomic function is retained, the involvement of motor function is frequently greater than that of sensory function. Normal compound motor action potential amplitude distal to the lesion on day 10 of electro diagnostic testing with nerve conduction studies suggests mild neurapraxia rather than axonotmesis or neurotmesis as the diagnosis.

This is a more severe nerve injury that results in the loss of the epineurium but preserves the neuronal axon. This kind of nerve damage is typically seen in crush injuries and can result in motor, sensory, and autonomic paralysis. If the force that caused the nerve damage is removed promptly, the axon may regenerate, allowing recovery [4]. The nerve undergoes rapid and complete electrical degeneration, resulting in the loss of voluntary motor units. Axonotmesis involves the interruption of the axon and it’s covering of myelin, but with preservation of the connective tissue framework of the nerve (the encapsulating tissue, the epineurium, and peri neurium). Wallerian degeneration occurs when axonal continuity is lost [5]. Motor end plates will regenerate as long as the endo neural tubules are intact. Muscles distal to the injury site exhibit fibrillations and denervation potentials on electromyography (EMG) 2 to 4 weeks later. With axonotmesis, the loss of both the motor and sensory spines is more extensive than with neurapraxia, and recovery is only possible through the time-consuming regeneration of the axons [6].

Axonotmesis can occur when the nerve is stretched (without causing damage to the epineurium), but it is typically the result of a crush or contusion that is more severe than neurapraxia. The regeneration fibers must cross the injury site, and it may take several weeks for regeneration to occur through the proximal or retrograde area of degeneration [7]. There is typically some retrograde proximal degeneration in the axon before regeneration can occur. The neuritis tip then moves down the distal site, like the hand or wrist. The distal lesion can expand as slowly as 1.5 mm per day while the proximal lesion can expand as rapidly as 2 to 3 mm per day. Regeneration takes weeks to years to complete. Neurotmesis is the most severe injury with no chance of full recovery. It can result from a severe stretch, laceration, or contusion. Both the encapsulating connective tissue and the axon lose continuity [8]. Transection is the most severe form of neurotmesis, but most injuries do not result in a complete loss of nerve continuity but rather internal disruption of nerve structures that affect axons and their covering as well as the epineurium and endometrium[9]. Changes in denervation that are recorded by EMG are identical to those that occur during axonometric injury. A neuroma forms in the proximal stump if the nerve has been completely divided, and there is a complete loss of motor, sensory, and autonomic function [10]. The Sunderland System, a brand-new, more comprehensive classification, is preferable for neurotmesis.

Schwann cells are glial cells in the peripheral nervous system that support neurons by forming myelin that encases nerves. Wallerian degeneration is a process that takes place prior to nerve regeneration and can be described as a cleaning or clearing process that basically prepares the distal stump for innervation [11]. Calcium plays a role in the degeneration of the damaged axon during Wallerian degeneration, when Schwann cells and macrophages collaborate to remove debris from the distal injury site, particularly myelin and the damaged axon. Endometrial tubes are formed by proliferating innervated Schwann cells and the remaining connective tissue basement membrane, resulting in bands of Büngner[12]. A process known as chromatolysis occurs at the neuronal cell body, in which the nucleus migrates to the periphery of the cell body and the endoplasmic reticulum breaks up and disperses. Bands of Büngner are crucial for guiding the regrowing axon. The metabolic function of the cell shifts from producing molecules for synaptic transmission to growth and repair in response to nerve damage. Actin, tubulin, and GAP-43 are some of these factors. When the cell is prepared for axon regeneration, chromatolysis is reversed. Axon regeneration is characterized by the formation of a growth cone that is capable of producing a protease that digests any material or debris that remains in its path of regeneration toward the distal site. Laminin and fibronectin, two molecules made by Schwann cells, are recognized by the growth cone. In Wallerian degeneration, Schwann cells are involved. Not only do they play a role in the phagocytosis of myelin, but they also help recruit macrophages to continue the process. The expression of molecules that are typically unique to inflammatory macrophages has been used to investigate the phagocytic function of Schwann cells. One such molecule, MAC-2, a galactose-specific lectin, is expressed in both Schwann cell-rich and macrophage-deficient degenerating nerves, as well as in macrophage-rich degenerating nerves. Myelin phagocytosis is also linked to the effects of MAC-2 on degenerated nerves. Myelin phagocytosis was found to be positively correlated with the level of MAC-2 expression. Schwann cells are active in demyelination of injured nerves before macrophages are even present at the site of nerve injury, so a lack of MAC-2 expression can even inhibit myelin removal from injury sites. Myelin fragments and lipid droplets are found in the cytoplasm of Schwann cells before macrophages arrive at the injury site, indicating phagocytic activity before macrophages arrive. Schwann cell activity includes recruiting macrophages to the injury site, as shown by electron microscopy and immune histo chemical staining of teased nerve fibers. MCP-1, a monocyte chemo attractant protein, is involved in the recruitment of monocytes and macrophages. MCP-1 mRNA expression and macrophage recruitment increased in tellurium-induced demyelination without axon degeneration, nerve crush with axon degeneration, and nerve transection with axon degeneration, respectively. Additionally, the expression of MCP- 1 mRNA at various levels had an impact. A positive correlation was found between an increase in macrophage recruitment and an increase in MCP-1 mRNA levels. In addition, Schwann cells were found to be the cellular source of MCP-1 by in situ hybridization. Schwann cells are important because they produce neuro trophic factors like nerve growth factor (NGF) and ciliary neuro trophic factor (CNTF), which help the supporting Schwann cells and the damaged nerve grow, as well as neurite promoting factors, which help the axon grow.

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