OBJECTIVE: To investigate the effect of folic acid coated-crosslinked urethane-doped polyester elastomer (fCUPE) nerve conduit in repairing long distance peripheral nerve injury. METHODS: Thirty-six 3-month-old male Sprague Dawley rats weighing 180-220 g were randomly assigned to 3 groups, each consisting of 12 rats: CUPE nerve conduit transplantation group (group A), fCUPE nerve conduit transplantation group (group B), and autologous nerve transplantation group (group C), the contralateral healthy limb of group C served as the control group (group D). A 20-mm-long sciatic nerve defect model was established in rats, and corresponding materials were used to repair the nerve defect according to the group. The sciatic function index (SFI) of groups A-C was calculated using the Bain formula at 1, 2, and 3 months after operation. The nerve conduction velocity (NCV) of the affected side in groups A-D was assessed using neuroelectrophysiological techniques. At 3 months after operation, the regenerated nerve tissue was collected from groups A-C for S-100 immunohistochemical staining and Schwann cell count in groups A and B to compare the level of nerve repair and regeneration in each group. RESULTS: At 3 months after operation, the nerve conduits in all groups partially degraded. There was no significant adhesion between the nerve and the conduit and the surrounding tissues, the conduit was well connected with the distal and proximal nerves, and the nerve-like tissues in the conduit could be observed when the nerve conduit stents were cut off. SFI in group A was significantly higher than that in group C at each time point after operation and was significantly higher than that in group B at 2 and 3 months after operation ( P<0.05). There was no significant difference in SFI between groups B and C at each time point after operation ( P>0.05). NCV in group A was significantly slower than that in the other 3 groups at each time point after operation ( P<0.05). The NCV of groups B and C were slower than that of group D, but the difference was significant only at 1 month after operation ( P<0.05). There was no significant difference between groups B and C at each time point after operation ( P>0.05). Immunohistochemical staining showed that the nerve tissue of group A had an abnormal cavo-like structure, light tissue staining, and many non-Schwann cells. In group B, a large quantity of normal neural structures was observed, the staining was deeper than that in group A, and the distribution of dedifferentiated Schwann cells was obvious. In group C, the nerve bundles were arranged neatly, and the tissue staining was the deepest. The number of Schwann cells in group B was (727.50±57.60) cells/mm ², which was significantly more than that in group A [(298.33±153.12) cells/mm ²] ( t=6.139, P<0.001). CONCLUSION The fCUPE nerve conduit is effective in repairing long-distance sciatic nerve defects and is comparable to autologous nerve grafts. It has the potential to be used as a substitute material for peripheral nerve defect transplantation.
Rats ; Animals ; Male ; Rats, Sprague-Dawley ; Polyesters ; Peripheral Nerve Injuries/surgery* ; Elastomers ; Urethane ; Sciatic Nerve/injuries* ; Carbamates ; Nerve Tissue ; Nerve Regeneration/physiology*

OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) combined with neurodynamic mobilization (NM) on the cross-sectional area of the gastrocnemius muscle fibers after sciatic nerve injury in rabbits, and the expression of nuclear factor κB (NF-κB) and muscle-specific ring-finger protein 1 (MuRF1). METHODS: A total of 180 common-grade New Zealand rabbits (half male and half female) were randomly divided into five groups, i.e. a normal control group, a model control group, a NM group, an EA group and a combined intervention group, 36 rabbits in each group. Except in the normal control group, clipping method was used to prepare the model of sciatic nerve injury in the rest groups. On the 3rd day of successful modeling, NM was delivered in the NM group. In the EA group, EA was exerted at bilateral "Jiaji" (EX-B 2) of L₄ to L₆, stimulated with disperse-dense wave and the frequency of 2 Hz/100 Hz. In the combined intervention group, after EA delivered at bilateral "Jiaji" (EX-B 2) of L₄ to L₆ , NM was operated. The intervention in each group was delivered once daily, for 6 days a week, and lasted 1, 2 or 4 weeks according to the collection time of sample tissue. After 1, 2 and 4 weeks of intervention, in each group, the toe tension reflex score and the modified Tarlov test score were observed; the morphology of the gastrocnemius muscle was observed by HE staining and the cross-sectional area of muscular fiber was measured; using Western blot method, the expression of NF-κB and MuRF1 of the gastrocnemius muscle was detected. RESULTS: After 1, 2 and 4 weeks of intervention, the toe tension reflex scores and the modified Tarlov scores in the model control group were lower than those of the normal control group (P<0.05), and these two scores in the NM group, the EA group and the combined intervention group were all higher than those of the model control group (P<0.05); the scores in the combined intervention group were higher than those in the EA group and the NM group (P<0.05). The gastrocnemius fibers were well arranged and the myocyte morphology was normal in the normal control group. In the model control group, the gastrocnemius fibers were disarranged, the myocytes were irregular in morphology and the inflammatory cells were infiltrated in the local. In the NM group, the EA group and the combined intervention group, the muscle fibers were regularly arranged when compared with the model control group. After 1, 2 and 4 weeks of intervention, the cross-sectional areas of the gastrocnemius muscle fibers in the model control group were smaller than those of the normal control group (P<0.05). The cross-sectional areas in the NM group, the EA group and the combined intervention group were larger than those of the model control group (P<0.05), and the cross-sectional areas in the combined intervention group were larger than those in the NM group and the EA group (P<0.05). After intervention for 1, 2 and 4 weeks, the protein expressions of NF-κB and MuRF1 in the gastrocnemius muscle were higher in the model control group in comparison of those in the normal control group (P<0.05). In the NM group, the EA group and the combined intervention group, the expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were lower when compared with those in the model control group (P<0.05). In the combined intervention group, the protein expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were decreased when compared with those in the NM group and the EA group (P<0.05). CONCLUSIONS Electroacupuncture at "Jiaji" (EX-B 2) combined with NM may increase the muscle strength and sciatic function and alleviate gastrocnemius muscle atrophy in the rabbits with sciatic nerve injury. The underlying mechanism is related to the inhibition of NF-κB and MuRF1 expression.
Animals ; Female ; Male ; Rabbits ; Electroacupuncture ; Muscle, Skeletal ; Muscular Atrophy/therapy* ; NF-kappa B/genetics* ; Peripheral Nerve Injuries ; Rats, Sprague-Dawley ; Sciatic Nerve

OBJECTIVE: To provide useful information for selecting the most appropriate peripheral nerve injury model for different research purposes in nerve injury and repair studies, and to compare nerve regeneration capacity and characteristics between them. METHODS: Sixty adult SD rats were randomly divided into two groups and underwent crush injury alone (group A, n = 30) or transection injury followed by surgical repair (group B, n = 30) of the right hind paw. Each group was subjected to the CatWalk test, gastrocnemius muscle evaluation, pain threshold measurement, electrophysiological examination, retrograde neuronal labeling, and quantification of nerve regeneration before and 7, 14, 21, and 28 days after injury. RESULTS: Gait analysis showed that the recovery speed in group A was significantly faster than that in group B at 14 days. At 21 days, the compound muscle action potential of the gastrocnemius muscle in group A was significantly higher than that in group B, and the number of labeled motor neurons in group B was lower than that in group A. The number of new myelin sheaths and the g-ratio were higher in group A than in group B. There was a 7-day time difference in the regeneration rate between the two injury groups. CONCLUSION The regeneration of nerve fibers was rapid after crush nerve injury, whereas the transection injury was relatively slow, which provides some ideas for the selection of clinical research models.
Animals ; Rats ; Nerve Fibers ; Nerve Regeneration ; Rats, Sprague-Dawley ; Sciatic Nerve/injuries*

Artificial nerve guidance conduits (NGCs) are synthetic nerve grafts that are capable of providing the structural and nutritional support for nerve regeneration. The ideal NGCs have plenty of requirements on biocompatibility, mechanical strength, topological structure, and conductivity. Therefore, it is necessary to continuously improve the design of NGCs and establish a better therapeutic strategy for peripheral nerve injury in order to meet clinical needs. Although current NGCs have made certain process in the treatment of peripheral nerve injury, their nerve regeneration and functional outcomes on repairing long-distance nerve injury remain unsatisfactory. Herein, we review the nerve conduit design from four aspects, namely raw material selection, structural design, therapeutic factor loading and self-powered component integration. Moreover, we summarize the research progress of NGCs in the treatment of peripheral nerve injury, in order to facilitate the iterative updating and clinical transformation of NGCs.
Humans ; Peripheral Nerve Injuries/therapy* ; Guided Tissue Regeneration ; Nerve Regeneration/physiology* ; Sciatic Nerve

OBJECTIVE: To explore lumbar plexus nerve block combined with general anesthesia in elderly patients undergoing hip operation could improve analgesia effect, reduce consumption of analgesics, prevent inflammatory reaction, and avoid postoperative delirium(POD). METHODS: Totally 200 elderly patients underwent hip fracture surgery from February 2020 to September 2021 were selected and were divided into observation group and control group according to different anesthesia methods. There were 97 patients in observation group including 66 males and 33 females; aged (70.23±6.60) years old;body mass index (BMI) was (23.13±1.94) kg·m-2;19 patients with hemi arthroplasty, 46 patients with total hip arthroplasty, and 32 patients with femur intertrochanteric fixation;treated with lumbar plexus block combined with general anesthesia. There were 94 patients in control group, including 66 males and 33 females;aged (68.80±6.24) years old;BMI was (22.88±1.85) kg·m-2;14 patients with hemi arthroplasty, 39 patients with total hip arthroplasty, and 41 patients with femur intertrochanteric fixation;treated with only general anesthesia. Nine patients were separated due to the change of surgical protocol or chronic disease. The incidence of POD at 1, 2 and 3 days after surgery, mini-mental state examination (MMSE) score, visual analogue scale (VAS) in resting state, serum inflammatory factors levels [such as C-reactive protein(CRP), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)] at 1 d before operation, 1 and 6 h after surgery, consumption of sufentanil between two groups were compared. RESULTS: The incidences of POD in observation group were lower than control group at 1, 2 and 3 days of operation (P<0.05), MMSE score in observation group was higher than that of control group (P<0.05), VAS in observation group was lower than that of control group (P<0.01). The incidences of POD decreased and MMSE score were increaed in both groups day by day (P<0.01). The levels of CRP, IL-1β, IL-6 and TNF-α in observation group were lower than that of control group at 1 h after operation (P<0.01). The levels of CRP, IL-6 and TNF-α in observation group were lower than that of control group at 6 h after operation (P<0.01), while no statisitical difference in IL-1β between two groups(P>0.05). The consumption of sufentanil in observation group was lower than that of control group (P<0.01). CONCLUSION Compared with general anesthesia, lumbar plexus nerve block combined with general anesthesia for the operations of hip fracture in elderly patients has better analgesic effect, has advantages of slight inflammatory reaction, and could decrease consumption of opioid and incidence of POD.
Aged ; Female ; Male ; Humans ; Middle Aged ; Emergence Delirium ; Interleukin-6 ; Sufentanil ; Tumor Necrosis Factor-alpha ; Hip Fractures/surgery* ; Anesthesia, General ; Inflammation ; Lumbosacral Plexus

OBJECTIVE: To study the effect of ultrasound-guided fascia iliaca compartment block on perioperative analgesia and postoperative complications in geriatric patients with hip fractures. METHODS: A total of 127 elderly patients undergoing hip fracture surgery from January 2021 to September 2021 were randomized to receive ultrasound-guided continuous fascia iliaca compartment block(group F) either intravenous analgesia control group(group C). There were 62 cases in group F, including 19 males and 43 females with an average age of (82.4±7.2) years old ranging from 66 to 95 years old, involving 25 femoral neck fractures and 37 femoral intertrochanteric fractures. There were 65 cases in control group, including 18 males and 47 females, with an average age of (81.4±8.7) years old ranging from 65 to 94 years old, involving 29 femoral neck fractures and 36 femoral intertrochanteric fractures. The visual analogue scale(VAS), minimental state examination (MMSE), observer's assessment of alertness/sedation(OAA/S) scale, modified Bromage score, postoperative complications and general conditions during hospitalization in two groups were observed. RESULTS: The resting and exercise VAS at 30 min after block, anesthesia placement and 6, 24 and 48 h after surgery were lower than those in group C(P<0.05). In group F, MMSE scores at 12 h before surgery, and 1, 3 d after surgery and OAA/S scores at 3 d after surgery were higher than those in group C(P<0.05). The incidence of adverse effects and the number requiring additional analgesia were lower than those in group C(P<0.05). Group F had better perioperative analgesia satisfaction and hospital stay than group C(P<0.05). But there was no significant difference regarding Bromage score and 30-day mortality between two group(P>0.05). CONCLUSION Ultrasound-guided continuous fascia iliacus space block was safe and effective for elderly patients with hip fracture, and could significantly reduce perioperative pain, improve postoperative cognitive function, and reduce postoperative complications, thereby shortening hospital stay and improving the quality of life during hospitalization.
Male ; Female ; Humans ; Aged ; Aged, 80 and over ; Pain Management ; Nerve Block ; Quality of Life ; Hip Fractures/surgery* ; Pain/surgery* ; Femoral Neck Fractures/surgery* ; Femoral Fractures/surgery* ; Ultrasonography, Interventional ; Postoperative Complications/surgery* ; Fascia ; Pain, Postoperative

The rostral agranular insular cortex (RAIC) has been associated with pain modulation. Although the endogenous cannabinoid system (eCB) has been shown to regulate chronic pain, the roles of eCBs in the RAIC remain elusive under the neuropathic pain state. Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve (CPN) ligation. The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice, glutamatergic, or GABAergic neuron cannabinoid receptor 1 (CB1R) knockdown mice with the whole-cell patch-clamp and pain behavioral methods. The E/I ratio (amplitude ratio between mEPSCs and mIPSCs) was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice. Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice. The analgesic effect of ACEA (a CB1R agonist) was alleviated along with bilateral dorsolateral funiculus lesions, with the administration of AM251 (a CB1R antagonist), and in CB1R knockdown mice in GABAergic neurons, but not glutamatergic neurons of the RAIC. Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.
Mice ; Animals ; Insular Cortex ; Peroneal Nerve ; Mice, Inbred C57BL ; Neuralgia ; GABAergic Neurons ; Analgesia ; Analgesics ; Receptors, Cannabinoid

Rats ; Animals ; Sciatic Neuropathy ; Muscle, Skeletal ; Sciatic Nerve/physiology* ; Sequence Analysis, RNA ; Nerve Regeneration/physiology*

Enhancing remyelination after injury is of utmost importance for optimizing the recovery of nerve function. While the formation of myelin by Schwann cells (SCs) is critical for the function of the peripheral nervous system, the temporal dynamics and regulatory mechanisms that control the progress of the SC lineage through myelination require further elucidation. Here, using in vitro co-culture models, gene expression profiling of laser capture-microdissected SCs at various stages of myelination, and multilevel bioinformatic analysis, we demonstrated that SCs exhibit three distinct transcriptional characteristics during myelination: the immature, promyelinating, and myelinating states. We showed that suppressor interacting 3a (Sin3A) and 16 other transcription factors and chromatin regulators play important roles in the progress of myelination. Sin3A knockdown in the sciatic nerve or specifically in SCs reduced or delayed the myelination of regenerating axons in a rat crushed sciatic nerve model, while overexpression of Sin3A greatly promoted the remyelination of axons. Further, in vitro experiments revealed that Sin3A silencing inhibited SC migration and differentiation at the promyelination stage and promoted SC proliferation at the immature stage. In addition, SC differentiation and maturation may be regulated by the Sin3A/histone deacetylase2 (HDAC2) complex functionally cooperating with Sox10, as demonstrated by rescue assays. Together, these results complement the recent genome and proteome analyses of SCs during peripheral nerve myelin formation. The results also reveal a key role of Sin3A-dependent chromatin organization in promoting myelinogenic programs and SC differentiation to control peripheral myelination and repair. These findings may inform new treatments for enhancing remyelination and nerve regeneration.
Animals ; Axons ; Chromatin/metabolism* ; Gene Expression Profiling ; Myelin Sheath/metabolism* ; Nerve Regeneration/physiology* ; Rats ; Schwann Cells/metabolism* ; Sciatic Nerve/injuries*

OBJECTIVE: It has been reported that local vibration therapy can benefit recovery after peripheral nerve injury, but the optimized parameters and effective mechanism were unclear. In the present study, we investigated the effect of local vibration therapy of different amplitudes on the recovery of nerve function in rats with sciatic nerve injury (SNI). METHODS: Adult male Sprague-Dawley rats were subjected to SNI and then randomly divided into 5 groups: sham group, SNI group, SNI + A-1 mm group, SNI + A-2 mm group, and SNI + A-4 mm group (A refers to the amplitude; n = 10 per group). Starting on the 7th day after model initiation, local vibration therapy was given for 21 consecutive days with a frequency of 10 Hz and an amplitude of 1, 2 or 4 mm for 5 min. The sciatic function index (SFI) was assessed before surgery and on the 7th, 14th, 21st and 28th days after surgery. Tissues were harvested on the 28th day after surgery for morphological, immunofluorescence and Western blot analysis. RESULTS: Compared with the SNI group, on the 28th day after surgery, the SFIs of the treatment groups were increased; the difference in the SNI + A-2 mm group was the most obvious (95% confidence interval [CI]: [5.86, 27.09], P < 0.001), and the cross-sectional areas of myocytes in all of the treatment groups were improved. The G-ratios in the SNI + A-1 mm group and SNI + A-2 mm group were reduced significantly (95% CI: [-0.12, -0.02], P = 0.007; 95% CI: [-0.15, -0.06], P < 0.001). In addition, the expressions of S100 and nerve growth factor proteins in the treatment groups were increased; the phosphorylation expressions of ERK1/2 protein in the SNI + A-2 mm group and SNI + A-4 mm group were upregulated (95% CI: [0.03, 0.96], P = 0.038; 95% CI: [0.01, 0.94], P = 0.047, respectively), and the phosphorylation expression of Akt in the SNI + A-1 mm group was upregulated (95% CI: [0.11, 2.07], P = 0.031). CONCLUSION Local vibration therapy, especially with medium amplitude, was able to promote the recovery of nerve function in rats with SNI; this result was linked to the proliferation of Schwann cells and the activation of the ERK1/2 and Akt signaling pathways.
Animals ; Male ; Peripheral Nerve Injuries/therapy* ; Proto-Oncogene Proteins c-akt/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve/metabolism* ; Sciatic Neuropathy/metabolism* ; Vibration/therapeutic use*