Can Early Electrical Stimulation Accelerates the Neural Regeneration by Increasing the Expression of BDNF and GDNF in Distal Part of Injured Peripheral Nerve? An Animal Experimental Study

BACKGROUND: The role of neurotrophic factors (brain-derived neurotrophic factors and glial cell line-derived neurotrophic factors) and early electrical stimulation (EES) in the injured nerve has found promising in several studies. However, there is still limited knowledge about the effect of EES in the distal part of the nerve to sustain this level of expression of growth factors. AIM: We aim to evaluate the effects of EES in in neural regeneration by measuring the expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in animal model. METHODS: The research was conducted starting from April to May 2021 using male Wistar rats. Using general anesthesia, the sciatic nerve was cut. The intervention group was treated with EES in the distal stump, right after nerve resection (20 Hz, 1–2 mA, 2–5 s), while the control group received no treatment after nerve resection. A reoperation on day 3 was performed in both groups to measure BDNF and GDNF expression level of the distal nerve tissue by ELISA as well as histopathological examination of sprouting axons of the injured proximal nerve. RESULTS: A total of 32 samples were included in the study. A statistically significant levels of GDNF is found higher in the EES group (n = 16) than the control group (n = 16) (35. 71 pg/100 mg, confidence interval (CI) 95% 23.93, 47.48, p < 0.05). The number of sprouting axons is found lower in the EES group (p < 0.05). The BDNF level is similar between the two groups, however not significant. After a subgroup analysis, it was found that the greater the level of GDNF, the fewer the axon sprouts in both groups (fewer axon group 58.35 [n = 22, CI 95% 45.14, 71.55] vs. more axon group 47.14 [n = 10, CI 95% 35.33, 58.95]), p < 0.05. CONCLUSION: The EES proves its benefit in accelerating the axonal regeneration by increasing the expression GDNF in the distal nerve stumps in the electrical excited degenerated sciatic nerve in the rat model.

Meta-Analysis Reveals Transcription Factor Upregulation in Cells of Injured Mouse Sciatic Nerve

Following peripheral nerve injury, transcription factors upregulated in the distal nerve play essential roles in Schwann cell reprogramming, fibroblast activation and immune cell function to create a permissive distal nerve environment for axonal regrowth. In this report, we first analysed four microarray data sets to identify transcription factors that have at least twofold upregulation in the mouse distal nerve stump at day 3 and day 7 post-injury. Next, we compared their relative mRNA levels through the analysis of an available bulk mRNA sequencing data set at day 5 post-injury. We then investigated the expression of identified TFs in analysed single-cell RNA sequencing data sets for the distal nerve at day 3 and day 9 post-injury. These analyses identified 55 transcription factors that have at least twofold upregulation in the distal nerve following mouse sciatic nerve injury. Expression profile for the identified 55 transcription factors in cells of the distal nerve stump was further analysed on the scRNA-seq data. Transcription factor network and functional analysis were performed in Schwann cells. We also validated the expression pattern of Jun, Junb, Runx1, Runx2, and Sox2 in the mouse distal nerve stump by immunostaining. The findings from our study not only could be used to understand the function of key transcription factors in peripheral nerve regeneration but also could be used to facilitate experimental design for future studies to investigate the function of individual TFs in peripheral nerve regeneration.

Cubital tunnel syndrome

Cubital tunnel syndrome (CuTS) is the second most common compression neuropathy of the upper limb, presenting with disturbance of ulnar nerve sensory and motor function. The ulnar nerve may be dynamically compressed during movement, statically compressed due to reduction in tunnel volume or compliance, and tension forces may cause ischaemia or render the nerve susceptible to subluxation, further causing local swelling, compression inflammation and fibrosis. Superiority of one surgical technique for the management of CuTS has not been demonstrated. Different techniques are selected for different clinical situations with simple decompression being the most common procedure due to its efficacy and low complication rate. Adjunctive distal nerve transfer for denervated muscles using an expendable motor nerve to restore the axon population in the distal nerve is in its infancy but may provide a solution for severe intrinsic weakness or paralysis. Cite this article: EFORT Open Rev 2021;6:743-750. DOI: 10.1302/2058-5241.6.200129

Trends in Brachial Plexus Surgery: Characterizing Contemporary Practices for Exploration of Supraclavicular Plexus

Background There is variability in treatment strategies for patients with brachial plexus injury (BPI). We used qualitative research methods to better understand surgeons’ rationale for treatment approaches. We hypothesized that distal nerve transfers would be preferred over exploration and nerve grafting of the brachial plexus. Methods We conducted semi-structured interviews with BPI surgeons to discuss 3 case vignettes: pan-plexus injury, upper trunk injury, and lower trunk injury. The interview guide included questions regarding overall treatment strategy, indications and utility of brachial plexus exploration, and the role of nerve grafting and/or nerve transfers. Interview transcripts were coded by 2 researchers. We performed inductive thematic analysis to collate these codes into themes, focusing on the role of brachial plexus exploration in the treatment of BPI. Results Most surgeons routinely explore the supraclavicular brachial plexus in situations of pan-plexus and upper trunk injuries. Reasons to explore included the importance of obtaining a definitive root level diagnosis, perceived availability of donor nerve roots, timing of anticipated recovery, plans for distal reconstruction, and the potential for neurolysis. Very few explore lower trunk injuries, citing concern with technical difficulty and unfavorable risk-benefit profile. Conclusions Our analysis suggests that supraclavicular exploration remains a foundational component of surgical management of BPI, despite increasing utilization of distal nerve transfers. Availability of abundant donor axons and establishing an accurate diagnosis were cited as primary reasons in support of exploration. This analysis of surgeon interviews characterizes contemporary practices regarding the role of brachial plexus exploration in the treatment of BPI.

About vasodilating fibers of the sciatic nerve. Preliminary announcement

The paths along which the vasodilator fibers, after leaving the spinal cord, follow to the distal nerve, have repeatedly attracted the attention of physiologists.

Purposeful Misalignment of Severed Nerve Stumps in a Standardized Transection Model Reveals Persistent Functional Deficit With Aberrant Neurofilament Distribution

ABSTRACT Background Functional recovery following primary nerve repair of a transected nerve is often poor even with advanced microsurgical techniques. Recently, we developed a novel sciatic nerve transection method where end-to-end apposition of the nerve endings with minimal gap was performed with fibrin glue. We demonstrated that transected nerve repair with gluing results in optimal functional recovery with improved axonal neurofilament distribution profile compared to the end-to-end micro-suture repair. However, the impact of axonal misdirection and misalignment of nerve fascicles remains largely unknown in nerve-injury recovery. We addressed this issue using a novel nerve repair model with gluing. Methods In our complete “Flip and Transection with Glue” model, the nerve was “first” transected to 40% of its width from each side and distal stump was transversely flipped, then 20 µL of fibrin glue was applied around the transection site and the central 20% nerve was completely transected before fibrin glue clotting. Mice were followed for 28 days with weekly assessment of sciatic function. Immunohistochemistry analysis of both sciatic nerves was performed for neurofilament distribution and angiogenesis. Tibialis anterior muscles were analyzed for atrophy and histomorphometry. Results Functional recovery following misaligned repair remained persistently low throughout the postsurgical period. Immunohistochemistry of nerve sections revealed significantly increased aberrant axonal neurofilaments in injured and distal nerve segments compared to proximal segments. Increased aberrant neurofilament profiles in the injured and distal nerve segments were associated with significantly increased nerve blood-vessel density and branching index than in the proximal segment. Injured limbs had significant muscle atrophy, and muscle fiber distribution showed significantly increased numbers of smaller muscle fibers and decreased numbers of larger muscle fibers. Conclusions These findings in a novel nerve transection mouse model with misaligned repair suggest that aberrant neurofilament distributions and axonal misdirections play an important role in functional recovery and muscle atrophy.