Nerve Transection Research Articles

Left cardiac vagotomy rapidly reduces contralateral cardiac vagal electrical activity in anesthetized Göttingen minipigs

BackgroundThe impact of acute unilateral injury on spontaneous electrical activity in both vagus nerves at the heart level is poorly understood. We investigated the immediate neuroelectrical response after right or left cardiac vagal nerve transection (VNTx) by recording spiking activity of each heart vagus nerve (VN). MethodsFourteen male Göttingen minipigs underwent sternotomy. Multi-electrode cuffs were implanted below the cut level to record vagal electroneurographic signals during electrocardiographic and hemodynamic monitoring, before and immediately after cardiac VNTx (left: L-cut, n = 6; right: R-cut, n = 8). ResultsLeft cardiac VNTx significantly reduced multi-unit electrical activity (MUA) firing rate in the vagal stump (−30.7% vs pre-cut) and intact right VN (−21.8% vs pre-cut) at the heart level, without affecting heart rate, heart rate variability, or hemodynamics. In contrast, right cardiac VNTx did not acutely alter MUA in either VN but slightly increased (p < 0.022) the root mean square of successive RR interval differences (rMSSD), an index of parasympathetic outflow, without affecting hemodynamics. ConclusionsOur study reveals an early left-lateralized pattern in vagal spiking activity following unilateral cardiac vagotomy. These findings enhance understanding of the neuroelectrical response to vagal injury and provide insights into preserving vagal outflow after unilateral cardiac vagotomy. Importantly, monitoring spiking activity of the cardiac right VN may predict onset of left vagal pathway injury, which is detrimental to cardiac patients and can occur as a complication of catheter ablation for atrial fibrillation.

Ropivacaine promotes axon regeneration by regulating Nav1.8-mediated macrophage signaling after sciatic nerve injury in rats.

Continuous nerve block with ropivacaine is commonly performed after repair surgery for traumatic peripheral nerve injuries. After peripheral nerve injury, tetrodotoxin-resistant voltage-gated sodium channel Nav1.8 is upregulated and contributes to macrophage inflammation. We investigated whether ropivacaine promotes peripheral nerve regeneration through Nav1.8-mediated macrophage signaling. A sciatic nerve transection-repair (SNT) model was established in adult Sprague-Dawley rats of both sexes. The rats received 0.2% ropivacaine or 10 μM Nav1.8-selective inhibitor A-803467 around the injured site or near the sacrum for 3 days. Nerve regeneration was evaluated using behavioral, electrophysiological, and morphological examinations. Moreover, myelin debris removal, macrophage phenotype, Nav1.8 expression, and neuropeptide expression were assessed using immunostaining, enzyme-linked immunosorbent assay, and western blotting. Compared to the SNT-plus-vehicle group, the sensory, motor, and sensory-motor coordination functions of the two ropivacaine groups were significantly improved. Electrophysiological (mean ± SD: recovery index of amplitude, vehicle 0.43 ± 0.17 vs. ropivacaine 0.83 ± 0.25, n = 11, P ˂ 0.001) and histological analysis collectively indicated that ropivacaine significantly promoted axonal regrowth (percentage of NF-200 positive area: vehicle 19.88 ± 2.81 vs. ropivacaine 31.07 ± 2.62, n = 6, P ˂ 0.001). We also found that, compared to the SNT-plus-vehicle group, the SNT-plus-ropivacaine group showed faster clearance of myelin debris, accompanied by significantly increased macrophage infiltration and transition from the M1 to M2 phenotype. Moreover, ropivacaine significantly attenuated Nav1.8 upregulation at 9-days after sciatic nerve transection (vehicle 4.12 ± 0.30-fold vs. ropivacaine 2.75 ± 0.36-fold, n = 5, P ˂ 0.001), which coincided with the increased expression of chemokine ligand 2 and substance P. Similar changes were observed when using the selective Nav1.8 channel inhibitor A-803467. Continuous nerve block with ropivacaine promotes the structural and functional recovery of injured sciatic nerves, possibly by regulating Nav1.8-mediated macrophage signaling.

MuRF-1 is Involved in Laryngeal Muscle Denervation Atrophy by Regulating G-Actin Ubiquitination.

Muscle RING-finger protein-1 (MuRF-1), an E3 ubiquitin ligase, has been reported to aggravate skeletal muscle denervated atrophy by mediating the ubiquitination degradation of multiple proteins, whereas the molecular mechanism underlying MuRF-1-mediated internal laryngeal muscle denervated atrophy remains unknown. A rat unilateral recurrent laryngeal nerve (RLN) transection model was established to evaluate denervated muscle atrophy of the larynx. The expression of MuRF-1, G- and F-actin in thyroarytenoid muscle (TA) myocytes before and after RLN injury was analyzed by immunofluorescence and Western blotting. Coimmunoprecipitation experiments detected molecular interactions between MuRF-1 and G-actin. Immunoprecipitation tested MuRF-1-mediated ubiquitination of G-actin in denervated and innervated TA muscle tissues. The shRNA-MuRF-1 AAV was used to suppress MuRF-1 expression in denervated TA muscles in vivo. First, MuRF-1 expression was significantly elevated in denervated TA muscle compared to innervated TA muscle (p < 0.001). Second, there was a progressive increase in the G/F-actin ratio in TA myocytes from day 3 to 14 after RLNI (p < 0.01). Furthermore, colocalization of MuRF-1 and G-actin in denervated TA myocytes was observed. Moreover, the upregulation of MuRF-1 was closely associated with the ubiquitination of G-actin in denervated TA myocytes and muscle tissues. Knockdown of MuRF-1 decelerated the degree of TA muscle atrophy compared with that in the Blank and NC groups (p < 0.001) but seemed to promote the compensatory movement of the healthy side. Collectively, we illustrate a novel molecular mechanism underlying MuRF-1-mediated internal laryngeal muscle denervated atrophy in that MuRF-1 could promote disequilibrium of the G/F-actin ratio by regulating G-actin ubiquitination. NA Laryngoscope, 134:855-864, 2024.

The Use of Nerve Caps after Nerve Transection in Headache Surgery: Cadaver and Case Reports.

Nerve transection with nerve reconstruction is part of the treatment algorithm for patients with refractory pain after greater occipital nerve (GON) and lesser occipital nerve (LON) decompression or during primary decompression when severe nerve injury or neuroma formation is present. Importantly, the residual nerve stump is often best addressed via contemporary nerve reconstruction techniques to avoid recurrent pain. As a primary aim of this study, nerve capping is explored as a potential viable alternative that can be utilized in certain headache cases to mitigate pain. The technical feasibility of nerve capping after GON/LON transection was evaluated in cadaver dissections and intraoperatively. Patient-reported outcomes in the 3- to 4-month period were compiled from clinic visits. At 1-year follow-up, subjective outcomes and Migraine Headache Index scores were tabulated. Two patients underwent nerve capping as a treatment for headaches refractory to medical therapy and surgical decompressions with significant improvement to total resolution of pain without postoperative complications. These improvements on pain frequency, intensity, and duration remained stable at a 1-year time point (Migraine Headache Index score reductions of -180 to -205). Surgeons should be equipped to address the proximal nerve stump to prevent neuroma and neuropathic pain recurrence. Next to known contemporary nerve reconstruction techniques such as targeted muscle reinnervation/regenerative peripheral nerve interface and relocation nerve grafting, nerve capping is another viable method for surgeons to address the proximal nerve stump in settings of GON and LON pain. This option exhibits short operative time, requires only limited dissection, and yields significant clinical improvement in pain symptoms.

Two Cases of Left Hip Heterotopic Ossification Treated with Surgery and their Outcomes Postoperatively

52-year-old woman was admitted to Trauma and Orthopedics department (TOD) due to septic arthritis (SA) in left hip joint (LHJ). Patient underwent three consecutive open debridement procedures. During the treatment, an intracerebral hematoma was discovered. Upon rehabilitation patient indicated severe pain in LHJ that impaired movement. Three months after admission CT showed heterotopic ossification (HO) in LHJ. Patient was recommended to complete treating postinfectious complications and refer to TOD for further evaluation and discussing treatment options. Five months after the first presentation, complete mechanical block could be seen in LHJ due to HO. Open left hip ossificate resection and LHJ redressation were performed. During procedure significant increase in range of motion (ROM) was obtained. Iatrogenic transection of the femoral nerve occurred and was treated surgically. After surgery, patient was subjected to early rehabilitation and later forwarded to rehabilitation department. Increase of active and passive ROM remained. 34-year-old man was admitted to TOD due to polytrauma, including multiple hip and acetabular fractures. Patient underwent three surgical interventions due to fractures. Month after admission, postoperative deep tissue infection in the fracture and Covid-19 were discovered and treated. Two years later, patient returned to TOD complaining about significant impairment of ROM in LHJ due to HO, which was surgically removed. Surgical treatment is rarely chosen for treatment of HO since alleviation of pain is not worth the risks, and HO can reoccur, preferring treatment with exercise and indomethacin, but when a significant increase of ROM is expected, surgical treatment is justified. These case reports show how surgical treatment of HO with mixed origin in patients with good expected outcomes and high involvement in their own rehabilitation should be at least considered. It is important to emphasize both pre and postoperative rehabilitation and prophylaxis.

ПАРАМЕТРЫ ПОХОДКИ КРЫС С ПЕРИФЕРИЧЕСКОЙ НЕЙРОПАТИЕЙ ПРИ ТРАНСПЛАНТАЦИИ МЕЗЕНХИМАЛЬНЫХ СТВОЛОВЫХ КЛЕТОК И ФАРМАКОЛОГИЧЕСКОЙ СТИМУЛЯЦИИ КАННАБИНОИДНЫХ РЕЦЕПТОРОВ II ТИПА

Background. The study of the role of cannabinoid CB2 receptors in the effectiveness of adipose-derived (AD) mesenchymal stem cells (MSCs) in preventing motor activity disorders in the affected limb will deepen understanding of the mechanisms of MSCs effects when administered locally. Aim. To evaluate the effect of pharmacological stimulation of cannabinoid CB2 receptors during transplantation of AD MSCs on changes in gait parameters in rats in a model of peripheral neuropathy. Material and methods. In 40 male Wistar rats peripheral neuropathic pain was modeled by sciatic nerve transection. On the 7th day after NP modeling, AD MSCs transplantation was performed without additional interventions upon the pharmacological stimulation of CB2 receptors in the area of sciatic nerve transection, as well as after stimulation of CB2 receptors on the AD MSCs membranes during pretreatment. Within 90 days a detailed analysis of the gait was carried out using the CatWalk XT 10.6. Results. Transplantation of AD MSCs accelerated the recovery of dynamic gait parameters, as well as sciatic functional index, and abolished the development of static gait disturbances in rats after sciatic nerve transection. Significant differences in the analyzed gait parameters in the study groups with AD MSCs transplantation were not found. Conclusion. Pharmacological stimulation of CB2 receptors did not enhance or suppress the effect of AD MSCs on the rate of recovery of gait parameters in experimental animals.

Outcome of lateral retinacular nerve transection combined with release for recalcitrant iliotibial band friction syndrome.

In this retrospective study, a technique consisting in neurolysis of the lateral retinacular nerve combined with a partial release through elliptic excision of the iliotibial band (ITB) is evaluated for efficacy in recalcitrant ITB friction syndrome and compared with results from other techniques reported in literature. From April 2014 to December 2017, 21 patients suffering from recalcitrant ITB friction syndrome were surgically treated with the aforementioned technique. 15 patients (15 knees) were available for a written retrospective reassessment after completion of a follow-up period of at least 12 months. Residual pain was scored using the Visual Analogue Scale (VAS). The functional outcome was evaluated by two patient reported outcome measurement scales (PROMs), the Lysholm and the International Knee Documentation Committee (IKDC) score. Return to sport was analysed by duration of the inactivity period as well as by the Tegner score. Overall satisfaction was evaluated using a modified Boyden scale. At final follow-up of one year, the performed intervention resulted in a pain reduction (VAS 4.2 (1-8) to 1.4 (0-6)) and improved knee function (Lysholm 59.53 to 87.73, IKDC 75) with return to sport (Tegner 4.3 to 5.4) after a median of 23.8 weeks (6 to 52). Twelve patients reported good or excellent results (80%) at final follow-up, and 12 patients (80%) would undergo surgery again, if necessary. The treatment of recalcitrant ITB friction syndrome by combining neurectomy of the lateral retinacular nerve with elliptic excision of the ITB resulted in good to excellent results in 80% of treated cases with return to sport in 93%.

Histological Comparison of Porcine Small Intestine Submucosa and Bovine Type-I Collagen Conduit for Nerve Repair in a Rat Model

After nerve injury, macrophages and Schwann cells remove axon and myelin debris. We hypothesized that nerves repaired with different conduit materials will result in varying levels of these cell populations, which impacts Wallerian degeneration and axonal regeneration. We performed a unilateral sciatic nerve transection in 18 rats. The nerves were repaired with small intestine submucosa (SIS, n= 9) or isolated type-I collagen (CLC, n= 9) conduits. Rats were monitored for 4 weeks. Histology samples were obtained from the proximal nerve, mid-implant, and distal nerve regions. Samples were stained for total macrophages, M2 macrophages, foamy phagocytes, Schwann cells, vascular components, axon components, and collagen density. Distal nerve analyses showed higher populations of total macrophages and M2 macrophages in SIS-repaired nerves and higher density of foamy phagocytes in CLC-repaired nerves. Proximal nerve, mid-implant, and distal nerve analyses showed higher Schwann cell and vascular component densities in SIS-repaired nerves. Axon density was higher in the mid-implant region of SIS-repaired nerves. Collagen staining in the mid-implant was scant, but less collagen density was observed in SIS-repaired versus CLC-repaired nerves. In the distal nerve, the following were observed: (1) lower total macrophages in CLC-repaired nerves, suggesting lower overall inflammation versus SIS-repaired nerves; (2) higher M2 macrophages in SIS-repaired versus CLC-repaired nerves, a driving factor for higher total macrophages and indicative of an inflammation resolution response in SIS-repaired nerves; and (3) a lower foamy phagocyte density in SIS-repaired nerves, suggesting earlier resolution of Wallerian degeneration versus CLC-repaired nerves. In the proximal nerve, mid-implant, and distal nerve, higher Schwann cell and vascular component densities were noted in SIS-repaired nerves. In the mid-implant, a higher axon component density and a lower collagen density of the SIS-repaired nerves versus CLC-repaired nerves were noted. These results indicate more robust nerve regeneration with less collagen deposition. This invivo study evaluated two common conduit materials that are used in peripheral nerve repair. Clinical outcomes of nerves repaired with conduits may be impacted by the response to different conduit materials. These nerve repair responses include Wallerian degeneration, nerve regeneration, and nerve scarring. This study evaluated Wallerian degeneration using total macrophages, M2 macrophages, and foamy phagocytes. Nerve regeneration was evaluated using Schwann cells and axons. Nerve scarring was evaluated using vascular and collagen density.

Active shrinkage protects neurons following axonal transection

Trauma, vascular events, or neurodegenerative processes can lead to axonal injury and eventual transection (axotomy). Neurons can survive axotomy, yet the underlying mechanisms are not fully understood. Excessive water entry into injured neurons poses a particular risk due to swelling and subsequent death. Using invitro and invivo neurotrauma model systems based on laser transection and surgical nerve cut, we demonstrated that axotomy triggers actomyosin contraction coupled with calpain activity. As a consequence, neurons shrink acutely to force water out through aquaporin channels preventing swelling and bursting. Inhibiting shrinkage increased the probability of neuronal cell death by about 3-fold. These studies reveal a previously unrecognized cytoprotective response mechanism to neurotrauma and offer a fresh perspective on pathophysiological processes in the nervous system.

Treatments with the specific δ-secretase inhibitor, compound 11, promote the regeneration of motor and sensory axons after peripheral nerve injury.

Limited axon regeneration following peripheral nerve injury may be related to activation of the lysosomal protease, asparaginyl endopeptidase (AEP, δ-secretase) and its degradation of the microtubule associated protein, Tau. Activity of AEP was increased at the site of sciatic nerve transection and repair but blocked in mice treated systemically with a specific AEP inhibitor, compound 11 (CP11). Treatments with CP11 enhanced axon regeneration in vivo. Amplitudes of compound muscle action potentials recorded 4 weeks after nerve transection and repair and 2 weeks after daily treatments with CP11 were double those of vehicle-treated mice. At that time after injury, axons of significantly more motor and sensory neurons had regenerated successfully and reinnervated the tibialis anterior and gastrocnemius muscles in CP11-treated mice than vehicle-treated controls. In cultured adult dorsal root ganglion neurons derived from wild type mice that were treated in vitro for 24 h with CP11, neurites were nearly 50% longer than in vehicle-treated controls and similar to neurite lengths in cultures treated with the TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF). Combined treatment with CP11 and 7,8-DHF did not enhance outgrowth more than treatments with either one alone. Enhanced neurite outgrowth produced by CP11 was found also in the presence of the TrkB inhibitor, ANA-12, indicating that the enhancement was independent of TrkB signalling. Longer neurites were found after CP11 treatment in both TrkB+ and TrkB- neurons. Delta secretase inhibition by CP11 is a treatment for peripheral nerve injury with great potential.

Effects of Citicoline and Atorvastatin Administration on the Regenerative Capacity of the Distal Segment of the Transected Sciatic Nerve in Conditions of Delayed Nerve Repair

Introduction: The reduced organ function following delayed nerve repair highlights the need for pharmacological interventions. In this regard, many chemical agents have been administered after nerve injury; however, their functional outcomes are not satisfying yet. The present study aimed to evaluate the effects of the administration of citicoline and atorvastatin on the regenerative capacity of the distal end of the transected sciatic nerve throughout a delayed nerve repair period. Method: The sciatic nerve of male rats (250-300 g) was transected, and the animals were intraperitoneally administrated citicoline (200 mg/kg, n=5), atorvastatin (5 mg/kg, n=5), citicoline + atorvastatin, and vehicles (control groups 1 and 2, n=5) for one month. In the sham group (n=5), the sciatic nerve was only exposed. After one month, the transected nerve was repaired. Fourteen weeks after surgical repair, morphometric and electron microscopic evaluations were performed on the nerve. Results: In the present study, improvement in the structural (fiber diameter, axon diameter, and myelin thickness, etc.) and ultrastructural (degree of myelin destruction) indices of the distal segment of the nerve was observed in the citicoline and atorvastatin groups compared to the control groups (P&lt; 0.01). In addition, the nerve structural and ultrastructural indices in the citicoline + atorvastatin group were better than each citicoline and atorvastatin group. Conclusion: The results of this study showed that the administration of citicoline and atorvastatin leads to maintaining the regeneration capacity of the distal part of the nerve in the condition of delayed nerve repair

Mechanisms of Microglia Proliferation in a Rat Model of Facial Nerve Anatomy.

Although microglia exist as a minor glial cell type in the normal state of the brain, they increase in number in response to various disorders and insults. However, it remains unclear whether microglia proliferate in the affected area, and the mechanism of the proliferation has long attracted the attention of researchers. We analyzed microglial mitosis using a facial nerve transection model in which the blood-brain barrier is left unimpaired when the nerves are axotomized. Our results showed that the levels of macrophage colony-stimulating factor (M-CSF), cFms (the receptor for M-CSF), cyclin A/D, and proliferating cell nuclear antigen (PCNA) were increased in microglia in the axotomized facial nucleus (axotFN). In vitro experiments revealed that M-CSF induced cFms, cyclin A/D, and PCNA in microglia, suggesting that microglia proliferate in response to M-CSF in vivo. In addition, M-CSF caused the activation of c-Jun N-terminal kinase (JNK) and p38, and the specific inhibitors of JNK and p38 arrested the microglial mitosis. JNK and p38 were shown to play roles in the induction of cyclins/PCNA and cFms, respectively. cFms was suggested to be induced through a signaling cascade of p38-mitogen- and stress-activated kinase-1 (MSK1)-cAMP-responsive element binding protein (CREB) and/or p38-activating transcription factor 2 (ATF2). Microglia proliferating in the axotFN are anticipated to serve as neuroprotective cells by supplying neurotrophic factors and/or scavenging excite toxins and reactive oxygen radicals.

Chemokine CCL7 mediates trigeminal neuropathic pain via CCR2/CCR3-ERK pathway in the trigeminal ganglion of mice.

Chemokine-mediated neuroinflammation plays an important role in the pathogenesis of neuropathic pain. The chemokine CC motif ligand 7 (CCL7) and its receptor CCR2 have been reported to contribute to neuropathic pain via astrocyte-microglial interaction in the spinal cord. Whether CCL7 in the trigeminal ganglion (TG) involves in trigeminal neuropathic pain and the involved mechanism remain largely unknown. The partial infraorbital nerve transection (pIONT) was used to induce trigeminal neuropathic pain in mice. The expression of Ccl7, Ccr1, Ccr2, and Ccr3 was examined by real-time quantitative polymerase chain reaction. The distribution of CCL7, CCR2, and CCR3 was detected by immunofluorescence double-staining. The activation of extracellular signal-regulated kinase (ERK) was examined by Western blot and immunofluorescence. The effect of CCL7 on neuronal excitability was tested by whole-cell patch clamp recording. The effect of selective antagonists for CCR1, CCR2, and CCR3 on pain hypersensitivity was checked by behavioral testing. Ccl7 was persistently increased in neurons of TG after pIONT, and specific inhibition of CCL7 in the TG effectively relieved pIONT-induced orofacial mechanical allodynia. Intra-TG injection of recombinant CCL7 induced mechanical allodynia and increased the phosphorylation of ERK in the TG. Incubation of CCL7 with TG neurons also dose-dependently enhanced the neuronal excitability. Furthermore, pIONT increased the expression of CCL7 receptors Ccr1, Ccr2, and Ccr3. The intra-TG injection of the specific antagonist of CCR2 or CCR3 but not of CCR1 alleviated pIONT-induced orofacial mechanical allodynia and reduced ERK activation. Immunostaining showed that CCR2 and CCR3 are expressed in TG neurons, and CCL7-induced hyperexcitability of TG neurons was decreased by antagonists of CCR2 or CCR3. CCL7 activates ERK in TG neurons via CCR2 and CCR3 to enhance neuronal excitability, which contributes to the maintenance of trigeminal neuropathic pain. CCL7-CCR2/CCR3-ERK pathway may be potential targets for treating trigeminal neuropathic pain.

Development and Application of Automated Vocal Fold Tracking Software in a Rat Surgical Model.

The rat is a widely used model for studying vocal fold (VF) function after recurrent laryngeal nerve injury, but common techniques for evaluating rat VF motion remain subjective and imprecise. To address this, we developed a software package, called RatVocalTracker1.0 (RVT1.0), to quantify VF motion and tested it on rats with iatrogenic unilateral vocal fold paralysis (VFP). A deep neural network was trained to identify the positions of the VFs andarytenoid cartilages (ACs) in transoral laryngoscope videos of the rat glottis. Software was developed to estimate glottic midline, VF displacement, VF velocity, and AC angle. The software was applied to laryngoscope videos of adult rats before and after right recurrent and superior laryngeal nerve transection (N = 15; 6M, 9F). All software calculated metrics were compared before and after injury and validated against manually calculated metrics. RVT1.0 accurately tracked and quantified VF displacement, VF velocity, and AC angle. Significant differences were found before and after surgery for all RVT1.0 calculated metrics. There was strong agreement between programmatically and manually calculated measures. Automated analysis was also more efficient than nearly all manual methods. This approach provides fast, accurate assessment of VF motion in rats with minimal labor and allows for quantitative comparison of lateral differences in movement. Through this novel analysis method, we can differentiate healthy movement from unilateral VFP. RVT1.0 is open-source and will be a valuable tool for researchers using the rat model for laryngology research. NA Laryngoscope, 134:340-346, 2024.

THE EFFICACY OF CORTICOSTEROID AFTER FACIAL NERVE NEURORRHAPHY: A SYSTEMATIC REVIEW

Background: In case of comple transection of facial nerve, it is unclear whether or not corticosteroids will be beneficial after facial nerve neurorrhaphy.&#x0D; Aim: The purpose of this systematic review was to determine whether or not corticosteroids are effective in promoting facial nerve regeneration and functional recovery following complete transection and neurorrhaphy.&#x0D; Methods: Randomized controlled trials on human and animal models from Ovid MEDLINE and Ovid EMBASE that studied the efficacy of corticosteroids in total facial nerve damage followed by neurorrhaphy. Electrophysiology, histology, and functional recovery were the methods that were used to evaluate the results. On the other hand, there was no randomised controlled experiment carried out on humans. In a clinical context, it's possible that it won't be possible to conduct human trials that involve histology.&#x0D; Results: Six animal investigations with a total of 248 participants met the inclusion criteria. Electrophysiological results revealed no differences between systemic corticosteroids and controls in terms of latency and amplitude. The results of a comparison between topical corticosteroid and the control group revealed no differences in latency and amplitude. In histologic outcomes, there were no differences in axon diameter between the systemic corticosteroid and control groups; however, the control group had thicker myelin. Comparing systemic corticosteroid to a placebo in terms of eye blinking, the results favoured the placebo.&#x0D; Conclusion: When analysing electrophysiologic and functional recovery outcomes in animal models, this study did not demonstrate any possible benefits of systemic or topical corticosteroid administrations after facial nerve neurorrhaphy in complete transection.

The brain functional connectivity alterations in traumatic patients with olfactory disorder after low-level laser therapy demonstrated by fMRI.

Low-level laser therapy (LLLT) has been clinically accepted to accelerate the nerve regeneration process after a nerve injury or transection. We aimed to investigate the neuronal basis and the influence of LLLT on brain functional networks in traumatic patients with olfactory dysfunction. Twenty-four Patients with traumatic anosmia/hyposmia were exposed to pleasant olfactory stimuli during a block-designed fMRI session. After a 10-week period, patients as control group and patients who had completed the sessions of LLLT were invited for follow-up testing using the same fMRI protocol. Two-sample t-tests were conducted to explore group differences in activation responding to odorants (p-FDR-corrected <0.05). Differences of functional connectivity were compared between the two groups and the topological features of the olfactory network were calculated. Correlation analysis was performed between graph parameters and TDI score. Compared to controls, laser-treated patients showed increased activation in the cingulate, rectus gyrus, and some parts of the frontal gyrus. Shorter pathlength (p = 0.047) and increased local efficiency (p = 0.043) within the olfactory network, as well as decreased inter-network connectivity within the whole brain were observed in patients after laser surgery. Moreover, higher clustering and local efficiency were related to higher TDI score, as manifested in increased sensitivity to identify odors. The results support that low-level laser induces neural reorganization process and make new connections in the olfactory structures. Furthermore, the connectivity parameters may serve as potential biomarkers for traumatic anosmia or hyposmia by revealing the underlying neural mechanisms of LLLT.

Metabolomic profiling of a neurodegenerative retina following optic nerve transection.

The degeneration of retinal ganglion cells (RGCs) often causes irreversible vision impairment. Prevention of RGC degeneration can prevent or delay the deterioration of visual function. The present study aimed to investigate retinal metabolic profiles following optic nerve transection (ONT) injury and identify the potential metabolic targets for the prevention of RGC degeneration. Retinal samples were dissected from ONT group and non‑ONT group. The untargeted metabolomics were carried out using liquid chromatography‑tandem mass spectrometry. The involved pathways and biomarkers were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and MetaboAnalyst 5.0. In the ONT group, 689 disparate metabolites were detected, including lipids and lipid‑like molecules. A total of 122 metabolites were successfully annotated and enriched in 50 KEGG pathways. Among them, 'sphingolipid metabolism' and 'primary bile acid biosynthesis' were identified involved in RGC degeneration. A total of five metabolites were selected as the candidate biomarkers for detecting RGC degeneration with an AUC value of 1. The present study revealed that lipid‑related metabolism was involved in the pathogenesis of retinal neurodegeneration. Taurine, taurochenodesoxycholic acid, taurocholic acid (TCA), sphingosine, and galabiosylceramide are shown as the promising biomarkers for the diagnosis of RGC degeneration.

Sensory recovery and the role of innervated flaps in autologous breast reconstruction-a narrative review.

Continuing (micro)surgical developments result in satisfactory aesthetic outcomes after autologous breast reconstruction. However, sensation recovers poorly and remains a source of dissatisfaction and potential harm. Sensory nerve coaptation is a promising technique to improve sensation in the reconstructed breast. In this literature review an overview of current knowledge about sensory recovery in autologous breast reconstruction and the role of innervated flaps is presented. A thorough PubMed search was conducted, using the terms "autologous breast reconstruction", "innervated" and "sensation". The breast skin is predominantly innervated by the second until sixth intercostal nerve. Some nerves can occasionally be spared during mastectomy, especially during nipple-sparing mastectomy, but transection of sensory nerves is inevitable and leads to impaired sensation. Besides unpleasant, this is unanticipated by patients and negatively influences quality of life. Coaptation between the third anterior intercostal nerve and a sensory nerve from the donor site improves sensory recovery. The donor site and nerve vary, depending on the flap type chosen. The sensory nerves from the commonly used abdominal DIEP flap originate from the 7th until 12th thoracic spinal nerves. Non-abdominal flaps, including the back, buttocks, or thigh area, can also be accompanied with a sensory nerve. Nerve coaptation can be performed directly, or by using grafts or conduits to obtain tensionless repair if necessary. It can be utilized in both immediate as well as delayed autologous breast reconstruction. No adverse outcomes of nerve coaptation have been described. And, most importantly: improved sensory recovery improves patient satisfaction and quality of life. Restoring sensation is, besides restoring aesthetic appearance, an important goal in breast reconstruction. Current evidence unambiguously demonstrates superiority of innervated flaps compared to non-innervated flaps. Sensory recovery initiates earlier and it approaches normal sensation more closely in innervated flaps, without associated risks or extensive increase in operating time. This improves patient satisfaction and quality of life. It is, therefore, a valuable addition to autologous breast reconstruction. These findings encourage implementation of sensory nerve coaptation in standard clinical care.

PGC-1α Inhibits Schwann Cell Dedifferentiation and Delays Peripheral Nerve Degeneration by Targeting PON1.

PPARγ coactivator-1 alpha (PGC-1α) is an essential transcription factor co-activator that regulates gene transcription and neural regeneration. Schwann cells, which are unique glial cells in peripheral nerves that dedifferentiate after peripheral nerve injury (PNI) and are released from degenerative nerves. Wallerian degeneration is a series of stereotypical events that occurs in response to nerve fibers after PNI. The role of PGC-1α in Schwann cell dedifferentiation and Wallerian degeneration is not yet clear. As Wallerian degeneration plays a crucial role in PNI, we conducted a study to determine whether PGC-1α has an effect on peripheral nerve degeneration after injury. We examined the expression of PGC-1α after sciatic nerve crush or transection using Western blotting and found that PGC-1α expression increased after PNI. Then we utilized ex vivo and in vitro models to investigate the effects of PGC-1α inhibition and activation on Schwann cell dedifferentiation and nerve degeneration. Our findings indicate that PGC-1α negatively regulates Schwann cell dedifferentiation and nerve degeneration. Through the use of RNA-seq, siRNA/plasmid transfection and reversal experiments, we identified that PGC-1α targets inhibit the expression of paraoxonase 1 (PON1) during Schwann cell dedifferentiation in degenerated nerves. In summary, PGC-1α plays a crucial role in preventing Schwann cell dedifferentiation and its activation can reduce peripheral nerve degeneration by targeting PON1. PGC-1α inhibits Schwann cell dedifferentiation and peripheral nerve degeneration. PGC-1α negatively regulates Schwann cell dedifferentiation and peripheral nerve degeneration after injury by targeting PON1.

Tuina therapy promotes behavioral improvement and brain plasticity in rats with peripheral nerve injury and repair.

Tuina is currently one of the popular complementary and alternative methods of rehabilitation therapy. Tuina can improve patients' pain and mobility function. However, the underlying physiological mechanism remains largely unknown, which might limit its further popularization in clinical practice. The aim of this study is to explore the short-term and long-term changes in brain functional activity following Tuina intervention for peripheral nerve injury repair. A total of 16 rats were equally divided into the intervention group and the control group. Rats in the intervention group received Tuina therapy applying on the gastrocnemius muscle of the right side for 4 months following sciatic nerve transection and immediate repair, while the control group received nerve transection and repair only. The block-design functional magnetic resonance imaging scan was applied in both groups at 1 and 4 months after the surgery. During the scan, both the injured and intact hindpaw was electrically stimulated according to a "boxcar" paradigm. When stimulating the intact hindpaw, the intervention group exhibited significantly lower activation in the somatosensory area, limbic/paralimbic areas, pain-regulation areas, and basal ganglia compared to the control group, with only the prefrontal area showing higher activation. After 4 months of sciatic nerve injury, the control group exhibited decreased motor cortex activity compared to the activity observed at 1 month, and the intervention group demonstrated stronger bilateral motor cortex activity compared to the control group. Tuina therapy on the gastrocnemius muscle of rats with sciatic nerve injury can effectively alleviate pain and maintain the motor function of the affected limb. In addition, Tuina therapy reduced the activation level of pain-related brain regions and inhibited the decreased activity of the motor cortex caused by nerve injury, reflecting the impact of peripheral stimulation on brain plasticity.