Electromyographic biofeedback training in a cerebral palsy patient undergoing pronator teres rerouting and brachioradialis to extensor carpi radialis brevis tendon transfer surgery: A case report.

Several surgical procedures are used to treat dynamic pronation position of the forearm and flexion deformity of the wrist in cerebral palsy. Postoperative results of pronator teres rerouting were explored, while specially designed postoperative physiotherapy and its outcomes were limited. Herein, we present a case in whom the outcomes of electromyographic biofeedback (EMG-BF) training were assessed after pronator teres rerouting and brachioradialis tendon to extensor carpi radialis brevis tendon transfer combined with derotation osteotomy. The peak value increased, while the resting value decreased for the muscles after the intervention. Range of motion, hand function, manual ability, functional independence, and quality of life levels were improved. In conclusion, EMG biofeedback training may have a positive effect on neuromuscular control of pronator teres and brachioradialis. Free use of the upper extremity and improved manual ability positively affect the activity and quality of life of the patients.

Relationships between the global symptom score and electrophysiological findings after surgical release for carpal tunnel syndrome: Indications and outcomes.

PURPOSE: Regarding surgical indications for carpal tunnel syndrome (CTS), the hypothesis that the recovery processes of subjective symptoms differ among pain, sensory, and motor symptoms and correlate with recovery in objective nerve conduction studies was examined in the present study. METHODS: The global symptom score (GSS) is a method used to assess clinical outcomes and covers subjective symptoms, including pain (pain and nocturnal awakening), sensory (numbness and paresthesia), and motor (weakness/clumsiness) symptoms. The relationships between long-term changes in GSS and recovery in nerve conduction studies were investigated. RESULTS: Forty patients (40 hands) were included (mean age 65 years; 80% female; 68% with moderate CTS: sensory nerve conduction velocity < 45 m/s and motor nerve distal latency > 4.5 ms). Pain and nocturnal awakening rapidly subsided within 1 month after surgery and did not recur in the long term (median 5.6 years). Paresthesia significantly decreased 3 months after surgery and in the long term thereafter. Weakness/clumsiness significantly decreased at 1 year. Sensory nerve distal latency, conduction velocity, and amplitude significantly improved 3 months and 1 year after surgery, and correlated with nocturnal awakening in the short term (3 months) in moderate CTS cases. The patient satisfaction rate was 91%. CONCLUSION: Rapid recovery was observed in pain and nocturnal awakening, of which nocturnal awakening correlated with the recovery of sensory nerve conduction velocity. Patients with pain symptoms due to moderate CTS may benefit from surgical release.

The investigation of effect on foot plantar massage on functional recovery in older adults with general surgery, randomized clinical trial.

OBJECTIVE: Foot massage is known to be effective on the emotional state (anxiety, depression, etc.) in the postoperative period. However, studies on its effect on functional level are insufficient. AIM: The study aimed to investigate the impact of foot plantar massage on functional recovery in older adults undergoing general surgery, employing a randomized clinical trial design. METHODS: A total of 70 older adults aged 65 years and above who underwent abdominal surgery were included. Various assessments were conducted, including pain levels (Visual Analogue Scale), fear of mobility (Tampa Scale for Kinesiophobia), functional independence (Functional Independence Measure), balance (Berg Balance Scale), basic mobility (Rivermead Mobility Index), mental function status (Standardized Mini-Mental State Examination), and delirium (Nu-DESC). RESULTS: Statistically significant differences were observed in some assessment parameters within the groups during the 2nd and 3rd measurement times, with the intervention group demonstrating significant mean differences. DISCUSSIONS: The literature underscores the increase in kinesiophobia scores post-general/abdominal surgery in older adults, emphasizing the importance of evaluating functional level and kinesiophobia to expedite discharge processes and potentially plan early post-discharge rehabilitation to mitigate readmissions for functional reasons. CONCLUSIONS: Ultimately, foot massage was found to be effective in reducing kinesiophobia, improving balance, mobility, daily living skills, and mental status in older adults post-abdominal surgery, thereby advocating for the facilitation of post-discharge rehabilitation programs or the reduction of readmission rates. THE CLINICAL TRIALS NUMBER: NCT05534490.

Recovery of turning speed in patients after vestibular schwannoma resection.

BACKGROUND: Individuals after a vestibular schwannoma resection (VSR) experience significant vestibular symptoms that can be provoked with turning. Vestibular rehabilitation assists in recovery of function and symptom relief, however turning response is unknown. OBJECTIVE: Examine peak turning speed response to surgery and rehabilitation. METHODS: Eight participants with a vestibular schwannoma (PwVS) and five healthy controls (HC) participated in this study. Peak turning speed (PTS) was captured with inertial measurement units (IMU) at the head and/or trunk during turning tasks at a pre-operative, post-operative and post-treatment assessment. Vestibular rehabilitation was provided twice weekly for six weeks. Linear mixed models were used to assess change in PTS across time points. RESULTS: PwVS performed slower PTS than HC prior to surgery. PTS was significantly slower post-operatively compared to pre-operative during walking with head turns (B = -61.03, p = 0.004), two-minute walk test (B = -37.33, p = 0.015), 360° turn (B range from 50.05 to -57.4, p < 0.05) and complex turning course (CTC) at the trunk (B = -18.63, p = 0.009). Post-treatment PTS was significantly faster than pre-operative during CTC at the head (B = 18.46, p = 0.014) and trunk (B = 15.99, p = 0.023). CONCLUSION: PwVS may have turning deficits prior to surgical resection. PTS was significantly affected post-operatively, however improved with rehabilitation.

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice.

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated. METHODS: C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism. RESULTS: Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3-5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH. CONCLUSIONS: Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.

Preoperative handgrip strength can predict early postoperative shoulder function in patients undergoing arthroscopic rotator cuff repair.

BACKGROUND: Rotator cuff tears (RCTs) are a common musculoskeletal disorder, and arthroscopic rotator cuff repair (ARCR) is widely performed for tendon repair. Handgrip strength correlates with rotator cuff function; however, whether preoperative grip strength can predict functional outcomes in patients undergoing ARCR remains unknown. This study aimed to investigate the correlation between preoperative grip strength and postoperative shoulder function following ARCR. METHODS: A total of 52 patients with full-thickness repairable RCTs were prospectively enrolled. Baseline parameters, namely patient characteristics and intraoperative findings, were included for analysis. Postoperative shoulder functional outcomes were assessed using the Quick Disabilities of the Arm, Shoulder, and Hand (QDASH) questionnaire and Constant-Murley scores (CMSs). Patients were followed up and evaluated at three and six months after ARCR. The effects of baseline parameters on postoperative outcomes were measured using generalized estimating equations. RESULTS: At three and six months postoperatively, all clinical outcomes evaluated exhibited significant improvement from baseline following ARCR. Within 6 months postoperatively, higher preoperative grip strength was significantly correlated with higher CMSs (ß = 0.470, p = 0.022), whereas increased numbers of total suture anchors were significantly correlated with decreased CMSs (ß = - 4.361, p = 0.03). Higher body mass index was significantly correlated with higher postoperative QDASH scores (ß = 1.561, p = 0.03) during follow-up. CONCLUSIONS: Higher baseline grip strength predicts more favorable postoperative shoulder function following ARCR. A preoperative grip strength test in orthopedic clinics may serve as a predictor for postoperative shoulder functional recovery in patients undergoing ARCR.

Nrdp1-mediated Macrophage Phenotypic Regulation Promotes Functional Recovery in Mice with Mild Neurological Impairment after Intracerebral Hemorrhage.

Neuregulin receptor degradation protein 1 (Nrdp1) is a ring finger E3 ubiquitin ligase involved in some inflammation through ubiquitination, including macrophage polarization following cerebral hemorrhage. However, there is limited understanding regarding the mechanisms through which Nrdp1 modulates macrophage polarization and the potential impact of this modulation on neurological function. Using stereotactic injection and adenoviral transfection techniques, the corresponding animal models were constructed through injecting adenovirus, saline, or blood into the mouse striatum at different periods of time in this research. The alteration in the ratio of various M1/M2 phenotype-associated markers (e.g., CD86, CD206, IL-6, IL-10, etc.) was evaluated through immunohistochemistry, immunofluorescence, western blotting, and elisa assays. Additionally, neurological function scores and behavioral tests were utilized to evaluate changes in neurological function in mice after cerebral hemorrhage. Our results show that overexpression of Nrdp1 promotes the expression of a variety of M2 macrophage-associated markers and enhance transcriptional activity of arginase-1 (Arg1) protein through ubiquitination for early regulation M2 macrophage polarization. Additionally, Nrdp1 promotes hematoma absorption, increases IL-10 expression, inhibits inducible nitric oxide synthase (iNOS), IL-6, and TNF-α production, alleviates neurological impairment and brain edema, and accelerates functional recovery. These findings suggest that modulating macrophage polarization through Nrdp1 could be a therapeutic strategy for neurofunctional impairment in cerebral hemorrhage.

Mechanism of Fat Mass and Obesity-Related Gene-Mediated Heme Oxygenase-1 m6A Modification in the Recovery of Neurological Function in Mice with Spinal Cord Injury.

OBJECTIVES: This study examined the mechanism of fat mass and obesity-related gene (FTO)-mediated heme oxygenase-1 (HO-1) m6A modification facilitating neurological recovery in spinal cord injury (SCI) mice. FTO/HO-1 was identified as a key regulator of SCI as well as a potential target for treatment of SCI. METHODS: An SCI mouse was treated with pcDNA3.1-FTO/pcDNA3.1-NC/Dac51. An oxygen/glucose deprivation (OGD) cell model simulated SCI, with cells treated with pcDNA3.1-FTO/si-HO-1/Dac51. Motor function and neurobehavioral evaluation were assessed using the Basso, Beattie, and Bresnahan (BBB) scale and modified neurological severity score (mNSS). Spinal cord pathology and neuronal apoptosis were assessed. Further, FTO/HO-1 mRNA and protein levels, HO-1 mRNA stability, the interaction of YTHDF2 with HO-1 mRNA, neuronal viability/apoptosis, and HO-1 m6A modification were evaluated. RESULTS: Spinal cord injury mice exhibited reduced BBB, elevated mNSS scores, disorganized spinal cord cells, scattered nuclei, and severe nucleus pyknosis. pcDNA3.1-FTO elevated FTO mRNA, protein expression, and BBB score; reduced the mNSS score of SCI mice; decreased neuronal apoptosis; improved the cell arrangement; and improved nucleus pyknosis in spinal cord tissues. OGD decreased FTO expression. FTO upregulation ameliorated OGD-induced neuronal apoptosis. pcDNA3.1-FTO reduced HO-1 mRNA and protein and HO-1 m6A modification, while increasing HO-1 mRNA stability and FTO in OGD-treated cells. FTO upregulated HO-1 by modulating m6A modification. HO-1 downregulation attenuated the effect of FTO. pcDNA3.1-FTO/Dac51 increased the HO-1 m6A level in mouse spinal cord tissue homogenate, reduced BBB, boosted mNSS scores of SCI mice, aggravated nucleus pyknosis, and increased neuronal apoptosis in spinal cord tissues, confirming that FTO mediated HO-1 m6A modification facilitated neurological recovery in SCI mice. CONCLUSION: The fat mass and obesity-related gene modulates HO-1 mRNA stability by regulating m6A modification levels, thereby influencing HO-1 expression and promoting neurological recovery in SCI mice.

Appropriate dosage, timing, and site of intramuscular injections of brain-derived neurotrophic factor (BDNF) promote motor recovery after facial nerve injury in rats.

INTRODUCTION/AIMS: Daily intramuscular injections of fibroblast growth factor 2 (FGF2) but not of brain-derived neurotrophic factor (BDNF) significantly improve whisking behavior and mono-innervation of the rat levator labii superioris (LLS) muscle 56 days after buccal nerve transection and suture (buccal-buccal anastomosis, BBA). We explored the dose-response of BDNF, FGF2, and insulin growth factor 2 (IGF2) on the same parameters, asking whether higher doses of BDNF would promote recovery. METHODS: After BBA, growth factors were injected (30 µL volume) daily into the LLS muscle over 14, 28, or 56 days. At 56 days, video-based motion analysis of vibrissal whisking was performed and the extent of mono- and poly-reinnervation of the reinnervated neuromuscular junctions (NMJs) of the muscle determined with immunostaining of the nerve with ß-tubulin and histochemical staining of the endplates with Alexa Fluor 488-conjugated α-bungarotoxin. RESULTS: The dose-response curve demonstrated significantly higher whisking amplitudes and corresponding increased mono-innervation of the NMJ in the reinnervated LLS muscle at concentrations of 20-30 µg/mL BDNF administered daily for 14-28 days after BBA surgery. In contrast, high doses of IGF2 and FGF2, or doses of 20 and 40 µg/mL of BDNF administered for 14-56 days had no effect on either whisking behavior or in reducing poly-reinnervation of endplates in the muscle. DISCUSSION: These data suggest that the re-establishment of mono-innervation of whiskerpad muscles and the improved motor function by injections of BDNF into the paralyzed vibrissal musculature after facial nerve injury have translation potential and promote clinical application.

Osteopontin Promotes Angiogenesis in the Spinal Cord and Exerts a Protective Role Against Motor Function Impairment and Neuropathic Pain After Spinal Cord Injury.

STUDY DESIGN: Basic science study using a hemisection spinal cord injury (SCI) model. OBJECTIVE: We sought to assess the effect of blocking osteopontin (OPN) upregulation on motor function recovery and pain behavior after SCI and to further investigate the possible downstream target of OPN in the injured spinal cord. SUMMARY OF BACKGROUND DATA: OPN is a noncollagenous extracellular matrix protein widely expressed across different tissues. Its expression substantially increases following SCI. A previous study suggested that this protein might contribute to locomotor function recovery after SCI. However, its neuroprotective potential was not fully explored, nor were the underlying mechanisms. MATERIALS AND METHODS: We constructed a SCI mouse model and analyzed the expression of OPN at different time points and the particular cell distribution in the injured spinal cord. Then, we blocked OPN upregulation with lentivirus-delivering siRNA targeting OPN specifically and examined its effect on motor function impairment and neuropathic pain after SCI. The underlying mechanisms were explored in the OPN-knockdown mice model and cultured vascular endothelial cells. RESULTS: The proteome study revealed that OPN was the most dramatically increased protein following SCI. OPN in the spinal cord was significantly increased three weeks after SCI. Suppressing OPN upregulation through siRNA exacerbated motor function impairment and neuropathic pain. In addition, SCI resulted in an increase in vascular endothelial growth factor (VEGF), AKT phosphorylation, and angiogenesis within the spinal cord, all of which were curbed by OPN reduction. Similarly, OPN knockdown suppressed VEGF expression, AKT phosphorylation, cell migration, invasion, and angiogenesis in cultured vascular endothelial cells. CONCLUSION: OPN demonstrates a protective influence against motor function impairment and neuropathic pain following SCI. This phenomenon may result from the proangiogenetic effect of OPN, possibly due to activation of the VEGF and/or AKT pathways.

AAV-mediated VEGFA overexpression promotes angiogenesis and recovery of locomotor function following spinal cord injury via PI3K/Akt signaling.

Spinal cord injury (SCI) is a disorder of the central nervous system resulting from various factors such as trauma, inflammation, tumors, and other etiologies. This condition leads to impairment in motor, sensory, and autonomic functions below the level of injury. Limitations of current therapeutic approaches prompt an investigation into therapeutic angiogenesis through persistent local expression of proangiogenic factors. Here, we investigated whether overexpression of adeno-associated virus (AAV)-mediated vascular endothelial growth factor A (VEGFA) in mouse SCI promoted locomotor function recovery, and whether the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was mechanistically involved. Three weeks before SCI, AAV-VEGFA was injected at the T10 level to induce VEGFA overexpression. Neurofunctional, histological, and biochemical assessments were done to determine tissue damage and/or recovery of neuromuscular and behavioral impairments. Daily injections of the PI3K/Akt pathway inhibitor LY294002 were made to assess a possible mechanism. AAV-VEGFA overexpression dramatically improved locomotor function and ameliorated pathological injury caused by SCI. Improved motor-evoked potentials in hindlimbs and more spinal CD31-positive microvessels were observed in AAV-VEGFA-overexpressing mice. LY294002 reduced PI3K and Akt phosphorylation levels and attenuated AAV-VEGFA-related improvements. In conclusion, sustained local AAV-mediated VEGFA overexpression in spinal cord can significantly promote angiogenesis and ameliorate locomotor impairment after SCI in a contusion mouse model through activation of the PI3K/Akt signaling pathway.

Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury.

The transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise in spinal cord injury (SCI) model animals. Establishing a functional synaptic connection between the transplanted and host neurons is crucial for motor function recovery. To boost therapeutic outcomes, we developed an ex vivo gene therapy aimed at promoting synapse formation by expressing the synthetic excitatory synapse organizer CPTX in hiPSC-NS/PCs. Using an immunocompromised transgenic rat model of SCI, we evaluated the effects of transplanting CPTX-expressing hiPSC-NS/PCs using histological and functional analyses. Our findings revealed a significant increase in excitatory synapse formation at the transplantation site. Retrograde monosynaptic tracing indicated extensive integration of transplanted neurons into the surrounding neuronal tracts facilitated by CPTX. Consequently, locomotion and spinal cord conduction significantly improved. Thus, ex vivo gene therapy targeting synapse formation holds promise for future clinical applications and offers potential benefits to individuals with SCI.

GPNMB Modulates Autophagy to Enhance Functional Recovery After Spinal Cord Injury in Rats.

Spinal cord injury (SCI) severely affects the quality of life and autonomy of patients, and effective treatments are currently lacking. Autophagy, an essential cellular metabolic process, plays a crucial role in neuroprotection and repair after SCI. Glycoprotein non-metastatic melanoma protein B (GPNMB) has been shown to promote neural regeneration and synapse reconstruction, potentially through the facilitation of autophagy. However, the specific role of GPNMB in autophagy after SCI is still unclear. In this study, we utilized the spinal cord transection method to establish SCI rats model and overexpressed GPNMB using adenoviral vectors. We assessed tissue damage using hematoxylin and eosin (H&E) and Nissl staining, and observed cell apoptosis using TUNEL staining. We evaluated the inflammatory response by measuring inflammatory factors using enzyme-linked immunosorbent assay (ELISA). In addition, we measured reactive oxygen species (ROS) levels using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and assessed oxidative stress levels by measuring malondialdehyde (MDA) and glutathione (GSH) using ELISA. To evaluate autophagy levels, we performed immunofluorescence staining for the autophagy marker Beclin-1 and conducted Western blot analysis for autophagy-related proteins. We also assessed limb recovery through functional evaluation. Meanwhile, we induced cell injury using lipopolysaccharide (LPS) and added an autophagy inhibitor to verify the impact of GPNMB on SCI through autophagy modulation. The results demonstrated that GPNMB alleviated the inflammatory response, reduced oxidative stress levels, inhibited cell apoptosis, and promoted autophagy following SCI. Inhibiting autophagy reversed the effects of GPNMB. These findings suggest that GPNMB promotes neural injury repair after SCI, potentially through attenuating the inflammatory response, reducing oxidative stress, and inhibiting cell apoptosis.

Efficacy of growth factor gene-modified stem cells for motor function after spinal cord injury in rodents: a systematic review and meta­analysis.

The efficacy of growth factor gene-modified stem cells in treating spinal cord injury (SCI) remains unclear. This study aims to evaluate the effectiveness of growth factor gene-modified stem cells in restoring motor function after SCI. Two reviewers searched four databases, including PubMed, Embase, Web of Science, and Scopus, to identify relevant records. Studies on rodents assessing the efficacy of transplanting growth factor gene-modified stem cells in restoring motor function after SCI were included. The results were reported using the standardized mean difference (SMD) with a 95% confidence interval (95% CI). Analyses showed that growth factor gene-modified stem cell transplantation improved motor function recovery in rodents with SCI compared to the untreated (SMD = 3.98, 95% CI 3.26-4.70, I2 = 86.8%, P < 0.0001) and stem cell (SMD = 2.53, 95% CI 1.93-3.13, I2 = 86.9%, P < 0.0001) groups. Using growth factor gene-modified neural stem/histone cells enhanced treatment efficacy. In addition, the effectiveness increased when viral vectors were employed for gene modification and high transplantation doses were administered during the subacute phase. Stem cells derived from the human umbilical cord exhibited an advantage in motor function recovery. However, the transplantation of growth factor gene-modified stem cells did not significantly improve motor function in male rodents (P = 0.136). Transplantation of growth factor gene-modified stem cells improved motor function in rodents after SCI, but claims of enhanced efficacy should be approached with caution. The safety of gene modification remains a significant concern, requiring additional efforts to enhance its clinical translatability.

Chronic Spinal Cord Injury Regeneration with Combined Therapy Comprising Neural Stem/Progenitor Cell Transplantation, Rehabilitation, and Semaphorin 3A Inhibitor.

Spinal cord injury (SCI) often results in various long-term sequelae, and chronically injured spinal cords exhibit a refractory feature, showing a limited response to cell transplantation therapies. To our knowledge, no preclinical studies have reported a treatment approach with results surpassing those of treatment comprising rehabilitation alone. In this study of rats with SCI, we propose a novel combined therapy involving a semaphorin 3A inhibitor (Sema3Ai), which enhances axonal regeneration, as the third treatment element in combination with neural stem/progenitor cell transplantation and rehabilitation. This comprehensive therapeutic strategy achieved significant improvements in host-derived neuronal and oligodendrocyte differentiation at the SCI epicenter and promoted axonal regeneration even in the chronically injured spinal cord. The elongated axons established functional electrical connections, contributing to significant enhancements in locomotor mobility when compared with animals treated with transplantation and rehabilitation. As a result, our combined transplantation, Sema3Ai, and rehabilitation treatment have the potential to serve as a critical step forward for chronic SCI patients, improving their ability to regain motor function.

Trigeminal or peripheral nerve stimulation improves functional outcomes of nerve recovery in a rodent forelimb gap repair model.

BACKGROUND: The hypothesis of this study was that trigeminal nerve stimulation (TNS) or peripheral nerve stimulation (PNS) could improve functional outcomes of peripheral nerve injury in a rat forelimb model when compared to control rats not receiving electrical stimulation (ES). While PNS is known to improve outcomes after nerve surgery, the role of TNS has not been explored. METHODS: Lewis rats were trained to perform a reach and grasp task before receiving a 2 mm gap repair of the ulnar and median nerves and randomized into four treatment groups: (1) sham injury, (2) nerve injury with sham ES, (3) nerve injury with PNS, and (4) nerve injury with TNS. Functional motor (median pull force and percent success in motor task) and sensory metrics (forelimb paw withdrawal thresholds) were collected both pre-injury and throughout rehabilitation. Nerves stained using Gomori's trichrome were assessed quantitatively and qualitatively. RESULTS: The sham ES group did not recover their pre-injury baseline functional outcomes. In contrast, the TNS and PNS groups fully recovered following injury, with no difference in functional outcomes between the pre-injury baseline and the final week of rehabilitation (P > 0.05, all). Histomorphology results demonstrated no quantitative difference, but qualitative differences in architecture were evident. CONCLUSIONS: Electrical stimulation of the trigeminal nerve or the injured nerve improved the functional outcomes of nerve regeneration in rodents. Histomorphology results of nerves from the TNS group support the proposed central mechanisms. This is an important step in translating this therapy as an adjunct, non-invasive treatment for high, mixed nerve injuries in humans.

Myelin repair of spinal cord injury in adult mice induced by treadmill training upregulated peroxisome proliferator-activated receptor gamma coactivator 1 alpha.

Growing evidence has proven the efficacy of physical exercise in remyelination and motor function performance after spinal cord injury (SCI). However, the molecular mechanisms of treadmill training on myelin repair and functional recovery after SCI have not yet been fully studied. Here, we explored the effect of treadmill training on upregulating peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α)-mediated myelin repair and functional recovery in a mouse model of thoracic T10 contusion injury. A 4-week treadmill training scheme was conducted on mice with SCI. The expression levels of oligodendrogenesis-related protein and PGC1α were detected by immunofluorescence, RNA fluorescence in situ hybridization and western blotting. Transmission electron microscopy (TEM) was used to observe myelin structure. The Basso Mouse Scale (BMS) and CatWalk automated gait analysis system were used for motor function recovery evaluation. Motor evoked potentials (MEPs) were also identified. In addition, adeno-associated virus (AAV)-mediated PGC1α knockdown in OLs was used to further unravel the role of PGC1α in exercise-induced remyelination. We found that treadmill training boosts oligodendrocyte precursor cells (OPCs) proliferation, potentiates oligodendrocytes (OLs) maturation, and increases myelin-related protein and myelin sheath thickness, thus impelling myelin repair and hindlimb functional performance as well as the speed and amplitude of nerve conduction after SCI. Additionally, downregulating PGC1α through AAV attenuated these positive effects of treadmill training. Collectively, our results suggest that treadmill training enhances remyelination and functional recovery by upregulating PGC1α, which should provide a step forward in the understanding of the effects of physical exercise on myelin repair.

Key Considerations for Nerve Transfer Rehabilitation After Surgical Reconstruction for Brachial Plexus and Peripheral Nerve Injuries.

Nerve transfer surgery is commonly used to treat patients with brachial plexus injuries. However, guidelines on postoperative rehabilitation are not clearly established. Nerve transfers require the patient to relearn how to recruit newly innervated muscle(s), which may not occur naturally or intuitively. Supervised therapy is a valuable resource to guide patients through their lengthy recovery (often >12 months) because target muscle strength is both obtained and functionally used in daily life. This article highlights 10 key principles that provide the foundation for rehabilitation following nerve transfer surgery after a brachial plexus injury. Due to the shortcomings of the current evidence base for nerve transfer rehabilitation, we have included our anecdotal experience to augment the existing literature. It is important to have a collaborative surgeon-therapist relationship to communicate regarding operative details, expected timelines for reinnervation, patient needs, and realistic expectations. We provide examples of how to tailor the exercise program to synergistically recruit both the donor and target muscle action, including how to appropriately advance exercises based on the current level of nerve return. We also discuss the role that fatigue plays in denervated muscle and how fatigue may affect the exercise demands placed on the target muscle during specific stages of recovery.

[Effect and mechanism of Zuogui Pills on neural function recovery in ischemic stroke mice based on OPN/IGF-1/mTOR].

To explore the effect and mechanism of Zuogui Pills in promoting neural tissue recovery and functional recovery in mice with ischemic stroke. Male C57BL/6J mice were randomly divided into a sham group, a model group, and low-, medium, and high-dose Zuogui Pills groups(3.5, 7, and 14 g·kg~(-1)), with 15 mice in each group. The ischemic stroke model was established using photochemical embolization. Stiker remove and irregular ladder walking behavioral tests were conducted before modeling and on days 7, 14, 21, and 28 after medication. Triphenyl tetrazolium chloride(TTC) staining was performed on day 3 after modeling, and T2-weighted imaging(T2WI) and diffusion-weighted imaging(DWI) were performed on day 28 after medication to evaluate the extent of brain injury. Hematoxylin-eosin(HE) staining was performed to observe the histology of the cerebral cortex. Axonal marker proteins myelin basic protein(MBP), growth-associated protein 43(GAP43), mammalian target of rapamycin(mTOR), and its downstream phosphorylated s6 ribosomal protein(p-S6), as well as mechanism-related proteins osteopontin(OPN) and insulin-like growth factor 1(IGF-1), were detected using immunofluorescence and Western blot. Zuogui Pills had a certain restorative effect on the neural function impairment caused by ischemic stroke in mice. TTC staining showed white infarct foci in the sensory-motor cortex area, and T2WI imaging revealed cystic necrosis in the sensory-motor cortex area. The Zuogui Pills groups showed less brain tissue damage, fewer scars, and more capillaries. The number of neuronal axons in those groups was higher than that in the model group, and neuronal activity was stronger. The expression of GAP43, OPN, IGF-1, and mTOR proteins in the Zuogui Pills groups was higher than that in the model group. In summary, Zuogui Pills can promote the recovery of neural function and axonal growth in mice with ischemic stroke, and its mechanism may be related to the activation of the OPN/IGF-1/mTOR signaling pathway.

Glycine and N-Acetylcysteine (GlyNAC) Combined with Body Weight Support Treadmill Training Improved Spinal Cord and Skeletal Muscle Structure and Function in Rats with Spinal Cord Injury.

Skeletal muscle atrophy is a frequent complication after spinal cord injury (SCI) and can influence the recovery of motor function and metabolism in affected patients. Delaying skeletal muscle atrophy can promote functional recovery in SCI rats. In the present study, we investigated whether a combination of body weight support treadmill training (BWSTT) and glycine and N-acetylcysteine (GlyNAC) could exert neuroprotective effects, promote motor function recovery, and delay skeletal muscle atrophy in rats with SCI, and we assessed the therapeutic effects of the double intervention from both a structural and functional viewpoint. We found that, after SCI, rats given GlyNAC alone showed an improvement in Basso-Beattie-Bresnahan (BBB) scores, gait symmetry, and results in the open field test, indicative of improved motor function, while GlyNAC combined with BWSTT was more effective than either treatment alone at ameliorating voluntary motor function in injured rats. Meanwhile, the results of the skeletal muscle myofiber cross-sectional area (CSA), hindlimb grip strength, and acetylcholinesterase (AChE) immunostaining analysis demonstrated that GlyNAC improved the structure and function of the skeletal muscle in rats with SCI and delayed the atrophication of skeletal muscle.