Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving mul...Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving multifaceted cellular and molecular processes.The contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large gap.Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI.The recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.展开更多
The effect of platelet-rich plasma on nerve regeneration remains controversial.In this study,we established a rabbit model of sciatic nerve small-gap defects with preserved epineurium and then filled the gaps with pla...The effect of platelet-rich plasma on nerve regeneration remains controversial.In this study,we established a rabbit model of sciatic nerve small-gap defects with preserved epineurium and then filled the gaps with platelet-rich plasma.Twenty-eight rabbits were divided into the following groups(7 rabbits/group):model,low-concentrati on PRP(2.5-3.5-fold concentration of whole blood platelets),medium-concentration PRP(4.5-6.5-fold concentration of whole blood platelets),and high-concentration PRP(7.5-8.5-fold concentration of whole blood platelets).Electrophysiological and histomorphometrical assessments and proteomics analysis we re used to evaluate regeneration of the sciatic nerve.Our results showed that platelet-rich plasma containing 4.5-6.5-and 7.5-8.5-fold concentrations of whole blood platelets promoted repair of sciatic nerve injury.Proteomics analysis was performed to investigate the possible mechanism by which platelet-rich plasma promoted nerve regeneration.Proteomics analysis showed that after sciatic nerve injury,platelet-rich plasma increased the expression of integrin subunitβ-8(ITGB8),which participates in angiogenesis,and differentially expressed proteins were mainly enriched in focal adhesion pathways.Additionally,two key proteins,ribosomal protein S27 a(RSP27 a)and ubiquilin 1(UBQLN1),which were selected after protein-protein interaction analysis,are involved in the regulation of ubiquitin levels in vivo.These data suggest that platelet-rich plasma promotes peripheral nerve regeneration after sciatic nerve injury by affecting angiogenesis and intracellular ubiquitin levels.展开更多
Background:The underlying mechanism of sciatic nerve injury(SNI)is a common motor functional disorder,necessitates further research.Methods:A rat model of SNI was established,with the injury group subjected to compres...Background:The underlying mechanism of sciatic nerve injury(SNI)is a common motor functional disorder,necessitates further research.Methods:A rat model of SNI was established,with the injury group subjected to compressive injury of the right sciatic nerve exposed at the midpoint of the thigh and the sham surgery group undergoing the same surgical procedure.An oxygen-glucose deprivation model was employed to simulate in vitro SNI in PC12 cells.Following data acquisition and quality control,differentially expressed proteins(DEPs)in each model were identified through differential analysis,and enrichment analysis was used to explore the potential functions and pathways of the DEPs.Venn diagrams were drawn,and DEPs from both in vivo and in vitro SNI models were imported into the STRING database to construct a protein-protein interaction network and screen for hub proteins.Results:After the peptide segments obtained from rat nerve blockade and PC12 cells met quality requirements,258 DEPs were identified in rat nerve samples,and 119 DEPs were screened in PC12 cells.Enrichment analysis revealed that DEPs in the rat model were predominantly concentrated in biological functions such as myogenic cell proliferation and signaling related to lipid and energy metabolism.DEPs in the in vitro model were mainly enriched in biological processes such as phagocytosis and were associated with lipid transport and metabolism.Two hub proteins,amyloid precursor protein(APP)and fibronectin 1(FN1),were identified through MCC,MCODE,and Degree scoring.Both PC12 cells and external validation sets showed relatively higher expression of APP and FN1 in injured samples.Results of gene set enrichment analysis indicated that these two proteins were associated with metabolic pathways,such as biosynthesis of glycosaminoglycan chondroitin sulfate and biosynthesis of unsaturated fatty acids.Conclusion:APP and FN1 are potential key molecules involved in SNI and are associated with various metabolic pathways in nerve repair.These findings provide a theoretical basis for the development of therapeutic targets for SNI.展开更多
Monocytes,including monocyte-derived macrophages and resident microglia,mediate many phases of optic nerve injury pathogenesis.Resident microglia respond first,followed by infiltrating macrophages which regulate neuro...Monocytes,including monocyte-derived macrophages and resident microglia,mediate many phases of optic nerve injury pathogenesis.Resident microglia respond first,followed by infiltrating macrophages which regulate neuronal inflammation,cell proliferation and differentiation,scar formation and tissue remodeling following optic nerve injury.However,microglia and macrophages have distinct functions which can be either beneficial or detrimental to the optic nerve depending on the spatial context and temporal sequence of their activity.These divergent effects are attributed to pro-and anti-inflammatory cytokines expressed by monocytes,crosstalk between monocyte and glial cells and even microglia-macrophage communication.In this review,we describe the dynamics and functions of microglia and macrophages in neuronal inflammation and regeneration following optic nerve injury,and their possible role as therapeutic targets for axonal regeneration.展开更多
We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role...We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.展开更多
Research has shown that long-chain noncoding RNAs(lncRNAs) are involved in the regulation of a variety of biological processes, including peripheral nerve regeneration, in part by acting as competing endogenous RNAs. ...Research has shown that long-chain noncoding RNAs(lncRNAs) are involved in the regulation of a variety of biological processes, including peripheral nerve regeneration, in part by acting as competing endogenous RNAs. c-Jun plays a key role in the repair of peripheral nerve injury. However, the precise underlying mechanism of c-Jun remains unclear. In this study, we performed microarray and bioinformatics analysis of mouse crush-injured sciatic nerves and found that the lncRNA Pvt1 was overexpressed in Schwann cells after peripheral nerve injury. Mechanistic studies revealed that Pvt1 increased c-Jun expression through sponging miRNA-214. We overexpressed Pvt1 in Schwann cells cultured in vitro and found that the proliferation and migration of Schwann cells were enhanced, and overexpression of miRNA-214 counteracted the effects of Pvt1 overexpression on Schwann cell proliferation and migration. We conducted in vivo analyses and injected Schwann cells overexpressing Pvt1 into injured sciatic nerves of mice. Schwann cells overexpressing Pvt1 enhanced the regeneration of injured sciatic nerves following peripheral nerve injury and the locomotor function of mice was improved. Our findings reveal the role of lncRNAs in the repair of peripheral nerve injury and highlight lncRNA Pvt1 as a novel potential treatment target for peripheral nerve injury.展开更多
Epigenetic changes in the spinal cord play a key role in the initiation and maintenance of nerve injury-induced neuro pathic pain.N6-methyladenosine(m6A)is one of the most abundant internal RNA modifications and plays...Epigenetic changes in the spinal cord play a key role in the initiation and maintenance of nerve injury-induced neuro pathic pain.N6-methyladenosine(m6A)is one of the most abundant internal RNA modifications and plays an essential function in gene regulation in many diseases.However,the global m6A modification status of mRNA in the spinal cord at different stages after neuropathic pain is unknown.In this study,we established a neuropathic pain model in mice by preserving the complete sural nerve and only damaging the common peroneal nerve.High-throughput methylated RNA immunoprecipitation sequencing res ults showed that after spared nerve injury,there were 55 m6A methylated and diffe rentially expressed genes in the spinal cord.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway results showed that m6A modification triggered inflammatory responses and apoptotic processes in the early stages after spared nerve injury.Over time,the diffe rential gene function at postoperative day 7 was enriched in "positive regulation of neurogenesis" and "positive regulation of neural precursor cell prolife ration." These functions suggested that altered synaptic morphological plasticity was a turning point in neuropathic pain formation and maintenance.Results at postoperative day 14 suggested that the persistence of neuropathic pain might be from lipid metabolic processes,such as "very-low-density lipoprotein particle clearance," "negative regulation of choleste rol transport" and "membrane lipid catabolic process." We detected the expression of m6A enzymes and found elevated mRNA expression of Ythdf2 and Ythdf3 after spared nerve injury modeling.We speculate that m6A reader enzymes also have an important role in neuropathic pain.These results provide a global landscape of mRNA m6A modifications in the spinal cord in the spared nerve injury model at diffe rent stages after injury.展开更多
To determine the value of dissecting the recurrent laryngeal nerve during thyroid surgery with respect to preventing recurrent laryngeal nerve injury, we retrospectively analyzed clinical data from 5 344 patients unde...To determine the value of dissecting the recurrent laryngeal nerve during thyroid surgery with respect to preventing recurrent laryngeal nerve injury, we retrospectively analyzed clinical data from 5 344 patients undergoing thyroidectomy. Among these cases, 548 underwent dissection of the recurrent laryngeal nerve, while 4 796 did not. There were 12 cases of recurrent laryngeal nerve injury following recurrent laryngeal nerve dissection (injury rate of 2.2%) and 512 cases of recurrenl laryngeal nerve injury in those not undergoing nerve dissection (injury rate of 10.7%). This difference remained statistically significant between the two groups in terms of type of thyroid disease, type of surgery, and number of surgeries. Among the 548 cases undergoing recurrent laryngeal nerve dissection, 128 developed anatomical variations of the recurrent laryngeal nerve (incidence rate of 23.4%), but no recurrent laryngeal nerve injury was found. In addition, the incidence of recurrent laryngeal nerve injury was significantly lower in patients with the infedor parathyroid gland and middle thyroid veins used as landmarks for locating the recurrent laryngeal nerve compared with those with the entry of the recurrent laryngeal nerve into the larynx as a landmark. These findings indicate that anatomical variations of the recurrent laryngeal nerve are common, and that dissecting the recurrent laryngeal nerve during thyroid surgery is an effective means of preventing nerve injury.展开更多
Claudin 14 has been shown to promote nerve repair and regeneration in the early stages of Wallerian degeneration (0-4 days) in rats with sciatic nerve injury, but the mechanism underlying this process remains poorly...Claudin 14 has been shown to promote nerve repair and regeneration in the early stages of Wallerian degeneration (0-4 days) in rats with sciatic nerve injury, but the mechanism underlying this process remains poorly understood. This study reported the effects of claudin 14 on nerve degeneration and regeneration during early Wallerian degeneration. Claudin 14 expression was up-regulated in sciatic nerve 4 days after Wallerian degeneration. The altered expression of claudin 14 in Schwann cells resulted in expression changes of cytokines in vitro. Expression of claudin 14 affected c-Jun, but not Akt anal ERK1/2 patl^ways, l^urther studies reve^ed that enhanced expression of claudin 14 could promote Schwann cell proliferation and migration. Silencing of claudin 14 expression resulted in Schwann cell apoptosis and reduction in Schwann cell proliferation. Our data revealed the role of claudin 14 in early Wallerian degeneration, which may provide new insights into the molecular mechanisms of Wallerian degeneration.展开更多
Wallerian degeneration is a subject of major interest in neuroscience. A large number of genes are differentially regulated during the distinct stages of Wallerian degeneration: transcription factor activation, immun...Wallerian degeneration is a subject of major interest in neuroscience. A large number of genes are differentially regulated during the distinct stages of Wallerian degeneration: transcription factor activation, immune response, myelin cell differentiation and dedifferentiation. Although gene expression responses in the distal segment of the sciatic nerve after peripheral nerve injury are known, differences in gene expression between the proximal and distal segments remain unclear. In the present study in rats, we used microarrays to analyze changes in gene expression, biological processes and signaling pathways in the proximal and distal segments of sciatic nerves under- going Wallerian degeneration. More than 6,000 genes were differentially expressed and 20 types of expression tendencies were identified, mainly between proximal and distal segments at 7-14 days after injury. The differentially expressed genes were those involved in cell differentiation, cytokinesis, neuron differentiation, nerve development and axon regeneration. Furthermore, 11 biological processes were represented, related to responses to stimuli, cell apoptosis, inflammato- ry response, immune response, signal transduction, protein kinase activity, and cell proliferation. Using real-time quantitative PCR, western blot analysis and immunohistochemistry, microarray data were verified for four genes: aquaporin-4, interleukin 1 receptor-like 1, matrix metallopro- teinase-12 and periaxin. Our study identifies differential gene expression in the proximal and distal segments of a nerve during Wallerian degeneration, analyzes dynamic biological changes of these genes, and provides a useful platform for the detailed study of nerve injury and repair during Wallerian degeneration.展开更多
This study investigated the possible involvement of microRNAs in the regulation of genes that participate in peripheral neural regeneration. A microRNA microarray analysis was conducted and 23 microRNAs were identiife...This study investigated the possible involvement of microRNAs in the regulation of genes that participate in peripheral neural regeneration. A microRNA microarray analysis was conducted and 23 microRNAs were identiifed whose expression was signiifcantly changed in rat dorsal root ganglia after sciatic nerve transection. The expression of one of the downregulated microRNAs, microRNA-214, was validated using quantitative reverse transcriptase-PCR. MicroRNA-214 was predicted to target the 3′-untranslated region of Slit-Robo GTPase-activating protein 3. In situ hybridization veriifed that microRNA-214 was located in the cytoplasm of dorsal root ganglia primary neurons and was downregulated following sciatic nerve transection. Moreover, a com-bination of in situ hybridization and immunohistochemistry revealed that microRNA-214 and Slit-Robo GTPase-activating protein 3 were co-localized in dorsal root ganglion primary neu-rons. Western blot analysis suggested that Slit-Robo GTPase-activating protein 3 was upregulated in dorsal root ganglion neurons after sciatic nerve transection. These data demonstrate that mi-croRNA-214 is located and differentially expressed in dorsal root ganglion primary neurons and may participate in regulating the gene expression of Slit-Robo GTPase-activating protein 3 after sciatic nerve transection.展开更多
Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve injury. However, the therapeutic effect of edaravone on peripheral nerve injury caused by mechanical factors is unknown. In the present ...Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve injury. However, the therapeutic effect of edaravone on peripheral nerve injury caused by mechanical factors is unknown. In the present study, we established a peripheral nerve injury model by crushing the sciatic nerve using hemostatic forceps, and then administered edaravone 3 mg/kg intraperitoneally. The sciatic functional index and superoxide dismutase activity of the sciatic nerve were increased, and the malondialdehyde level was decreased in animals in the edaravone group compared with those in the model group. Bcl-2 expression was increased, but Bax expres- sion was decreased in anterior horn cells of the L4-6 spinal cord segments. These results indicated that edaravone has a neuroprotective effect following peripheral nerve injury caused by mechan- ical factors through alleviating free radical damage to cells and inhibiting lipid peroxidation, as well as regulating apoptosis-related protein expression.展开更多
The magnitude of tensile stress and tensile strain at an anastomosis site under physiological stress is an important factor for the success of anastomosis following suturing in peripheral nerve injury treatment. Sciat...The magnitude of tensile stress and tensile strain at an anastomosis site under physiological stress is an important factor for the success of anastomosis following suturing in peripheral nerve injury treatment. Sciatic nerves from fresh adult cadavers were used to create models of sciatic nerve injury. The denervated specimens underwent epineurial and perineurial suturing. The elastic modulus (40.96 + 2.59 MPa) and Poisson ratio (0.37 + 0.02) of the normal sciatic nerve were measured by strain electrical measurement. A resistance strain gauge was pasted on the front, back left, and right of the edge of the anastomosis site after suturing. Strain electrical measurement results showed that the stress and strain values of the sciatic nerve following perineurial suturing were lower than those following epineurial suturing. Scanning electron microscopy revealed that the sciatic nerve fibers were disordered following epineurial compared with perineurial suturing. These results indicate that the effect of perineurial suturing in sciatic nerve injury repair is better than that of epineurial suturing.展开更多
Peripheral nerve injury may trigger changes in mRNA levels in the spinal cord.Finding key mRNAs is important for improving repair after nerve injury.This study aimed to investigate changes in mRNAs in the spinal cord ...Peripheral nerve injury may trigger changes in mRNA levels in the spinal cord.Finding key mRNAs is important for improving repair after nerve injury.This study aimed to investigate changes in mRNAs in the spinal cord following sciatic nerve injury by transcriptomic analysis.The left sciatic nerve denervation model was established in C57 BL/6 mice.The left L4–6 spinal cord segment was obtained at 0,1,2,4 and 8 weeks after severing the sciatic nerve.mRNA expression profiles were generated by RNA sequencing.The sequencing results of spinal cord mRNA at 1,2,4,and 8 weeks after severing the sciatic nerve were compared with those at 0 weeks by bioinformatic analysis.We identified 1915 differentially expressed mRNAs in the spinal cord,of which 4,1909,and 2 were differentially expressed at 1,4,and 8 weeks after sciatic nerve injury,respectively.Sequencing results indicated that the number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury.These mRNAs were associated with the cellular response to lipid,ATP metabolism,energy coupled proton transmembrane transport,nuclear transcription factor complex,vacuolar proton-transporting V-type ATPase complex,inner mitochondrial membrane protein complex,tau protein binding,NADH dehydrogenase activity and hydrogen ion transmembrane transporter activity.Of these mRNAs,Sgk1,Neurturin and Gpnmb took part in cell growth and development.Pathway analysis showed that these mRNAs were mainly involved in aldosterone-regulated sodium reabsorption,oxidative phosphorylation and collecting duct acid secretion.Functional assessment indicated that these mRNAs were associated with inflammation and cell morphology development.Our findings show that the number and type of spinal cord mRNAs involved in changes at different time points after peripheral nerve injury were different.The number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury.These results provide reference data for finding new targets for the treatment of peripheral nerve injury,and for further gene therapy studies of peripheral nerve injury and repair.The study procedures were approved by the Ethics Committee of the Peking University People's Hospital(approval No.2017 PHC004)on March 5,2017.展开更多
Nerve scarring after peripheral nerve injury can severely hamper nerve regeneration and functional recovery.Further,the anti-inflammatory cytokine,interleukin-10,can inhibit nerve scar formation.Saikosaponin a(SSa) ...Nerve scarring after peripheral nerve injury can severely hamper nerve regeneration and functional recovery.Further,the anti-inflammatory cytokine,interleukin-10,can inhibit nerve scar formation.Saikosaponin a(SSa) is a monomer molecule extracted from the Chinese medicine,Bupleurum.SSa can exert anti-inflammatory effects in spinal cord injury and traumatic brain injury.However,it has not been shown whether SSa can play a role in peripheral nerve injury.In this study,rats were randomly assigned to three groups.In the sham group,the left sciatic nerve was directly sutured after exposure.In the sciatic nerve injury(SNI) + SSa and SNI groups,the left sciatic nerve was sutured and continuously injected daily with SSa(10 mg/kg) or an equivalent volume of saline for 7 days.Enzyme linked immunosorbent assay results demonstrated that at 7 days after injury,interleukin-10 level was considerably higher in the SNI + SSa group than in the SNI group.Masson staining and western blot assay demonstrated that at 8 weeks after injury,type I and III collagen content was lower and nerve scar formation was visibly less in the SNI + SSa group compared with the SNI group.Simultaneously,sciatic functional index and nerve conduction velocity were improved in the SNI + SSa group compared with the SNI group.These results confirm that SSa can increase the expression of the anti-inflammatory factor,interleukin-10,and reduce nerve scar formation to promote functional recovery of injured sciatic nerve.展开更多
Bacterial melanin, obtained from the mutant strain of Bacillus Thuringiensis, has been shown to promote recovery after central nervous system injury. It is hypothesized, in this study, that bacterial melanin can promo...Bacterial melanin, obtained from the mutant strain of Bacillus Thuringiensis, has been shown to promote recovery after central nervous system injury. It is hypothesized, in this study, that bacterial melanin can promote structural and functional recovery after peripheral nerve injury. Rats subjected to sciatic nerve transection were intramuscularly administered bacterial melanin. The sciatic nerve transected rats that did not receive intramuscular administration of bacterial melanin served as controls. Behavior tests showed that compared to control rats, the time taken for instrumental conditioned reflex recovery was significantly shorter and the ability to keep the balance on the rotating bar was significantly better in bacterial melanin-treated rats. Histomor- phological tests showed that bacterial melanin promoted axon regeneration after sciatic nerve injury. These findings suggest that bacterial melanin exhibits neuroprotective effects on injured sciatic nerve, contributes to limb motor function recovery, and therefore can be used for rehabil- itation treatment of peripheral nerve injury.展开更多
Previous studies have demonstrated that muscarinic, and nicotinic receptors increase free Ca2+ levels in the facial nerve nucleus via various channels following facial nerve injury. However, intracellular Ca2+ overl...Previous studies have demonstrated that muscarinic, and nicotinic receptors increase free Ca2+ levels in the facial nerve nucleus via various channels following facial nerve injury. However, intracellular Ca2+ overload can trigger either necrotic or apoptotic cell death. Gamma-aminobutyric acid (GABA), an important inhibitory neurotransmitter in the central nervous system, exists in the facial nerve nucleus. It is assumed that GABA negatively regulates free Ca2+ levels in the facial nerve nucleus. The present study investigated GABA type A (GABAA) receptor expression in the facial nerve nucleus in a rat model of facial nerve injury using immunohistochemistry and laser confocal microscopy, as well as the regulatory effects of GABAA receptor on nicotinic receptor response following facial nerve injury. Subunits α1, α3, α5, β1, β2, δ, and γ3 of GABAA receptors were expressed in the facial nerve nucleus following facial nerve injury. In addition, GABAA receptor expression significantly inhibited the increase in nicotinic receptor-mediated free Ca2+ levels in the facial nerve nucleus following facial nerve injury in a concentration-dependent fashion. These results suggest that GABAA receptors exhibit negative effects on nicotinic receptor responses following facial nerve injury.展开更多
Emerging evidence supports that the stress response to peripheral nerve injury extends beyond the injured neuron,with alterations in associated transcription factors detected both locally and remote to the lesion.Stre...Emerging evidence supports that the stress response to peripheral nerve injury extends beyond the injured neuron,with alterations in associated transcription factors detected both locally and remote to the lesion.Stress-induced nuclear translocation of the transcription factor forkhead class box O3a(FOXO3a)was initially linked to activation of apoptotic genes in many neuronal subtypes.However,a more complex role of FOXO3a has been suggested in the injury response of sensory neurons,with the injured neuron expressing less FOXO3a.To elucidate this response and test whether non-injured sensory neurons also alter FOXO3a expression,the temporal impact of chronic unilateral L4–6 spinal nerve transection on FOXO3a expression and nuclear localization in adult rat dorsal root ganglion neurons ipsilateral,contralateral or remote to injury relative to na?ve controls was examined.In na?ve neurons,high cytoplasmic and nuclear levels of FOXO3a colocalized with calcitonin gene related peptide,a marker of the nociceptive subpopulation.One hour post-injury,an acute increase in nuclear FOXO3a in small size injured neurons occurred followed by a significant decrease after 1,2 and 4 days,with levels increasing toward pre-injury levels by 1 week post-injury.A more robust biphasic response to the injury was observed in uninjured neurons contralateral to and those remote to injury.Nuclear levels of FOXO3a peaked at 1 day,decreased by 4 days,then increased by 1 week post-injury,a response mirrored in C4 dorsal root ganglion neurons remote to injury.This altered expression contralateral and remote to injury supports that spinal nerve damage has broader systemic impacts,a response we recently reported for another stress transcription factor,Luman/CREB3.The early decreased expression and nuclear localization of FOXO3a in the injured neuron implicate these changes in the cell body response to injury that may be protective.Finally,the broader systemic changes support the existence of stress/injury-induced humeral factor(s)influencing transcriptional and potentially behavioral changes in uninjured dorsal root ganglion neurons.Approval to conduct this study was obtained from the University of Saskatchewan Animal Research Ethics Board(protocol#19920164).展开更多
Percutaneous microballoon compression of the trigeminal ganglion is a brand new operative technique for the treatment of trigeminal neuralgia. However, it is unclear how the procedure mediates pain relief, and there a...Percutaneous microballoon compression of the trigeminal ganglion is a brand new operative technique for the treatment of trigeminal neuralgia. However, it is unclear how the procedure mediates pain relief, and there are no standardized criteria, such as compression pressure, com- pression time or balloon shape, for the procedure. In this study, percutaneous microballoon compression was performed on the rabbit trigeminal ganglion at a mean inflation pressure of 1,005 + 150 mmHg for 2 or 5 minutes. At 1, 7 and 14 days after percutaneous microballoon compression, the large-diameter myelinated nerves displayed axonal swelling, rupture and demy- elination under the electron microscope. Fragmentation of myelin and formation of digestion chambers were more evident after 5 minutes of compression. Image analyzer results showed that the diameter of trigeminal ganglion cells remained unaltered after compression. These experi- mental findings indicate that a 2-minute period of compression can suppress pain transduction. Immunohistochemical staining revealed that vascular endothelial growth factor expression in the ganglion cells and axons was significantly increased 7 days after trigeminal ganglion compression, however, the changes were similar after 2-minute compression and 5-minute compression. The upregulated expression of vascular endothelial growth factor in the ganglion cells after percu- taneous microballoon compression can promote the repair of the injured nerve. These findings suggest that long-term compression is ideal for patients with recurrent trigeminal neuralgia.展开更多
In this study, we loaded human umbilical cord mesenchymal stem cells onto human amniotic membrane with epithelial cells to prepare nerve conduits, i.e., a relatively closed nerve regeneration chamber. After neurolysis...In this study, we loaded human umbilical cord mesenchymal stem cells onto human amniotic membrane with epithelial cells to prepare nerve conduits, i.e., a relatively closed nerve regeneration chamber. After neurolysis, the injured radial nerve was enwrapped with the prepared nerve conduit, which was fixed to the epineurium by sutures, with the cell on the inner surface of the conduit. Simultaneously, a 1.0 mL aliquot of human umbilical cord mesenchymal stem cell suspension was injected into the distal and proximal ends of the injured radial nerve with 1.0 cm intervals. A total of 1.75 x 107 cells were seeded on the amniotic membrane. In the control group, patients received only neurolysis. At 12 weeks after cell transplantation, more than 80% of patients exhibited obvious improvements in muscular strength, and touch and pain sensations. In contrast, these improvements were observed only in 55-65% of control patients. At 8 and 12 weeks, muscular electrophysiological function in the region dominated by the injured radial nerve was significantly better in the transplantation group than the control group. After cell transplantation, no immunological rejections were observed. These findings suggest that human umbilical cord mesenchymal stem cell-loaded amniotic membrane can be used for the repair of radial nerve injury.展开更多
文摘Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving multifaceted cellular and molecular processes.The contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large gap.Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI.The recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.
基金supported by grants from the Department of Technology of Jilin Province,Nos.3D5195941430(to YSW),20190201087(to ZCK)the Department of Finance of Jilin Province,No.3D517DV93429(to ZCK)。
文摘The effect of platelet-rich plasma on nerve regeneration remains controversial.In this study,we established a rabbit model of sciatic nerve small-gap defects with preserved epineurium and then filled the gaps with platelet-rich plasma.Twenty-eight rabbits were divided into the following groups(7 rabbits/group):model,low-concentrati on PRP(2.5-3.5-fold concentration of whole blood platelets),medium-concentration PRP(4.5-6.5-fold concentration of whole blood platelets),and high-concentration PRP(7.5-8.5-fold concentration of whole blood platelets).Electrophysiological and histomorphometrical assessments and proteomics analysis we re used to evaluate regeneration of the sciatic nerve.Our results showed that platelet-rich plasma containing 4.5-6.5-and 7.5-8.5-fold concentrations of whole blood platelets promoted repair of sciatic nerve injury.Proteomics analysis was performed to investigate the possible mechanism by which platelet-rich plasma promoted nerve regeneration.Proteomics analysis showed that after sciatic nerve injury,platelet-rich plasma increased the expression of integrin subunitβ-8(ITGB8),which participates in angiogenesis,and differentially expressed proteins were mainly enriched in focal adhesion pathways.Additionally,two key proteins,ribosomal protein S27 a(RSP27 a)and ubiquilin 1(UBQLN1),which were selected after protein-protein interaction analysis,are involved in the regulation of ubiquitin levels in vivo.These data suggest that platelet-rich plasma promotes peripheral nerve regeneration after sciatic nerve injury by affecting angiogenesis and intracellular ubiquitin levels.
基金funded by the Project of 2022 Health Commission Technology Plan of Zhejiang Province(Project Number:2022KY1169)the 2022 Ningbo Natural Science Foundation Young Doctoral Project(Project Number:2022J027).
文摘Background:The underlying mechanism of sciatic nerve injury(SNI)is a common motor functional disorder,necessitates further research.Methods:A rat model of SNI was established,with the injury group subjected to compressive injury of the right sciatic nerve exposed at the midpoint of the thigh and the sham surgery group undergoing the same surgical procedure.An oxygen-glucose deprivation model was employed to simulate in vitro SNI in PC12 cells.Following data acquisition and quality control,differentially expressed proteins(DEPs)in each model were identified through differential analysis,and enrichment analysis was used to explore the potential functions and pathways of the DEPs.Venn diagrams were drawn,and DEPs from both in vivo and in vitro SNI models were imported into the STRING database to construct a protein-protein interaction network and screen for hub proteins.Results:After the peptide segments obtained from rat nerve blockade and PC12 cells met quality requirements,258 DEPs were identified in rat nerve samples,and 119 DEPs were screened in PC12 cells.Enrichment analysis revealed that DEPs in the rat model were predominantly concentrated in biological functions such as myogenic cell proliferation and signaling related to lipid and energy metabolism.DEPs in the in vitro model were mainly enriched in biological processes such as phagocytosis and were associated with lipid transport and metabolism.Two hub proteins,amyloid precursor protein(APP)and fibronectin 1(FN1),were identified through MCC,MCODE,and Degree scoring.Both PC12 cells and external validation sets showed relatively higher expression of APP and FN1 in injured samples.Results of gene set enrichment analysis indicated that these two proteins were associated with metabolic pathways,such as biosynthesis of glycosaminoglycan chondroitin sulfate and biosynthesis of unsaturated fatty acids.Conclusion:APP and FN1 are potential key molecules involved in SNI and are associated with various metabolic pathways in nerve repair.These findings provide a theoretical basis for the development of therapeutic targets for SNI.
基金supported by NIH Center Core Grant P30EY014801a Research to Prevent Blindness Unrestrictea Grant+3 种基金partially supported by the Walter G.Ross Foundationpartly supported by the Gutierrez Family Research Fundthe Camiener Family Glaucoma Research Fundthe National Natural Science Foundation of China(No.82201170 to XL)。
文摘Monocytes,including monocyte-derived macrophages and resident microglia,mediate many phases of optic nerve injury pathogenesis.Resident microglia respond first,followed by infiltrating macrophages which regulate neuronal inflammation,cell proliferation and differentiation,scar formation and tissue remodeling following optic nerve injury.However,microglia and macrophages have distinct functions which can be either beneficial or detrimental to the optic nerve depending on the spatial context and temporal sequence of their activity.These divergent effects are attributed to pro-and anti-inflammatory cytokines expressed by monocytes,crosstalk between monocyte and glial cells and even microglia-macrophage communication.In this review,we describe the dynamics and functions of microglia and macrophages in neuronal inflammation and regeneration following optic nerve injury,and their possible role as therapeutic targets for axonal regeneration.
基金supported by the National Key Research and Development Program of China, No. 2016YFC1101603 (to DYZ)the National Natural Science Foundation of China, Nos. 31640045 (to YHW), 81901251 (to ML)the Natural Science Foundation of Beijing of China, No. 7204323 (to ML)
文摘We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.
基金supported by the National Natural Science Foundation of China,No. 81801213 (to BP)Xuzhou Special Fund for Promoting Scientific and Technological Innovation,Nos. KC21177 (to BP),KC21195 (to HF)Science and Technology Project of Yili Kazak Autonomous Prefecture,No. YZ2019D006 (to HF)。
文摘Research has shown that long-chain noncoding RNAs(lncRNAs) are involved in the regulation of a variety of biological processes, including peripheral nerve regeneration, in part by acting as competing endogenous RNAs. c-Jun plays a key role in the repair of peripheral nerve injury. However, the precise underlying mechanism of c-Jun remains unclear. In this study, we performed microarray and bioinformatics analysis of mouse crush-injured sciatic nerves and found that the lncRNA Pvt1 was overexpressed in Schwann cells after peripheral nerve injury. Mechanistic studies revealed that Pvt1 increased c-Jun expression through sponging miRNA-214. We overexpressed Pvt1 in Schwann cells cultured in vitro and found that the proliferation and migration of Schwann cells were enhanced, and overexpression of miRNA-214 counteracted the effects of Pvt1 overexpression on Schwann cell proliferation and migration. We conducted in vivo analyses and injected Schwann cells overexpressing Pvt1 into injured sciatic nerves of mice. Schwann cells overexpressing Pvt1 enhanced the regeneration of injured sciatic nerves following peripheral nerve injury and the locomotor function of mice was improved. Our findings reveal the role of lncRNAs in the repair of peripheral nerve injury and highlight lncRNA Pvt1 as a novel potential treatment target for peripheral nerve injury.
基金National Natural Science Foundation of China,No.819 73305 (to ZQ)Science and Technology Planning Project of Guangzhou of China,No.20190401 0487 (to ZQ)+1 种基金Natural Science Foundation of Guangdong Province,China,No.2021A1515010897 (to TT)Discipline Construction Fund of Cen tral Peoples Hospital of Zhanjiang,Nos.2020A01 (to TT) and 2020A02 (to TT)。
文摘Epigenetic changes in the spinal cord play a key role in the initiation and maintenance of nerve injury-induced neuro pathic pain.N6-methyladenosine(m6A)is one of the most abundant internal RNA modifications and plays an essential function in gene regulation in many diseases.However,the global m6A modification status of mRNA in the spinal cord at different stages after neuropathic pain is unknown.In this study,we established a neuropathic pain model in mice by preserving the complete sural nerve and only damaging the common peroneal nerve.High-throughput methylated RNA immunoprecipitation sequencing res ults showed that after spared nerve injury,there were 55 m6A methylated and diffe rentially expressed genes in the spinal cord.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway results showed that m6A modification triggered inflammatory responses and apoptotic processes in the early stages after spared nerve injury.Over time,the diffe rential gene function at postoperative day 7 was enriched in "positive regulation of neurogenesis" and "positive regulation of neural precursor cell prolife ration." These functions suggested that altered synaptic morphological plasticity was a turning point in neuropathic pain formation and maintenance.Results at postoperative day 14 suggested that the persistence of neuropathic pain might be from lipid metabolic processes,such as "very-low-density lipoprotein particle clearance," "negative regulation of choleste rol transport" and "membrane lipid catabolic process." We detected the expression of m6A enzymes and found elevated mRNA expression of Ythdf2 and Ythdf3 after spared nerve injury modeling.We speculate that m6A reader enzymes also have an important role in neuropathic pain.These results provide a global landscape of mRNA m6A modifications in the spinal cord in the spared nerve injury model at diffe rent stages after injury.
基金supported by the National Natural Science Foundation of China, No. 81271088the Natural Science Foundation of Shanghai, No. 11ZR1423600
文摘To determine the value of dissecting the recurrent laryngeal nerve during thyroid surgery with respect to preventing recurrent laryngeal nerve injury, we retrospectively analyzed clinical data from 5 344 patients undergoing thyroidectomy. Among these cases, 548 underwent dissection of the recurrent laryngeal nerve, while 4 796 did not. There were 12 cases of recurrent laryngeal nerve injury following recurrent laryngeal nerve dissection (injury rate of 2.2%) and 512 cases of recurrenl laryngeal nerve injury in those not undergoing nerve dissection (injury rate of 10.7%). This difference remained statistically significant between the two groups in terms of type of thyroid disease, type of surgery, and number of surgeries. Among the 548 cases undergoing recurrent laryngeal nerve dissection, 128 developed anatomical variations of the recurrent laryngeal nerve (incidence rate of 23.4%), but no recurrent laryngeal nerve injury was found. In addition, the incidence of recurrent laryngeal nerve injury was significantly lower in patients with the infedor parathyroid gland and middle thyroid veins used as landmarks for locating the recurrent laryngeal nerve compared with those with the entry of the recurrent laryngeal nerve into the larynx as a landmark. These findings indicate that anatomical variations of the recurrent laryngeal nerve are common, and that dissecting the recurrent laryngeal nerve during thyroid surgery is an effective means of preventing nerve injury.
基金supported by grants from the National Natural Science Foundation of China,Grant No.81370982,31170946Key Program,Grant No.81130080+1 种基金the Scientific Research Foundation for Returned Scholars,Ministry of Education of Chinathe Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Claudin 14 has been shown to promote nerve repair and regeneration in the early stages of Wallerian degeneration (0-4 days) in rats with sciatic nerve injury, but the mechanism underlying this process remains poorly understood. This study reported the effects of claudin 14 on nerve degeneration and regeneration during early Wallerian degeneration. Claudin 14 expression was up-regulated in sciatic nerve 4 days after Wallerian degeneration. The altered expression of claudin 14 in Schwann cells resulted in expression changes of cytokines in vitro. Expression of claudin 14 affected c-Jun, but not Akt anal ERK1/2 patl^ways, l^urther studies reve^ed that enhanced expression of claudin 14 could promote Schwann cell proliferation and migration. Silencing of claudin 14 expression resulted in Schwann cell apoptosis and reduction in Schwann cell proliferation. Our data revealed the role of claudin 14 in early Wallerian degeneration, which may provide new insights into the molecular mechanisms of Wallerian degeneration.
基金supported by the National Natural Science Foundation of China,No.81370982,31170946Key Program,Grant No.81130080the Priority Academic Program Development of Jiangsu Higher Education Institutions in China
文摘Wallerian degeneration is a subject of major interest in neuroscience. A large number of genes are differentially regulated during the distinct stages of Wallerian degeneration: transcription factor activation, immune response, myelin cell differentiation and dedifferentiation. Although gene expression responses in the distal segment of the sciatic nerve after peripheral nerve injury are known, differences in gene expression between the proximal and distal segments remain unclear. In the present study in rats, we used microarrays to analyze changes in gene expression, biological processes and signaling pathways in the proximal and distal segments of sciatic nerves under- going Wallerian degeneration. More than 6,000 genes were differentially expressed and 20 types of expression tendencies were identified, mainly between proximal and distal segments at 7-14 days after injury. The differentially expressed genes were those involved in cell differentiation, cytokinesis, neuron differentiation, nerve development and axon regeneration. Furthermore, 11 biological processes were represented, related to responses to stimuli, cell apoptosis, inflammato- ry response, immune response, signal transduction, protein kinase activity, and cell proliferation. Using real-time quantitative PCR, western blot analysis and immunohistochemistry, microarray data were verified for four genes: aquaporin-4, interleukin 1 receptor-like 1, matrix metallopro- teinase-12 and periaxin. Our study identifies differential gene expression in the proximal and distal segments of a nerve during Wallerian degeneration, analyzes dynamic biological changes of these genes, and provides a useful platform for the detailed study of nerve injury and repair during Wallerian degeneration.
基金supported by the National Natural Science Foundation of China,No.81160158 and 30860290
文摘This study investigated the possible involvement of microRNAs in the regulation of genes that participate in peripheral neural regeneration. A microRNA microarray analysis was conducted and 23 microRNAs were identiifed whose expression was signiifcantly changed in rat dorsal root ganglia after sciatic nerve transection. The expression of one of the downregulated microRNAs, microRNA-214, was validated using quantitative reverse transcriptase-PCR. MicroRNA-214 was predicted to target the 3′-untranslated region of Slit-Robo GTPase-activating protein 3. In situ hybridization veriifed that microRNA-214 was located in the cytoplasm of dorsal root ganglia primary neurons and was downregulated following sciatic nerve transection. Moreover, a com-bination of in situ hybridization and immunohistochemistry revealed that microRNA-214 and Slit-Robo GTPase-activating protein 3 were co-localized in dorsal root ganglion primary neu-rons. Western blot analysis suggested that Slit-Robo GTPase-activating protein 3 was upregulated in dorsal root ganglion neurons after sciatic nerve transection. These data demonstrate that mi-croRNA-214 is located and differentially expressed in dorsal root ganglion primary neurons and may participate in regulating the gene expression of Slit-Robo GTPase-activating protein 3 after sciatic nerve transection.
基金supported by the National Natural Science Foundation of China,No.30901515Dalian Municipal Science and Technology Project Foundation in China,No.2009J22DW029
文摘Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve injury. However, the therapeutic effect of edaravone on peripheral nerve injury caused by mechanical factors is unknown. In the present study, we established a peripheral nerve injury model by crushing the sciatic nerve using hemostatic forceps, and then administered edaravone 3 mg/kg intraperitoneally. The sciatic functional index and superoxide dismutase activity of the sciatic nerve were increased, and the malondialdehyde level was decreased in animals in the edaravone group compared with those in the model group. Bcl-2 expression was increased, but Bax expres- sion was decreased in anterior horn cells of the L4-6 spinal cord segments. These results indicated that edaravone has a neuroprotective effect following peripheral nerve injury caused by mechan- ical factors through alleviating free radical damage to cells and inhibiting lipid peroxidation, as well as regulating apoptosis-related protein expression.
基金funded by the Key Project of Clinical Specialty of Ministry of Public Health,No.2007-353
文摘The magnitude of tensile stress and tensile strain at an anastomosis site under physiological stress is an important factor for the success of anastomosis following suturing in peripheral nerve injury treatment. Sciatic nerves from fresh adult cadavers were used to create models of sciatic nerve injury. The denervated specimens underwent epineurial and perineurial suturing. The elastic modulus (40.96 + 2.59 MPa) and Poisson ratio (0.37 + 0.02) of the normal sciatic nerve were measured by strain electrical measurement. A resistance strain gauge was pasted on the front, back left, and right of the edge of the anastomosis site after suturing. Strain electrical measurement results showed that the stress and strain values of the sciatic nerve following perineurial suturing were lower than those following epineurial suturing. Scanning electron microscopy revealed that the sciatic nerve fibers were disordered following epineurial compared with perineurial suturing. These results indicate that the effect of perineurial suturing in sciatic nerve injury repair is better than that of epineurial suturing.
基金supported by the National Natural Science Foundation of China,No.81671215(to XFY),No.31571002(to BGJ)the Natural Science Foundation of Beijing of China,No.7192215(to XFY)
文摘Peripheral nerve injury may trigger changes in mRNA levels in the spinal cord.Finding key mRNAs is important for improving repair after nerve injury.This study aimed to investigate changes in mRNAs in the spinal cord following sciatic nerve injury by transcriptomic analysis.The left sciatic nerve denervation model was established in C57 BL/6 mice.The left L4–6 spinal cord segment was obtained at 0,1,2,4 and 8 weeks after severing the sciatic nerve.mRNA expression profiles were generated by RNA sequencing.The sequencing results of spinal cord mRNA at 1,2,4,and 8 weeks after severing the sciatic nerve were compared with those at 0 weeks by bioinformatic analysis.We identified 1915 differentially expressed mRNAs in the spinal cord,of which 4,1909,and 2 were differentially expressed at 1,4,and 8 weeks after sciatic nerve injury,respectively.Sequencing results indicated that the number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury.These mRNAs were associated with the cellular response to lipid,ATP metabolism,energy coupled proton transmembrane transport,nuclear transcription factor complex,vacuolar proton-transporting V-type ATPase complex,inner mitochondrial membrane protein complex,tau protein binding,NADH dehydrogenase activity and hydrogen ion transmembrane transporter activity.Of these mRNAs,Sgk1,Neurturin and Gpnmb took part in cell growth and development.Pathway analysis showed that these mRNAs were mainly involved in aldosterone-regulated sodium reabsorption,oxidative phosphorylation and collecting duct acid secretion.Functional assessment indicated that these mRNAs were associated with inflammation and cell morphology development.Our findings show that the number and type of spinal cord mRNAs involved in changes at different time points after peripheral nerve injury were different.The number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury.These results provide reference data for finding new targets for the treatment of peripheral nerve injury,and for further gene therapy studies of peripheral nerve injury and repair.The study procedures were approved by the Ethics Committee of the Peking University People's Hospital(approval No.2017 PHC004)on March 5,2017.
基金financially supported by the National Natural Science Foundation of China,No.11672332,11102235,8167050417the National Key Research and Development Plan of China,No.2016YFC1101500+1 种基金the Key Science and Technology Support Foundation of Tianjin City of China,No.17YFZCSY00620the Natural Science Foundation of Tianjin City of China,No.15JCYBJC28600,17JCZDJC35400
文摘Nerve scarring after peripheral nerve injury can severely hamper nerve regeneration and functional recovery.Further,the anti-inflammatory cytokine,interleukin-10,can inhibit nerve scar formation.Saikosaponin a(SSa) is a monomer molecule extracted from the Chinese medicine,Bupleurum.SSa can exert anti-inflammatory effects in spinal cord injury and traumatic brain injury.However,it has not been shown whether SSa can play a role in peripheral nerve injury.In this study,rats were randomly assigned to three groups.In the sham group,the left sciatic nerve was directly sutured after exposure.In the sciatic nerve injury(SNI) + SSa and SNI groups,the left sciatic nerve was sutured and continuously injected daily with SSa(10 mg/kg) or an equivalent volume of saline for 7 days.Enzyme linked immunosorbent assay results demonstrated that at 7 days after injury,interleukin-10 level was considerably higher in the SNI + SSa group than in the SNI group.Masson staining and western blot assay demonstrated that at 8 weeks after injury,type I and III collagen content was lower and nerve scar formation was visibly less in the SNI + SSa group compared with the SNI group.Simultaneously,sciatic functional index and nerve conduction velocity were improved in the SNI + SSa group compared with the SNI group.These results confirm that SSa can increase the expression of the anti-inflammatory factor,interleukin-10,and reduce nerve scar formation to promote functional recovery of injured sciatic nerve.
文摘Bacterial melanin, obtained from the mutant strain of Bacillus Thuringiensis, has been shown to promote recovery after central nervous system injury. It is hypothesized, in this study, that bacterial melanin can promote structural and functional recovery after peripheral nerve injury. Rats subjected to sciatic nerve transection were intramuscularly administered bacterial melanin. The sciatic nerve transected rats that did not receive intramuscular administration of bacterial melanin served as controls. Behavior tests showed that compared to control rats, the time taken for instrumental conditioned reflex recovery was significantly shorter and the ability to keep the balance on the rotating bar was significantly better in bacterial melanin-treated rats. Histomor- phological tests showed that bacterial melanin promoted axon regeneration after sciatic nerve injury. These findings suggest that bacterial melanin exhibits neuroprotective effects on injured sciatic nerve, contributes to limb motor function recovery, and therefore can be used for rehabil- itation treatment of peripheral nerve injury.
基金a Grant from the Youth Research Foundation of Qingdao University,No.2007
文摘Previous studies have demonstrated that muscarinic, and nicotinic receptors increase free Ca2+ levels in the facial nerve nucleus via various channels following facial nerve injury. However, intracellular Ca2+ overload can trigger either necrotic or apoptotic cell death. Gamma-aminobutyric acid (GABA), an important inhibitory neurotransmitter in the central nervous system, exists in the facial nerve nucleus. It is assumed that GABA negatively regulates free Ca2+ levels in the facial nerve nucleus. The present study investigated GABA type A (GABAA) receptor expression in the facial nerve nucleus in a rat model of facial nerve injury using immunohistochemistry and laser confocal microscopy, as well as the regulatory effects of GABAA receptor on nicotinic receptor response following facial nerve injury. Subunits α1, α3, α5, β1, β2, δ, and γ3 of GABAA receptors were expressed in the facial nerve nucleus following facial nerve injury. In addition, GABAA receptor expression significantly inhibited the increase in nicotinic receptor-mediated free Ca2+ levels in the facial nerve nucleus following facial nerve injury in a concentration-dependent fashion. These results suggest that GABAA receptors exhibit negative effects on nicotinic receptor responses following facial nerve injury.
基金supported by Canadian Institutes of Health Research(CIHR)grants#74747 and#14238(both to VMKV)Natural Sciences and Science and Engineering Research Council(NSERC)of Canada grant(to VM)supported by University of Saskatchewan College of Graduate and Postdoctoral Studies Scholarships。
文摘Emerging evidence supports that the stress response to peripheral nerve injury extends beyond the injured neuron,with alterations in associated transcription factors detected both locally and remote to the lesion.Stress-induced nuclear translocation of the transcription factor forkhead class box O3a(FOXO3a)was initially linked to activation of apoptotic genes in many neuronal subtypes.However,a more complex role of FOXO3a has been suggested in the injury response of sensory neurons,with the injured neuron expressing less FOXO3a.To elucidate this response and test whether non-injured sensory neurons also alter FOXO3a expression,the temporal impact of chronic unilateral L4–6 spinal nerve transection on FOXO3a expression and nuclear localization in adult rat dorsal root ganglion neurons ipsilateral,contralateral or remote to injury relative to na?ve controls was examined.In na?ve neurons,high cytoplasmic and nuclear levels of FOXO3a colocalized with calcitonin gene related peptide,a marker of the nociceptive subpopulation.One hour post-injury,an acute increase in nuclear FOXO3a in small size injured neurons occurred followed by a significant decrease after 1,2 and 4 days,with levels increasing toward pre-injury levels by 1 week post-injury.A more robust biphasic response to the injury was observed in uninjured neurons contralateral to and those remote to injury.Nuclear levels of FOXO3a peaked at 1 day,decreased by 4 days,then increased by 1 week post-injury,a response mirrored in C4 dorsal root ganglion neurons remote to injury.This altered expression contralateral and remote to injury supports that spinal nerve damage has broader systemic impacts,a response we recently reported for another stress transcription factor,Luman/CREB3.The early decreased expression and nuclear localization of FOXO3a in the injured neuron implicate these changes in the cell body response to injury that may be protective.Finally,the broader systemic changes support the existence of stress/injury-induced humeral factor(s)influencing transcriptional and potentially behavioral changes in uninjured dorsal root ganglion neurons.Approval to conduct this study was obtained from the University of Saskatchewan Animal Research Ethics Board(protocol#19920164).
基金supported by a grant from Shengjing Hospital,China Medical University,China,No.201010252
文摘Percutaneous microballoon compression of the trigeminal ganglion is a brand new operative technique for the treatment of trigeminal neuralgia. However, it is unclear how the procedure mediates pain relief, and there are no standardized criteria, such as compression pressure, com- pression time or balloon shape, for the procedure. In this study, percutaneous microballoon compression was performed on the rabbit trigeminal ganglion at a mean inflation pressure of 1,005 + 150 mmHg for 2 or 5 minutes. At 1, 7 and 14 days after percutaneous microballoon compression, the large-diameter myelinated nerves displayed axonal swelling, rupture and demy- elination under the electron microscope. Fragmentation of myelin and formation of digestion chambers were more evident after 5 minutes of compression. Image analyzer results showed that the diameter of trigeminal ganglion cells remained unaltered after compression. These experi- mental findings indicate that a 2-minute period of compression can suppress pain transduction. Immunohistochemical staining revealed that vascular endothelial growth factor expression in the ganglion cells and axons was significantly increased 7 days after trigeminal ganglion compression, however, the changes were similar after 2-minute compression and 5-minute compression. The upregulated expression of vascular endothelial growth factor in the ganglion cells after percu- taneous microballoon compression can promote the repair of the injured nerve. These findings suggest that long-term compression is ideal for patients with recurrent trigeminal neuralgia.
基金the Science and Technology Foundation of Shenyang in China,No.F10-217-1-00
文摘In this study, we loaded human umbilical cord mesenchymal stem cells onto human amniotic membrane with epithelial cells to prepare nerve conduits, i.e., a relatively closed nerve regeneration chamber. After neurolysis, the injured radial nerve was enwrapped with the prepared nerve conduit, which was fixed to the epineurium by sutures, with the cell on the inner surface of the conduit. Simultaneously, a 1.0 mL aliquot of human umbilical cord mesenchymal stem cell suspension was injected into the distal and proximal ends of the injured radial nerve with 1.0 cm intervals. A total of 1.75 x 107 cells were seeded on the amniotic membrane. In the control group, patients received only neurolysis. At 12 weeks after cell transplantation, more than 80% of patients exhibited obvious improvements in muscular strength, and touch and pain sensations. In contrast, these improvements were observed only in 55-65% of control patients. At 8 and 12 weeks, muscular electrophysiological function in the region dominated by the injured radial nerve was significantly better in the transplantation group than the control group. After cell transplantation, no immunological rejections were observed. These findings suggest that human umbilical cord mesenchymal stem cell-loaded amniotic membrane can be used for the repair of radial nerve injury.