We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To ide...We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To identify the major active component of ABPP, and thus optimize the use of ABPP, we used reverse-phase high performance liquid chromatography to separate ABPP. We obtained 12 fractions, among which the fraction of ABPPk demonstrated the strongest neuroactivity. Immunocytochemistry and western blot analysis showed that ABPPk promoted neurite growth in cultured dorsal root ganglion explant and dorsal root ganglion neurons, which might be associated with activation of Erk1/2. A combination of behavioral tests, electrophysiological assessment, and histomorphometric analysis indicated that ABPPk enhanced nerve regeneration and function restoration in a mouse model of crushed sciatic nerve. All the results suggest that ABPPk, as the key component of ABPP, can be used for peripheral nerve repair to yield better outcomes than ABPP.展开更多
Studies have shown that sensory nerve damage can activate the p38 mitogen-activated protein kinase（MAPK）pathway,but whether the same type of nerve injury after exercise activates the p38MAPK pathway remains unclear....Studies have shown that sensory nerve damage can activate the p38 mitogen-activated protein kinase（MAPK）pathway,but whether the same type of nerve injury after exercise activates the p38MAPK pathway remains unclear.Several studies have demonstrated that nerve growth factor may play a role in the repair process after peripheral nerve injury,but there has been little research focusing on the hypoglossal nerve injury and repair.In this study,we designed and established rat models of hypoglossal nerve crush injury and gave intraperitoneal injections of exogenous nerve growth factor to rats for 14 days.p38MAPK activity in the damaged neurons was increased following hypoglossal nerve crush injury;exogenous nerve growth factor inhibited this increase in acitivity and increased the survival rate of motor neurons within the hypoglossal nucleus.Under transmission electron microscopy,we found that the injection of nerve growth factor contributed to the restoration of the morphology of hypoglossal nerve after crush injury.Our experimental findings indicate that exogenous nerve growth factor can protect damaged neurons and promote hypoglossal nerve regeneration following hypoglossal nerve crush injury.展开更多
Several studies have demonstrated that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats with diabetes mellitus. It is hypothesized that L-carnitine exhibits neuro-protective effects on inj...Several studies have demonstrated that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats with diabetes mellitus. It is hypothesized that L-carnitine exhibits neuro-protective effects on injured sciatic nerve of rats. Rat sciatic nerve was crush injured by a forceps and exhibited degenerative changes. After intragastric administration of 50 and 100 mg/kg L-carnitine for 30 days, axon area, myelin sheath area, axon diameter, myelin sheath diameter, and numerical density of the myelinated axons of injured sciatic nerve were similar to normal, and the function of injured sciatic nerve also improved signiifcantly. These ifndings suggest that L-carnitine exhibits neuroprotective effects on sciatic nerve crush injury in rats.展开更多
Neurotrophic factors,currently administered orally or by intravenous drip or intramuscular injection,are the main method for the treatment of peripheral nerve crush injury.However,the low effective drug concentration ...Neurotrophic factors,currently administered orally or by intravenous drip or intramuscular injection,are the main method for the treatment of peripheral nerve crush injury.However,the low effective drug concentration arriving at the injury site results in unsatisfactory outcomes.Therefore,there is an urgent need for a treatment method that can increase the effective drug concentration in the injured area.In this study,we first fabricated a gelatin modified by methacrylic anhydride hydrogel and loaded it with vascular endothelial growth factor that allowed the controlled release of the neurotrophic factor.This modified gelatin exhibited good physical and chemical properties,biocompatibility and supported the adhesion and proliferation of RSC96 cells and human umbilical vein endothelial cells.When injected into the epineurium of crushed nerves,the composite hydrogel in the rat sciatic nerve crush injury model promoted nerve regeneration,functional recovery and vascularization.The results showed that the modified gelatin gave sustained delivery of vascular endothelial growth factors and accelerated the repair of crushed peripheral nerves.展开更多
Several studies have shown that fibroblast growth factor-2 （FGF2） can directly affect axon regeneration after peripheral nerve damage. In this study, we performed sensory tests and histological analyses to study the...Several studies have shown that fibroblast growth factor-2 （FGF2） can directly affect axon regeneration after peripheral nerve damage. In this study, we performed sensory tests and histological analyses to study the effect of recombinant human FGF-2 （rhFGF2） treatment on damaged mental nerves. The mental nerves of 6-week-old male Sprague-Dawley rats were crush-injured for 1 minute and then treated with 10 or 50 μg/mL rhFGF2 or PBS in crush injury area with a mini Osmotic pump. Sensory test using von Frey filaments at 1 week revealed the presence of sensory degeneration based on decreased gap score and increased difference score. However, at 2 weeks, the gap score and difference score were significantly rebounded in the mental nerve crush group treated with 10 μg/mL rhFGF2. Interestingly, treatment with 10 μg/mL rhFGF had a more obviously positive effect on the gap score than treatment with 50 μg/mL rhFGF2. In addition, retrograde neuronal tracing with Dil revealed a significant increase in nerve regeneration in the trigeminal ganglion at 2 and 4 weeks in the rhFGF2 groups （10 μg/mL and 50 μg/mL） than in the PBS group. The 10 μg/mL rhFGF2 group also showed an obviously robust regeneration in axon density in the mental nerve at 4 weeks. Our results demonstrate that 10 μg/mL rhFGF induces mental nerve regeneration and sensory recovery after mental nerve crush injury.展开更多
Modern warfare has caused a large number of severe extremity injuries, many of which become infected. In more recent conflicts, a pattern of co-infection with Acinetobacter baumannii and methicillin-resistant Staphylo...Modern warfare has caused a large number of severe extremity injuries, many of which become infected. In more recent conflicts, a pattern of co-infection with Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus has emerged. We attempted to recreate this pattern in an animal model to evaluate the role of vascularity in contaminated open fractures. Historically, it has been observed that infected bones frequently appear hypovascular, but vascularity in association with bone infection has not been examined in animal models. Adult rats underwent femur fracture and muscle crush injury followed by stabilization and bacterial contamination with A. baumannii complex and methicillin-resistant Staphylococcus aureus.Vascularity and perfusion were assessed by micro CT angiography and SPECT scanning, respectively, at 1, 2 and 4 weeks after injury. Quantitative bacterial cultures were also obtained. Multi-bacterial infections were successfully created, with methicillin-resistant S. aureus predominating. There was overall increase in blood flow to injured limbs that was markedly greater in bacteria-inoculated limbs. Vessel volume was greater in the infected group. Quadriceps atrophy was seen in both groups, but was greater in the infected group. In this animal model, infected open fractures had greater perfusion and vascularity than non-infected limbs.展开更多
Nitric oxide(NO)has been shown to promote revascularization and nerve regeneration after peripheral nerve injury.However,in vivo application of NO remains challenging due to the lack of stable carrier materials capabl...Nitric oxide(NO)has been shown to promote revascularization and nerve regeneration after peripheral nerve injury.However,in vivo application of NO remains challenging due to the lack of stable carrier materials capable of storing large amounts of NO molecules and releasing them on a clinically meaningful time scale.Recently,a silica nanoparticle system capable of reversible NO storage and release at a controlled and sustained rate was introduced.In this study,NO-releasing silica nanoparticles(NO-SNs)were delivered to the peripheral nerves in rats after acute crush injury,mixed with natural hydrogel,to ensure the effective application of NO to the lesion.Microangiography using a polymer dye and immunohistochemical staining for the detection of CD34(a marker for revascularization)results showed that NO-releasing silica nanoparticles increased revascularization at the crush site of the sciatic nerve.The sciatic functional index revealed that there was a significant improvement in sciatic nerve function in NO-treated animals.Histological and anatomical analyses showed that the number of myelinated axons in the crushed sciatic nerve and wet muscle weight excised from NO-treated rats were increased.Moreover,muscle function recovery was improved in rats treated with NO-SNs.Taken together,our results suggest that NO delivered to the injured sciatic nerve triggers enhanced revascularization at the lesion in the early phase after crushing injury,thereby promoting axonal regeneration and improving functional recovery.展开更多
Background: Cytokines are essential cellular modulators of various physiological and pathological activities, including peripheral nerve repair and regeneration. However, the molecular changes of these cellular mediat...Background: Cytokines are essential cellular modulators of various physiological and pathological activities, including peripheral nerve repair and regeneration. However, the molecular changes of these cellular mediators after peripheral nerve injury are still unclear. This study aimed to identify cytokines critical for the regenerative process of injured peripheral nerves.Methods: The sequencing data of the injured nerve stumps and the dorsal root ganglia(DRG) of Sprague-Dawley(SD) rats subjected to sciatic nerve(SN) crush injury were analyzed to determine the expression patterns of genes coding for cytokines. PCR was used to validate the accuracy of the sequencing data.Results: A total of 46, 52, and 54 upstream cytokines were differentially expressed in the SN at 1 day, 4 days, and 7 days after nerve injury. A total of 25, 28, and 34 upstream cytokines were differentially expressed in the DRG at these time points. The expression patterns of some essential upstream cytokines are displayed in a heatmap and were validated by PCR. Bioinformatic analysis of these differentially expressed upstream cytokines after nerve injury demonstrated that inflammatory and immune responses were significantly involved.Conclusions: In summary, these findings provide an overview of the dynamic changes in cytokines in the SN and DRG at different time points after nerve crush injury in rats, elucidate the biological processes of differentially expressed cytokines, especially the important roles in inflammatory and immune responses after peripheral nerve injury, and thus might contribute to the identification of potential treatments for peripheral nerve repair and regeneration.展开更多
AIM: To investigate the features of abdominal crush injuries resulting from an earthquake using multidetector computed tomography (MDCT). METHODS: Fifty-one survivors with abdominal crush injuries due to the 2008 Sich...AIM: To investigate the features of abdominal crush injuries resulting from an earthquake using multidetector computed tomography (MDCT). METHODS: Fifty-one survivors with abdominal crush injuries due to the 2008 Sichuan earthquake underwent emergency non-enhanced scans with 16-row MDCT. Data were reviewed focusing on anatomic regions including lumbar vertebrae, abdominal wall soft tissue, retroperitoneum and intraperitoneal space; and types of traumatic lesions. RESULTS: Fractures of lumbar vertebrae and abdominal wall soft tissue injuries were more common than retro- and intraperitoneal injuries (P < 0.05). With regard to the 49 lumbar vertebral fractures in 24 patients, these occurred predominantly in the transverse process (P < 0.05), and 66.67% of patients (16/24) had fractures of multiple vertebrae, predominantly two vertebrae in 62.5% of patients (10/16), mainly in L1-3 vertebrae in 81.63% of the vertebrae (40/49). Retroperitoneal injuries occurred more frequently than intraperitoneal injuries (P < 0.05), and renal and liver injuries were most often seen in the retroperitoneum and in the intraperitoneal space, respectively (all P < 0.05). CONCLUSION: Transverse process fractures in two vertebrae among L1-3 vertebrae, injury of abdominal wall soft tissue, and renal injury might be features of earthquake-related crush abdominal injury.展开更多
Background On May 12, 2008, a major earthquake hit Wenchuan County in Sichuan Province of China. The number of cases of crush injury following this event was high. Ultrasonic appearance of rhabdomyolysis （RM） caused...Background On May 12, 2008, a major earthquake hit Wenchuan County in Sichuan Province of China. The number of cases of crush injury following this event was high. Ultrasonic appearance of rhabdomyolysis （RM） caused by crush injury in the Wenchuan earthquake was observed to evaluate the diagnostic value of ultrasound for detection of rhabdomyolysis. Methods We analyzed clinical and ultrasonic manifestations of 50 cases of RM and 18 cases of RM with osteofascial compartment syndrome （OCS）. All cases were caused by crush injury in the Wenchuan earthquake. For these RM patients, we also evaluated the correlations between creatine kinase （CK） and the scope of the muscle lesions as observed by ultrasound. Results There were differences in clinical symptoms, physical signs and ultrasonic appearance between the two groups of patients. The ultrasonic characteristics of the RM were as follows： the striated muscle in the lesions thickened with good overall continuity, and the muscle texture was vague; the strength of the echo was uneven and the echo was cloudy or ground glass-like. Liquid dark zones appeared between muscles and were spindle-like or irregular in shape. There were no blood flow signals in the liquid dark areas. The volume of the striated muscle increased in patients with OCS; the fascia wrapping the muscle showed arched protrusions and significant displacement. The flow velocity of the distal arteries decreased and the spectrum was abnormal. The muscle lesion scope of RM group and RM and OCS group was （7.8±2.0） cm and （13.6±3.1） cm, respectively. The correlation coefficient （r） between the muscle lesion scope and the CK was 0.681 for the RM group （P 〈0.05） and 0.516 for the RM and OCS group （P 〈0.05）. Conclusions The ultrasonogram of RM has characteristic manifestations and can provide important information for clinical diagnosis and treatment of rhabdomyolysis.展开更多
BACKGROUND Although the finger compartment syndrome is not common,it compresses the neurovascular bundles in a limited space and blocks blood flow to the fingers,causing necrosis of the fingertips.Finger fasciotomy th...BACKGROUND Although the finger compartment syndrome is not common,it compresses the neurovascular bundles in a limited space and blocks blood flow to the fingers,causing necrosis of the fingertips.Finger fasciotomy through unilateral or bilateral midline release of the finger can achieve decompression of the finger compartment.Herein,we report a case of the compartment syndrome in a finger injury caused by a high-pressure water flow which is commonly used in car washing stations.CASE SUMMARY A 60-year-old man injured his right middle finger while using a high-pressure washer at a car washing station.The patient complained of severe pain in his middle finger and a 0.2 cm punctured open wound on the volar side of the distal phalangeal joint of the middle finger.The fingertip was pale,numb,and characterized by severe swelling and a limited range of motion.Finger radiography showed that there was no fracture in the finger.Digital decompression was performed through finger fasciotomy by bilateral midline incision.On the second day after surgery,the color of the fingertip returned to pink,swelling was resolved,and the range of motion returned to normal.The sensation of the fingertip was completely restored,and the capillary refill test and pinprick test were positive.CONCLUSION The fingertip compartment syndrome can be caused by a high-pressure water flow damage to the fingers when using high-pressure washers at a car washing station.To avoid finger necrosis,rapid diagnosis of the finger compartment syndrome and appropriate digital decompression are essential to better outcome.展开更多
Studies have shown that acellular nerve xenografts do not require immunosuppression and use of acellular nerve xenografts for repair of peripheral nerve injury is safe and effective.However,there is currently no widel...Studies have shown that acellular nerve xenografts do not require immunosuppression and use of acellular nerve xenografts for repair of peripheral nerve injury is safe and effective.However,there is currently no widely accepted standard chemical decellularization method.The purpose of this study is to investigate the efficiency of bovine-derived nerves decellularized by the modified Hudson’s protocol in the repair of rat sciatic nerve injury.In the modified Hudson’s protocol,Triton X-200 was replaced by Triton X-100,and DNase and RNase were used to prepare accelular nerve xenografts.The efficiency of bovine-derived nerves decellularized by the modified Hudson’s protocol was tested in vitro by hematoxylin&eosin,Alcian blue,Masson’s trichrome,and Luxol fast blue staining,immunohistochemistry,and biochemical assays.The decellularization approach excluded cells,myelin,and axons of nerve xenografts,without affecting the organization of nerve xenografts.The decellularized nerve xenograft was used to bridge a 7 mm-long sciatic nerve defect to evaluate its efficiency in the repair of peripheral nerve injury.At 8 weeks after transplantation,sciatic function index in rats subjected to transplantation of acellular nerve xenograft was similar to that in rats undergoing transplantation of nerve allograft.Morphological analysis revealed that there were a large amount of regenerated myelinated axons in acellular nerve xenograft;the number of Schwann cells in the acellular nerve xenograft was similar to that in the nerve allograft.These findings suggest that acellular nerve xenografts prepared by the modified Hudson’s protocol can be used for repair of peripheral nerve injury.This study was approved by the Research Ethics Committee,Research and Technology Chancellor of Guilan University of Medical Sciences,Iran(approval No.IR.GUMS.REC.1395.332)on February 11,2017.展开更多
The regenerative capacity of peripheral nerves is limited after nerve injury.A number of growth factors modulate many cellular behaviors,such as proliferation and migration,and may contribute to nerve repair and regen...The regenerative capacity of peripheral nerves is limited after nerve injury.A number of growth factors modulate many cellular behaviors,such as proliferation and migration,and may contribute to nerve repair and regeneration.Our previous study observed the dynamic changes of genes in L4–6 dorsal root ganglion after rat sciatic nerve crush using transcriptome sequencing.Our current study focused on upstream growth factors and found that a total of 19 upstream growth factors were dysregulated in dorsal root ganglions at 3,9 hours,1,4,or 7 days after nerve crush,compared with the 0 hour control.Thirty-six rat models of sciatic nerve crush injury were prepared as described previously.Then,they were divided into six groups to measure the expression changes of representative genes at 0,3,9 hours,1,4 or 7 days post crush.Our current study measured the expression levels of representative upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin genes,and explored critical signaling pathways and biological process through bioinformatic analysis.Our data revealed that many of these dysregulated upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin,participated in tissue remodeling and axon growth-related biological processes Therefore,the experiment described the expression pattern of upstream growth factors in the dorsal root ganglia after peripheral nerve injury.Bioinformatic analysis revealed growth factors that may promote repair and regeneration of damaged peripheral nerves.All animal surgery procedures were performed in accordance with Institutional Animal Care Guidelines of Nantong University and ethically approved by the Administration Committee of Experimental Animals,China(approval No.20170302-017)on March 2,2017.展开更多
Several studies have demonstrated that human umbilical cord blood-derived mesenchymal stem cells can promote neural regeneration following brain injury. However, the therapeutic effects of human umbilical cord blood-d...Several studies have demonstrated that human umbilical cord blood-derived mesenchymal stem cells can promote neural regeneration following brain injury. However, the therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells in guiding peripheral nerve regeneration remain poorly understood. This study was designed to investigate the effects of human umbilical cord blood-derived mesenchymal stem cells on neural regeneration using a rat sciatic nerve crush injury model. Human umbilical cord blood-derived mesenchymal stem cells （1 ~ 106） or a PBS control were injected into the crush-injured segment of the sciatic nerve. Four weeks after cell injection, brain-derived neurotrophic factor and tyrosine kinase receptor B mRNA expression at the lesion site was increased in comparison to control. Furthermore, sciatic function index, Fluoro Gold-labeled neuron counts and axon density were also significantly increased when compared with control. Our results indicate that human umbilical cord blood-derived mesenchvmal stem cells promote the functinnal r~.RcJv^rv nf P.n I^h-inillr^4 ~r^i~tit, n^r~e展开更多
Both intracellular sigma peptide(ISP) and phosphatase and tensin homolog agonist protein(PAP4) promote nerve regeneration and motor functional recovery after spinal cord injury. However, the role of these two small pe...Both intracellular sigma peptide(ISP) and phosphatase and tensin homolog agonist protein(PAP4) promote nerve regeneration and motor functional recovery after spinal cord injury. However, the role of these two small peptides in peripheral nerve injury remains unclear. A rat model of brachial plexus injury was established by crush of the C6 ventral root. The rats were then treated with subcutaneous injection of PAP4(497 μg/d, twice per day) or ISP(11 μg/d, once per day) near the injury site for 21 successive days. After ISP and PAP treatment, the survival of motoneurons was increased, the number of regenerated axons and neuromuscular junctions was increased, muscle atrophy was reduced, the electrical response of the motor units was enhanced and the motor function of the injured upper limbs was greatly improved in rats with brachial plexus injury. These findings suggest that ISP and PAP4 promote the recovery of motor function after peripheral nerve injury in rats. The animal care and experimental procedures were approved by the Laboratory Animal Ethics Committee of Jinan University of China(approval No. 20111008001) in 2011.展开更多
BACKGROUND The February 6,2023,twin earthquakes in Türkiye caused significant structural damage and a high number of injuries,particularly affecting the spine,which underscores the importance of understanding the...BACKGROUND The February 6,2023,twin earthquakes in Türkiye caused significant structural damage and a high number of injuries,particularly affecting the spine,which underscores the importance of understanding the distribution and nature of vertebral injuries in disaster victims.AIM To investigate the distribution of radiological findings of vertebral injuries in patients referred to a major tertiary center during the February 6,2023 twin earthquakes in Türkiye.METHODS With the approval of the institutional ethics committee,1216 examinations of 238 patients transferred from the region to a tertiary major hospital after the twin earthquakes of February 6,2023,were retrospectively analyzed for spine injuries.RESULTS Spine computed tomography(CT)scans were performed in 192 of 238 patients with a suspected spinal injury,42 of whom also had an magnetic resonance imaging(MRI).In 86 of 192 patients(44.79%;M:F=33:53)a spinal fracture was detected on CT and in 33 of 42 patients(78.57%;M:F=20:13)a spinal injury was found on MRI.Of the 86 patients in whom vertebral injury was detected,fractures were detected in the Denis-B group in 33,Denis-C in 4,Denis-D in 20 and Denis-E in 11 patients.Among the vertebral bodies:40"compression fractures",17"burst fractures",5"translational dislocation fractures",5"flexion-distraction fractures"and 58"prolonged forced fetal posture fractures"were detected.In addition,isolated transverse or spinous process fractures were found in eighteen vertebrae.CONCLUSION Our study highlights the prevalence and diverse spectrum of spinal injuries following the February 6,2023 twin earthquakes in Turkey underscoring the urgent need for effective management strategies in similar disaster scenarios,and emphasizing the"prolonged forced fetal posture"damage we encountered in earthquake victims who remained under the collapse for a long time.展开更多
The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whe...The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.展开更多
Frankincense can promote blood circulation. Acetyl-11-keto-β-boswellic acid （AKBA） is a small molecule with anti-inflammatory properties that is derived from Boswellia serrata. Here, we hypothesized that it may pro...Frankincense can promote blood circulation. Acetyl-11-keto-β-boswellic acid （AKBA） is a small molecule with anti-inflammatory properties that is derived from Boswellia serrata. Here, we hypothesized that it may promote regeneration of injured sciatic nerve. To address this hypothesis, we established a rat model of sciatic nerve injury using a nerve clamping method. Rats were administered AKBA once every 2 days at doses of 1.5, 3, and 6 mg/kg by intraperitoneal injection for 30 days from the 1st day after injury. Sciatic nerve function was evaluated using the sciatic functional index. Degree of muscle atrophy was measured using the triceps surae muscle Cuadros index.Neuropathological changes were observed by hematoxylin-eosin staining. Western blot analysis was used to detect expression of phospho-extracellular signal-regulated kinase 1 and 2 （p-ERK1/2） in injured nerve. S100 immunoreactivity in injured nerve was detected by immunohistochemistry. In vivo experiments showed that 3 and 6 mg/kg AKBA significantly increased sciatic nerve index, Cuadros index of triceps muscle, p-ERK1/2 expression, and S100 immunoreactivity in injured sciatic nerve of sciatic nerve injury model rats. Furthermore,for in vitro experiments, Schwann cells were treated with AKBA at 0–20 μg/mL. Proliferation of Schwann cells was detected by Cell Counting Kit-8 colorimetry assay. The results showed that 2 μg/mL AKBA is the optimal therapeutic concentration. In addition, ERK phosphorylation levels increased following 2 μg/mL AKBA treatment. In the presence of the ERK1/2 inhibitor, PD98059 （2.5 μL/mL）, the AKBA-induced increase in p-ERK1/2 protein expression was partially abrogated. In conclusion, our study shows that AKBA promotes peripheral nerve regeneration with ERK protein phosphorylation playing a key role in this process.展开更多
基金supported by a grant from National Key Basic Research Program of China(973 Program),No.2014CB542202a grant from Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)in China
文摘We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To identify the major active component of ABPP, and thus optimize the use of ABPP, we used reverse-phase high performance liquid chromatography to separate ABPP. We obtained 12 fractions, among which the fraction of ABPPk demonstrated the strongest neuroactivity. Immunocytochemistry and western blot analysis showed that ABPPk promoted neurite growth in cultured dorsal root ganglion explant and dorsal root ganglion neurons, which might be associated with activation of Erk1/2. A combination of behavioral tests, electrophysiological assessment, and histomorphometric analysis indicated that ABPPk enhanced nerve regeneration and function restoration in a mouse model of crushed sciatic nerve. All the results suggest that ABPPk, as the key component of ABPP, can be used for peripheral nerve repair to yield better outcomes than ABPP.
文摘Studies have shown that sensory nerve damage can activate the p38 mitogen-activated protein kinase（MAPK）pathway,but whether the same type of nerve injury after exercise activates the p38MAPK pathway remains unclear.Several studies have demonstrated that nerve growth factor may play a role in the repair process after peripheral nerve injury,but there has been little research focusing on the hypoglossal nerve injury and repair.In this study,we designed and established rat models of hypoglossal nerve crush injury and gave intraperitoneal injections of exogenous nerve growth factor to rats for 14 days.p38MAPK activity in the damaged neurons was increased following hypoglossal nerve crush injury;exogenous nerve growth factor inhibited this increase in acitivity and increased the survival rate of motor neurons within the hypoglossal nucleus.Under transmission electron microscopy,we found that the injection of nerve growth factor contributed to the restoration of the morphology of hypoglossal nerve after crush injury.Our experimental findings indicate that exogenous nerve growth factor can protect damaged neurons and promote hypoglossal nerve regeneration following hypoglossal nerve crush injury.
基金supported by a grant from Ataturk University Scientific Experimental Project Office to Project Number 2012/07
文摘Several studies have demonstrated that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats with diabetes mellitus. It is hypothesized that L-carnitine exhibits neuro-protective effects on injured sciatic nerve of rats. Rat sciatic nerve was crush injured by a forceps and exhibited degenerative changes. After intragastric administration of 50 and 100 mg/kg L-carnitine for 30 days, axon area, myelin sheath area, axon diameter, myelin sheath diameter, and numerical density of the myelinated axons of injured sciatic nerve were similar to normal, and the function of injured sciatic nerve also improved signiifcantly. These ifndings suggest that L-carnitine exhibits neuroprotective effects on sciatic nerve crush injury in rats.
基金supported by the Interdisciplinary Program of Shanghai Jiao Tong University,China,No.YG2021QN60(both to WL)Fundamental Research Program Funding of Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,China,No.JYZZ086B(both to WL).
文摘Neurotrophic factors,currently administered orally or by intravenous drip or intramuscular injection,are the main method for the treatment of peripheral nerve crush injury.However,the low effective drug concentration arriving at the injury site results in unsatisfactory outcomes.Therefore,there is an urgent need for a treatment method that can increase the effective drug concentration in the injured area.In this study,we first fabricated a gelatin modified by methacrylic anhydride hydrogel and loaded it with vascular endothelial growth factor that allowed the controlled release of the neurotrophic factor.This modified gelatin exhibited good physical and chemical properties,biocompatibility and supported the adhesion and proliferation of RSC96 cells and human umbilical vein endothelial cells.When injected into the epineurium of crushed nerves,the composite hydrogel in the rat sciatic nerve crush injury model promoted nerve regeneration,functional recovery and vascularization.The results showed that the modified gelatin gave sustained delivery of vascular endothelial growth factors and accelerated the repair of crushed peripheral nerves.
基金supported by a grant from the Korea Healthcare Technology R&D Project,Ministry for Health,Welfare&Family Affairs,Republic of Korea,No.A101578
文摘Several studies have shown that fibroblast growth factor-2 （FGF2） can directly affect axon regeneration after peripheral nerve damage. In this study, we performed sensory tests and histological analyses to study the effect of recombinant human FGF-2 （rhFGF2） treatment on damaged mental nerves. The mental nerves of 6-week-old male Sprague-Dawley rats were crush-injured for 1 minute and then treated with 10 or 50 μg/mL rhFGF2 or PBS in crush injury area with a mini Osmotic pump. Sensory test using von Frey filaments at 1 week revealed the presence of sensory degeneration based on decreased gap score and increased difference score. However, at 2 weeks, the gap score and difference score were significantly rebounded in the mental nerve crush group treated with 10 μg/mL rhFGF2. Interestingly, treatment with 10 μg/mL rhFGF had a more obviously positive effect on the gap score than treatment with 50 μg/mL rhFGF2. In addition, retrograde neuronal tracing with Dil revealed a significant increase in nerve regeneration in the trigeminal ganglion at 2 and 4 weeks in the rhFGF2 groups （10 μg/mL and 50 μg/mL） than in the PBS group. The 10 μg/mL rhFGF2 group also showed an obviously robust regeneration in axon density in the mental nerve at 4 weeks. Our results demonstrate that 10 μg/mL rhFGF induces mental nerve regeneration and sensory recovery after mental nerve crush injury.
基金Department of Defense,Congressionally Directed Medical Research Program OR 090206 to SG.The Small Animal Phenotyping Core provided faxiotron and micro CT imaging (P30DK056336 and P30DK079626)
文摘Modern warfare has caused a large number of severe extremity injuries, many of which become infected. In more recent conflicts, a pattern of co-infection with Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus has emerged. We attempted to recreate this pattern in an animal model to evaluate the role of vascularity in contaminated open fractures. Historically, it has been observed that infected bones frequently appear hypovascular, but vascularity in association with bone infection has not been examined in animal models. Adult rats underwent femur fracture and muscle crush injury followed by stabilization and bacterial contamination with A. baumannii complex and methicillin-resistant Staphylococcus aureus.Vascularity and perfusion were assessed by micro CT angiography and SPECT scanning, respectively, at 1, 2 and 4 weeks after injury. Quantitative bacterial cultures were also obtained. Multi-bacterial infections were successfully created, with methicillin-resistant S. aureus predominating. There was overall increase in blood flow to injured limbs that was markedly greater in bacteria-inoculated limbs. Vessel volume was greater in the infected group. Quadriceps atrophy was seen in both groups, but was greater in the infected group. In this animal model, infected open fractures had greater perfusion and vascularity than non-infected limbs.
基金supported by the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT,Nos.NRF-2015R1C1A1A02036830(to JIL)and NRF-2015M3A9E2029186(to JHS)+1 种基金supported by a grant of the Korea Institute of Science and Technology,Nos.2V05460/2V08630(KIST-KU TRC program),2E31121(to MRO)a grant of Korea University Anam Hospital(to JHP and JWP).
文摘Nitric oxide(NO)has been shown to promote revascularization and nerve regeneration after peripheral nerve injury.However,in vivo application of NO remains challenging due to the lack of stable carrier materials capable of storing large amounts of NO molecules and releasing them on a clinically meaningful time scale.Recently,a silica nanoparticle system capable of reversible NO storage and release at a controlled and sustained rate was introduced.In this study,NO-releasing silica nanoparticles(NO-SNs)were delivered to the peripheral nerves in rats after acute crush injury,mixed with natural hydrogel,to ensure the effective application of NO to the lesion.Microangiography using a polymer dye and immunohistochemical staining for the detection of CD34(a marker for revascularization)results showed that NO-releasing silica nanoparticles increased revascularization at the crush site of the sciatic nerve.The sciatic functional index revealed that there was a significant improvement in sciatic nerve function in NO-treated animals.Histological and anatomical analyses showed that the number of myelinated axons in the crushed sciatic nerve and wet muscle weight excised from NO-treated rats were increased.Moreover,muscle function recovery was improved in rats treated with NO-SNs.Taken together,our results suggest that NO delivered to the injured sciatic nerve triggers enhanced revascularization at the lesion in the early phase after crushing injury,thereby promoting axonal regeneration and improving functional recovery.
基金supported by the Postgraduate Research&Practice Innovation Program of Jiangsu Province (KYCX19_2064)the Nantong University Undergraduate Innovation Program (201910304032Z)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)。
文摘Background: Cytokines are essential cellular modulators of various physiological and pathological activities, including peripheral nerve repair and regeneration. However, the molecular changes of these cellular mediators after peripheral nerve injury are still unclear. This study aimed to identify cytokines critical for the regenerative process of injured peripheral nerves.Methods: The sequencing data of the injured nerve stumps and the dorsal root ganglia(DRG) of Sprague-Dawley(SD) rats subjected to sciatic nerve(SN) crush injury were analyzed to determine the expression patterns of genes coding for cytokines. PCR was used to validate the accuracy of the sequencing data.Results: A total of 46, 52, and 54 upstream cytokines were differentially expressed in the SN at 1 day, 4 days, and 7 days after nerve injury. A total of 25, 28, and 34 upstream cytokines were differentially expressed in the DRG at these time points. The expression patterns of some essential upstream cytokines are displayed in a heatmap and were validated by PCR. Bioinformatic analysis of these differentially expressed upstream cytokines after nerve injury demonstrated that inflammatory and immune responses were significantly involved.Conclusions: In summary, these findings provide an overview of the dynamic changes in cytokines in the SN and DRG at different time points after nerve crush injury in rats, elucidate the biological processes of differentially expressed cytokines, especially the important roles in inflammatory and immune responses after peripheral nerve injury, and thus might contribute to the identification of potential treatments for peripheral nerve repair and regeneration.
基金Supported by The National Natural Science Foundation of China,No.30870688The Science Foundation for Distinguished Young Scholars of Sichuan Province,No.2010JQ0039
文摘AIM: To investigate the features of abdominal crush injuries resulting from an earthquake using multidetector computed tomography (MDCT). METHODS: Fifty-one survivors with abdominal crush injuries due to the 2008 Sichuan earthquake underwent emergency non-enhanced scans with 16-row MDCT. Data were reviewed focusing on anatomic regions including lumbar vertebrae, abdominal wall soft tissue, retroperitoneum and intraperitoneal space; and types of traumatic lesions. RESULTS: Fractures of lumbar vertebrae and abdominal wall soft tissue injuries were more common than retro- and intraperitoneal injuries (P < 0.05). With regard to the 49 lumbar vertebral fractures in 24 patients, these occurred predominantly in the transverse process (P < 0.05), and 66.67% of patients (16/24) had fractures of multiple vertebrae, predominantly two vertebrae in 62.5% of patients (10/16), mainly in L1-3 vertebrae in 81.63% of the vertebrae (40/49). Retroperitoneal injuries occurred more frequently than intraperitoneal injuries (P < 0.05), and renal and liver injuries were most often seen in the retroperitoneum and in the intraperitoneal space, respectively (all P < 0.05). CONCLUSION: Transverse process fractures in two vertebrae among L1-3 vertebrae, injury of abdominal wall soft tissue, and renal injury might be features of earthquake-related crush abdominal injury.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30801067）.
文摘Background On May 12, 2008, a major earthquake hit Wenchuan County in Sichuan Province of China. The number of cases of crush injury following this event was high. Ultrasonic appearance of rhabdomyolysis （RM） caused by crush injury in the Wenchuan earthquake was observed to evaluate the diagnostic value of ultrasound for detection of rhabdomyolysis. Methods We analyzed clinical and ultrasonic manifestations of 50 cases of RM and 18 cases of RM with osteofascial compartment syndrome （OCS）. All cases were caused by crush injury in the Wenchuan earthquake. For these RM patients, we also evaluated the correlations between creatine kinase （CK） and the scope of the muscle lesions as observed by ultrasound. Results There were differences in clinical symptoms, physical signs and ultrasonic appearance between the two groups of patients. The ultrasonic characteristics of the RM were as follows： the striated muscle in the lesions thickened with good overall continuity, and the muscle texture was vague; the strength of the echo was uneven and the echo was cloudy or ground glass-like. Liquid dark zones appeared between muscles and were spindle-like or irregular in shape. There were no blood flow signals in the liquid dark areas. The volume of the striated muscle increased in patients with OCS; the fascia wrapping the muscle showed arched protrusions and significant displacement. The flow velocity of the distal arteries decreased and the spectrum was abnormal. The muscle lesion scope of RM group and RM and OCS group was （7.8±2.0） cm and （13.6±3.1） cm, respectively. The correlation coefficient （r） between the muscle lesion scope and the CK was 0.681 for the RM group （P 〈0.05） and 0.516 for the RM and OCS group （P 〈0.05）. Conclusions The ultrasonogram of RM has characteristic manifestations and can provide important information for clinical diagnosis and treatment of rhabdomyolysis.
文摘BACKGROUND Although the finger compartment syndrome is not common,it compresses the neurovascular bundles in a limited space and blocks blood flow to the fingers,causing necrosis of the fingertips.Finger fasciotomy through unilateral or bilateral midline release of the finger can achieve decompression of the finger compartment.Herein,we report a case of the compartment syndrome in a finger injury caused by a high-pressure water flow which is commonly used in car washing stations.CASE SUMMARY A 60-year-old man injured his right middle finger while using a high-pressure washer at a car washing station.The patient complained of severe pain in his middle finger and a 0.2 cm punctured open wound on the volar side of the distal phalangeal joint of the middle finger.The fingertip was pale,numb,and characterized by severe swelling and a limited range of motion.Finger radiography showed that there was no fracture in the finger.Digital decompression was performed through finger fasciotomy by bilateral midline incision.On the second day after surgery,the color of the fingertip returned to pink,swelling was resolved,and the range of motion returned to normal.The sensation of the fingertip was completely restored,and the capillary refill test and pinprick test were positive.CONCLUSION The fingertip compartment syndrome can be caused by a high-pressure water flow damage to the fingers when using high-pressure washers at a car washing station.To avoid finger necrosis,rapid diagnosis of the finger compartment syndrome and appropriate digital decompression are essential to better outcome.
基金supported by the Research and Technology Chancellor of Guilan University of Medical Sciences(No.95110202to AZa).
文摘Studies have shown that acellular nerve xenografts do not require immunosuppression and use of acellular nerve xenografts for repair of peripheral nerve injury is safe and effective.However,there is currently no widely accepted standard chemical decellularization method.The purpose of this study is to investigate the efficiency of bovine-derived nerves decellularized by the modified Hudson’s protocol in the repair of rat sciatic nerve injury.In the modified Hudson’s protocol,Triton X-200 was replaced by Triton X-100,and DNase and RNase were used to prepare accelular nerve xenografts.The efficiency of bovine-derived nerves decellularized by the modified Hudson’s protocol was tested in vitro by hematoxylin&eosin,Alcian blue,Masson’s trichrome,and Luxol fast blue staining,immunohistochemistry,and biochemical assays.The decellularization approach excluded cells,myelin,and axons of nerve xenografts,without affecting the organization of nerve xenografts.The decellularized nerve xenograft was used to bridge a 7 mm-long sciatic nerve defect to evaluate its efficiency in the repair of peripheral nerve injury.At 8 weeks after transplantation,sciatic function index in rats subjected to transplantation of acellular nerve xenograft was similar to that in rats undergoing transplantation of nerve allograft.Morphological analysis revealed that there were a large amount of regenerated myelinated axons in acellular nerve xenograft;the number of Schwann cells in the acellular nerve xenograft was similar to that in the nerve allograft.These findings suggest that acellular nerve xenografts prepared by the modified Hudson’s protocol can be used for repair of peripheral nerve injury.This study was approved by the Research Ethics Committee,Research and Technology Chancellor of Guilan University of Medical Sciences,Iran(approval No.IR.GUMS.REC.1395.332)on February 11,2017.
基金supported by the Natural Science Foundation of Jiangsu Higher Education Institutions of China(Major Program),No.16KJA310005(to SYL)the Natural Science Foundation of Nantong City of China,No.JC2018058(to TMQ)the Priority Academic Program Development of Jiangsu Higher Education Institutions of China
文摘The regenerative capacity of peripheral nerves is limited after nerve injury.A number of growth factors modulate many cellular behaviors,such as proliferation and migration,and may contribute to nerve repair and regeneration.Our previous study observed the dynamic changes of genes in L4–6 dorsal root ganglion after rat sciatic nerve crush using transcriptome sequencing.Our current study focused on upstream growth factors and found that a total of 19 upstream growth factors were dysregulated in dorsal root ganglions at 3,9 hours,1,4,or 7 days after nerve crush,compared with the 0 hour control.Thirty-six rat models of sciatic nerve crush injury were prepared as described previously.Then,they were divided into six groups to measure the expression changes of representative genes at 0,3,9 hours,1,4 or 7 days post crush.Our current study measured the expression levels of representative upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin genes,and explored critical signaling pathways and biological process through bioinformatic analysis.Our data revealed that many of these dysregulated upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin,participated in tissue remodeling and axon growth-related biological processes Therefore,the experiment described the expression pattern of upstream growth factors in the dorsal root ganglia after peripheral nerve injury.Bioinformatic analysis revealed growth factors that may promote repair and regeneration of damaged peripheral nerves.All animal surgery procedures were performed in accordance with Institutional Animal Care Guidelines of Nantong University and ethically approved by the Administration Committee of Experimental Animals,China(approval No.20170302-017)on March 2,2017.
基金supported by a grant of the Seoul National University Dental Hospital,Republic of Korea,No.03-2010-0020
文摘Several studies have demonstrated that human umbilical cord blood-derived mesenchymal stem cells can promote neural regeneration following brain injury. However, the therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells in guiding peripheral nerve regeneration remain poorly understood. This study was designed to investigate the effects of human umbilical cord blood-derived mesenchymal stem cells on neural regeneration using a rat sciatic nerve crush injury model. Human umbilical cord blood-derived mesenchymal stem cells （1 ~ 106） or a PBS control were injected into the crush-injured segment of the sciatic nerve. Four weeks after cell injection, brain-derived neurotrophic factor and tyrosine kinase receptor B mRNA expression at the lesion site was increased in comparison to control. Furthermore, sciatic function index, Fluoro Gold-labeled neuron counts and axon density were also significantly increased when compared with control. Our results indicate that human umbilical cord blood-derived mesenchvmal stem cells promote the functinnal r~.RcJv^rv nf P.n I^h-inillr^4 ~r^i~tit, n^r~e
基金supported by the National Natural Science Foundation of China,No. 81971165the National Basic Research Program of China (973 Program),No. 2014CB542205 (both to WW)。
文摘Both intracellular sigma peptide(ISP) and phosphatase and tensin homolog agonist protein(PAP4) promote nerve regeneration and motor functional recovery after spinal cord injury. However, the role of these two small peptides in peripheral nerve injury remains unclear. A rat model of brachial plexus injury was established by crush of the C6 ventral root. The rats were then treated with subcutaneous injection of PAP4(497 μg/d, twice per day) or ISP(11 μg/d, once per day) near the injury site for 21 successive days. After ISP and PAP treatment, the survival of motoneurons was increased, the number of regenerated axons and neuromuscular junctions was increased, muscle atrophy was reduced, the electrical response of the motor units was enhanced and the motor function of the injured upper limbs was greatly improved in rats with brachial plexus injury. These findings suggest that ISP and PAP4 promote the recovery of motor function after peripheral nerve injury in rats. The animal care and experimental procedures were approved by the Laboratory Animal Ethics Committee of Jinan University of China(approval No. 20111008001) in 2011.
基金the guidelines of the Declaration of Helsinki and approval for this retrospective study was obtained from the Institutional Ethics Board(SBA 24/077).
文摘BACKGROUND The February 6,2023,twin earthquakes in Türkiye caused significant structural damage and a high number of injuries,particularly affecting the spine,which underscores the importance of understanding the distribution and nature of vertebral injuries in disaster victims.AIM To investigate the distribution of radiological findings of vertebral injuries in patients referred to a major tertiary center during the February 6,2023 twin earthquakes in Türkiye.METHODS With the approval of the institutional ethics committee,1216 examinations of 238 patients transferred from the region to a tertiary major hospital after the twin earthquakes of February 6,2023,were retrospectively analyzed for spine injuries.RESULTS Spine computed tomography(CT)scans were performed in 192 of 238 patients with a suspected spinal injury,42 of whom also had an magnetic resonance imaging(MRI).In 86 of 192 patients(44.79%;M:F=33:53)a spinal fracture was detected on CT and in 33 of 42 patients(78.57%;M:F=20:13)a spinal injury was found on MRI.Of the 86 patients in whom vertebral injury was detected,fractures were detected in the Denis-B group in 33,Denis-C in 4,Denis-D in 20 and Denis-E in 11 patients.Among the vertebral bodies:40"compression fractures",17"burst fractures",5"translational dislocation fractures",5"flexion-distraction fractures"and 58"prolonged forced fetal posture fractures"were detected.In addition,isolated transverse or spinous process fractures were found in eighteen vertebrae.CONCLUSION Our study highlights the prevalence and diverse spectrum of spinal injuries following the February 6,2023 twin earthquakes in Turkey underscoring the urgent need for effective management strategies in similar disaster scenarios,and emphasizing the"prolonged forced fetal posture"damage we encountered in earthquake victims who remained under the collapse for a long time.
基金supported by the National Natural Science Foundation of China,No.81171178the Natural Science Foundation of Shanxi Province in China,No.2012011036-3Scientific Research Foundation of Shanxi Province of China for the Returned Overseas Chinese Scholars,No.2013011054-2
文摘The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.
文摘Frankincense can promote blood circulation. Acetyl-11-keto-β-boswellic acid （AKBA） is a small molecule with anti-inflammatory properties that is derived from Boswellia serrata. Here, we hypothesized that it may promote regeneration of injured sciatic nerve. To address this hypothesis, we established a rat model of sciatic nerve injury using a nerve clamping method. Rats were administered AKBA once every 2 days at doses of 1.5, 3, and 6 mg/kg by intraperitoneal injection for 30 days from the 1st day after injury. Sciatic nerve function was evaluated using the sciatic functional index. Degree of muscle atrophy was measured using the triceps surae muscle Cuadros index.Neuropathological changes were observed by hematoxylin-eosin staining. Western blot analysis was used to detect expression of phospho-extracellular signal-regulated kinase 1 and 2 （p-ERK1/2） in injured nerve. S100 immunoreactivity in injured nerve was detected by immunohistochemistry. In vivo experiments showed that 3 and 6 mg/kg AKBA significantly increased sciatic nerve index, Cuadros index of triceps muscle, p-ERK1/2 expression, and S100 immunoreactivity in injured sciatic nerve of sciatic nerve injury model rats. Furthermore,for in vitro experiments, Schwann cells were treated with AKBA at 0–20 μg/mL. Proliferation of Schwann cells was detected by Cell Counting Kit-8 colorimetry assay. The results showed that 2 μg/mL AKBA is the optimal therapeutic concentration. In addition, ERK phosphorylation levels increased following 2 μg/mL AKBA treatment. In the presence of the ERK1/2 inhibitor, PD98059 （2.5 μL/mL）, the AKBA-induced increase in p-ERK1/2 protein expression was partially abrogated. In conclusion, our study shows that AKBA promotes peripheral nerve regeneration with ERK protein phosphorylation playing a key role in this process.
