Hallmarks of peripheral nerve injury and regeneration

Krishnan, Anand; Verge, Valerie M.K.; Zochodne, Douglas W.

doi:10.1016/b978-0-323-90108-6.00014-4

Cited by 2 publications

(2 citation statements)

References 125 publications

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“…Understanding the immediate molecular mechanisms that govern nerve injury response and regeneration is crucial for developing effective therapeutic surgical and pharmacological interventions. Data on up- and down-regulated proteins from experimental studies must also be confirmed in human studies ( Krishnan et al, 2024 ). Following a nerve transection, the proximal nerve end around the site of the lesion and the entire distal nerve end undergoes distinct and extensive biological processes.…”

Section: Introductionmentioning

confidence: 99%

“…Although individual proteins and pathways involved in nerve regeneration have been investigated in mice and rats ( Dahlin, 2023 ; Krishnan et al, 2024 ), there is a lack of comprehensive proteomic analysis comparing the protein profiles of proximal and distal nerve ends post-injury in humans, where the proximal nerve end is considered to exhibit molecular alterations. This gap of knowledge limits our understanding of the molecular environment and sophisticated regulatory mechanisms, particularly in the distal nerve end, which are essential for devising targeted therapeutic strategies and for interpreting findings from experimental studies.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative mass spectrometry analysis of the injured proximal and distal human digital nerve ends

Frostadottir,

Welinder,

Perez

et al. 2024

Front. Mol. Neurosci.

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IntroductionProteomic analysis of injured human peripheral nerves, particularly focusing on events occurring in the proximal and distal nerve ends, remains relatively underexplored. This study aimed to investigate the molecular patterns underlying a digital nerve injury, focusing on differences in protein expression between the proximal and distal nerve ends.MethodsA total of 26 human injured digital nerve samples (24 men; 2 women; median age 47 [30–66] years), harvested during primary nerve repair within 48 h post-injury from proximal and distal nerve ends, were analyzed using mass spectrometry.ResultsA total of 3,914 proteins were identified, with 127 proteins showing significant differences in abundance between the proximal and the distal nerve ends. The downregulation of proteins in the distal nerve end was associated with synaptic transmission, autophagy, neurotransmitter regulation, cell adhesion and migration. Conversely, proteins upregulated in the distal nerve end were implicated in cellular stress response, neuromuscular junction stability and muscle contraction, neuronal excitability and neurotransmitter release, synaptic vesicle recycling and axon guidance and angiogenesis.DiscussionInvestigation of proteins, with functional annotations analysis, in proximal and the distal ends of human injured digital nerves, revealed dynamic cellular responses aimed at promoting tissue degeneration and restoration, while suppressing non-essential processes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantitative mass spectrometry analysis of the injured proximal and distal human digital nerve ends

Frostadottir,

Welinder,

Perez

et al. 2024

Front. Mol. Neurosci.

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Peripheral nerve traction injury modeling in an experiment

Vorodi,

Petriv,

Nekhlopochyn

et al. 2024

INJ

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Background. Peripheral nerve (PN) injuries can lead to significant functional impairment and reduced quality of life. Functional recovery of PN is a complex process dependent on many factors, some of which can be controlled to improve outcomes. The number of wounded people with damage to the peripheral nerves of the limbs can be up to 25 % in war conditions. The degree of disability of patients is 65–70 %, so the issue of restoring peripheral nerves is extremely relevant, especially during wartime. The purpose was to develop a model of PN traction injury in an experiment resulting from longitudinal stretching of the sciatic nerve using a tool modified based on a standard self-retaining retractor, which provides the possibility of reproducing traumatic conditions that most accurately imitate real clinical cases. Materials and methods. The study was conducted on 20 outbreed male rats (average weight of 225 ± 55 g) kept in standard conditions of the vivarium of the State Institution “Romodanov Neurosurgery Institute of the National Academy of Medical Sciences of Ukraine” in compliance with current norms of bioethics. The animals were divided into two groups: the first one (n = 10) — traction injury of the nerve, withdrawal from the experiment after 15 days with further examination of the damaged area with the light and electron microscopy. The second group of animals (n = 10) — traction injury of the nerve, withdrawal from the experiment after 30 days with further examination of the damaged part of the nerve with the help of light and electron microscopy. Before surgery, on the 15th and 30th day after simulating injury (before the nerve harvesting for morphological analysis), the sciatic functional index (SFI) was determined using the walking track test in groups I and II of animals, respectively. Rats were maintained on a standard 12-h light/dark cycle with free access to food and water. The experiment ended by removing the animals from the experiment by injecting a lethal dose of thiopental sodium. For a more detailed analysis, on the 15th and 30th day after the start of the experiment, repeated surgical interventions were performed to collect the appropriate sections of the nerve for morphological examination. For accurate identification of the proximal end of the nerve, the method of applying a ligature to the epineurium was used, which allowed to clearly demarcate the studied areas for further analysis. Structural changes in the nerve tissue were analyzed using light and electron microscopy, which provided high detail of morphological characteristics. Results. At the beginning of the experiment, before traction injury, the SFI in the first group was 2.26 ± 0.27, and in the second group — 3.14 ± 0.53. Fifteen days after injury simulation, the SFI in the first group was 68.90 ± ± 1.61, and in the second group — 70.31 ± 1.75, the difference between the indicators was statistically insignificant (p ≥ 0.05). When comparing the SFI before and after injury, the difference was statistically significant (p < 0.0014 and p < 0.0032, respectively). Thirty days after injury simulation, the SFI in the second group was 32.27 ± 1.13 and, compared to the indicator on the 15th day after the injury, it differed statistically significantly in favor of the indicator after 30 days (p < 0.0026). From the biomechanical point of view, three main types of injuries can be distinguished, when traction is the main traumatic mechanism: elastic stretching, inelastic (plastic) stretching and rupture. Elastic stretching is characterized by the return of the nerve to its original length after removal of traction. With a further increase in the stretching force, the nerve enters the phase of plastic deformation, during which irreversible changes in its structure occur, such as the rupture of axons, endoneural and perineural sheaths. When a certain threshold of stretching is exceeded (in particular, when the hook was moved along racks at position of 9, 10, 11 teeth), nerve rupture occurred. The results of morphological studies are planned to be described in detail in future scientific publications. Conclusions. 1. The model of the peripheral nerve traction injury is objective as evidenced by the sciatic nerve functional index. This technique is easily reproducible and does not require expensive and complex equipment. 2. The use of a model of peripheral nerve traction injury in an experiment, with the aim of studying the therapeutic effects in this type of trauma, will allow to expand the understanding of its patho- and morphogenesis and to improve treatment strategy. 3. Extrapolation of this model to clinical practice will allow to improve the treatment of victims with the consequences of combat injuries to peripheral nerves, where a similar mechanism of trauma often occurs.

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Hallmarks of peripheral nerve injury and regeneration

Cited by 2 publications

References 125 publications

Quantitative mass spectrometry analysis of the injured proximal and distal human digital nerve ends

Quantitative mass spectrometry analysis of the injured proximal and distal human digital nerve ends

Peripheral nerve traction injury modeling in an experiment

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