Role of neurotrophic factors in enhancing linear axonal growth of ganglionic sensory neurons in vitro

Neurotrophins play a major role in the regulation of neuronal growth such as neurite sprouting or regeneration in response to nerve injuries. The role of nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor in maintaining the survival of peripheral neurons remains poorly understood. In regenerative medicine, different modalities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. This study was to investigate the influence of nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor on the growth of neurites using two in vitro models of dorsal root ganglia explants and dorsal root ganglia-derived primary cell dissociated cultures. Quantitative data showed that the total neurite length and tortuosity were differently influenced by trophic factors. Nerve growth factor and, indirectly, brain-derived neurotrophic factor stimulate the tortuous growth of sensory fibers and the formation of cell clusters. Neurotrophin-3, however, enhances neurite growth in terms of length and linearity allowing for a more organized and directed axonal elongation towards a peripheral target compared to the other growth factors. These findings could be of considerable importance for any clinical application of neurotrophic factors in peripheral nerve regeneration. Ethical approval was obtained from the Regione Piemonte Animal Ethics Committee ASLTO1(file # 864/2016-PR) on September 14, 2016.

Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).

Cell replacement with stem cell-derived retinal ganglion cells from different protocols

Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.

Satellite glial cells in sensory ganglia play a wider role in chronic pain via multiple mechanisms

Satellite glial cells are unique glial cells that surround the cell body of primary sensory neurons.An increasing body of evidence suggests that in the presence of inflammation and nerve damage,a significant number of satellite glial cells become activated,thus triggering a series of functional changes.This suggests that satellite glial cells are closely related to the occurrence of chronic pain.In this review,we first summarize the morphological structure,molecular markers,and physiological functions of satellite glial cells.Then,we clarify the multiple key roles of satellite glial cells in chronic pain,including gap junction hemichannel Cx43,membrane channel Pannexin1,K channel subunit 4.1,ATP,purinergic P2 receptors,and a series of additional factors and their receptors,including tumor necrosis factor,glutamate,endothelin,and bradykinin.Finally,we propose that future research should focus on the specific sorting of satellite glial cells,and identify genomic differences between physiological and pathological conditions.This review provides an important perspective for clarifying mechanisms underlying the peripheral regulation of chronic pain and will facilitate the formulation of new treatment plans for chronic pain.

Solution-processing approach of nanomaterials toward an artificial sensory system

Artificial sensory systems have emerged as pivotal technologies to bridge the gap between the virtual and real-world,replicating human senses to interact intelligently with external stimuli.To practically apply artificial sensory systems in the real-world,it is essential to mass-produce nanomaterials with ensured sensitivity and selectivity,purify them for desired functions,and integrate them into large-area sensory devices through assembly techniques.A comprehensive understanding of each process parameter from material processing to device assembly is crucial for achieving a high-performing artificial sensory system.This review provides a technological framework for fabricating high-performance artificial sensory systems,covering material processing to device integrations.We introduce recent approaches for dispersing and purifying various nanomaterials including 0D,1D,and 2D nanomaterials.We then highlight advanced coating and printing techniques of the solution-processed nanomaterials based on representative three methods including(i)evaporation-based assembly,(ii)assisted assembly,and(iii)direct patterning.We explore the application and performances of these solution-processed materials and printing methods in fabricating sensory devices mimicking five human senses including vision,olfaction,gustation,hearing,and tactile perception.Finally,we suggest an outlook for possible future research directions to solve the remaining challenges of the artificial sensory systems such as ambient stability,device consistency,and integration with AI-based software.

Prediction of cell-cell communication patierns of dorsal root ganglion cells:single-cell RNA sequencing data analysis

Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system,and dorsal root ganglion neuron excitability affects pain perception.Dorsal root ganglion stimulation is a new approach for managing pain sensation.Knowledge of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management strategies.Here,we used the single-cell RNA-sequencing(scRNA-seq)database to investigate intercellular communication networks among dorsal root ganglion cells.We collected scRNA-seq data from six samples from three studies,yielding data on a total of 17,766 cells.Based on genetic profiles,we identified satellite glial cells,Schwann cells,neurons,vascular endothelial cells,immune cells,fibroblasts,and vascular smooth muscle cells.Further analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive,itch,touch,mechanical,heat,and cold sensations.Moreover,we predicted several distinct forms of intercellular communication among dorsal root ganglion cells,including cell-cell contact,secreted signals,extracellular matrix,and neurotransmitter-mediated signals.The data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b(A2B)receptor and glial cell line-derived neurotrophic factor family receptor alpha 1(GFRα-1).Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-1.Intrathecal injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent manner.Our results demonstrate the involvement of the A2B receptor in the modulation of itch sensation.Furthermore,our findings provide insight into dorsal root ganglion cell-cell communication patterns and mechanisms.Our results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.

Neuroprotective effects of resveratrol on retinal ganglion cells in glaucoma in rodents:A narrative review

Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and blindness.The damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pressure,oxidative stress,inflammation,and other neurodegenerative processes.As the disease progresses,the loss of RGCs leads to vision loss.Therefore,protecting RGCs from damage and promoting their survival are important goals in managing glaucoma.In this regard,resveratrol(RES),a polyphenolic phytoalexin,exerts antioxidant effects and slows down the evolution and progression of glaucoma.The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina.Additionally,RES plays protective roles in RGCs by promoting cell growth,reducing apoptosis,and decreasing oxidative stress in H_(2)O_(2)-exposed RGCs.RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways.RES could alleviate retinal function impairment by suppressing the hypoxia-i nducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway.Therefore,RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.

Casein kinase-2 inhibition promotes retinal ganglion cell survival after acute intraocular pressure elevation

Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma,the leading cause of irreversible blindness.We previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve injury.To investigate the underlying mechanism,in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor(4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole)by intravitreal injection.We found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating macrophages.Transcriptomic analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 inhibitors.Furthermore,casein kinase-2 inhibition downregulated the expression of genes(Cck,Htrsa,Nef1,Htrlb,Prph,Chat,Slc18a3,Slc5a7,Scn1b,Crybb2,Tsga10ip,and Vstm21)involved in intraocular pressure elevation.Our data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.

NLRP3 and autophagy in retinal ganglion cell inflammation in age-related macular degeneration:potential therapeutic implications

Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)inflammasomes,which may affect RGCs in retinal degenerative diseases.The NLRP3 inflammasome was a protein complex that,upon activation,produces caspase-1,mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases.Upregulated autophagy could inhibit NLRP3 inflammasome activation,while inhibited autophagy can promote NLRP3 inflammasome activation,which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina.The activated NLRP3 inflammasome could further inhibit autophagy,thus forming a vicious cycle that accelerated the damage and death of RGCs.This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration,providing a new perspective and direction for the treatment of retinal diseases.

Severe SARS-CoV-2 Infection: Late Impact on the Retinal Ganglion Cell Layer Thickness

Purpose: The involvement of the ocular anterior segment by SARS-CoV-2 has been the subject of many studies, however, the repercussions on the posterior segment, particularly on the different layers of the retina and optic nerve, are still little known. The purpose of this study was to evaluate the impact of severe COVID-19 on the retinal ganglion cell layer (RGCL) thickness. Methods: This observational, prospective and analytical study was performed in the Ophthalmology Department of the FACISA University Center, Campina Grande. Three groups were included: group I (control), 29 healthy individuals who had not severe COVID-19;group II (infirmary), 24 individuals who had COVID-19 and were hospitalized in the infirmary;and group III, 25 individuals who had severe COVID-19 and required Intense Care Unit (ICU). All individuals had ophthalmologic examination and assessment of RGCL thickness using Optical Coherence Tomography (OCT). Statistical tests required p ≤ 0.05 to reject the null hypothesis. Results: The mean of RGCL thickness was significantly reduced in individuals from GIII (77.9 ± 8.9 µm), as compared with GII (83.9 ± 10.9 µm) and GI (82.8 ± 6.5 µm) (p = 0.0027). The mean measurements from the retinal neve fiber layer (RNFL) of the optic nerve head were similar. However, when evaluated sectoral, the mean of RNFL at the temporal sector of the optic disc was significantly lower in group GIII (p Conclusion: The RGCL thickness from patients with severe COVID-19 was significantly reduced. This finding supports that the SARS-CoV-2 has systemic action and affinity for nerve cells, including those from the retina and are related to the severity of the infection.

Effect of Sonic hedgehog gene-modified bone marrow mesenchymal stem cells on graft-induced retinal gliosis and retinal ganglion cells survival in diabetic mice

AIM:To investigate the effects of Sonic hedgehog(Shh)gene-modified bone marrow mesenchymal stem cells(MSCs)on graft-induced retinal gliosis and retinal ganglion cells(RGCs)survival in diabetic mice.METHODS:Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs(MSC-Shh).Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs(MSC-Gfp;control)were administered in diabetic mice.After 4wk,the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography,and markers of gliosis were examined by immunofluorescence and Western blotting.The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence.The mechanisms underlying the effects of MSC-Shh was investigated.RESULTS:A significant reduction of proliferative vitreoretinopathy(PVR)was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp.Significant downregulation of glial fibrillary acidic protein(GFAP)was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp.The extracellular signal-regulated kinase 1/2(ERK1/2),protein kinase B(AKT)and phosphatidylin-ositol-3-kinase(PI3K)pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp.Brain-derived neurotrophic factor(BDNF)and ciliary neurotrophic factor(CNTF)levels were significantly increased in the host retina,and RGCs loss was significantly prevented after MSC-Shh administration.CONCLUSION:MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice.The ERK1/2,AKT and PI3K pathways are involved in this process.MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice.

Pain and immune function in patients undergoing gastric cancer surgery following stellate ganglion block with total intravenous anesthesia

BACKGROUND Stellate ganglion block is a commonly used sympathetic nerve block technique that restores the balance of the sympathetic and vagal nervous systems of the body and inhibits sympathetic nerve activity.AIM To analyze the effect of a stellate ganglion block combined with total diploma intravenous anesthesia on postoperative pain and immune function in patients undergoing laparoscopic radical gastric cancer(GC)surgery to provide a refe-rence basis for the formulation of anesthesia protocols for radical GC surgery.METHODS This study included 112 patients who underwent laparoscopic radical surgery for GC between January 2022 and March 2024.There was no restriction on sex.The patient grouping method used was a digital random table method,and the num-ber of cases in each group was 56.The control group was administered total intravenous anesthesia,and the observation group compounded the stellate gan-glion block according to the total intravenous anesthesia protocol.Postoperative hemodynamics,pain levels,and immune indices were compared between the groups.RESULTS The heart rate and mean arterial pressure in the observation group after in-tubation were lower than those in the control group(P<0.05).Pain levels were compared between the two groups at 2 hours,12 hours,24 hours,and 48 hours after surgery(P>0.05).The number of CD3+,CD4+,and CD4+/CD8+cells at the end of surgery was higher in the observation group than in the control group,and the number of CD8+cells was lower in the observation group than in the control group(P<0.05).There were no significant differences between the two groups in terms of propofol dosage,awakening time,extubation time,or postoperative adverse reactions(P>0.05).CONCLUSION The application of a stellate ganglion block combined with total intravenous anesthesia had no significant effect on postoperative pain levels in patients undergoing laparoscopic radical GC surgery.However,it can safely reduce the effect of surgery on the immune function of patients and is worth applying in clinical practice.

Inhibition of the NLRP3 inflammasome attenuates spiral ganglion neuron degeneration in aminoglycoside-induced hearing loss

Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target.In addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure.To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with kanamycin.We found that the mice exhibited auditory deficits following the acute loss of outer hair cells.Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time.Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 inflammasome.Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory cytokines.Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model.These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration.Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

Values of macular ganglion cell-inner plexiform layer and 10-2 visual field measurements in detecting and evaluating glaucoma

AIM:To assess the performance of macular ganglion cell-inner plexiform layer thickness(mGCIPLT)and 10-2 visual field(VF)parameters in detecting early glaucoma and evaluating the severity of advanced glaucoma.METHODS:Totally 127 eyes from 89 participants(36 eyes of 19 healthy participants,45 eyes of 31 early glaucoma patients and 46 eyes of 39 advanced glaucoma patients)were included.The relationships between the optical coherence tomography(OCT)-derived parameters and VF sensitivity were determined.Patients with early glaucoma were divided into eyes with or without central 10°of the VF damages(CVFDs),and the diagnostic performances of OCT-derived parameters were assessed.RESULTS:In early glaucoma,the mGCIPLT was significantly correlated with 10-2 VF pattern standard deviation(PSD;with average mGCIPLT:β=-0.046,95%CI,-0.067 to-0.024,P<0.001).In advanced glaucoma,the mGCIPLT was related to the 24-2 VF mean deviation(MD;with average mGCIPLT:β=0.397,95%CI,0.199 to 0.595,P<0.001),10-2 VF MD(with average mGCIPLT:β=0.762,95%CI,0.485 to 1.038,P<0.001)and 24-2 VF PSD(with average mGCIPLT:β=0.244,95%CI,0.124 to 0.364,P<0.001).Except for the minimum and superotemporal mGCIPLT,the decrease of mGCIPLT in early glaucomatous eyes with CVFDs was more severe than that of early glaucomatous eyes without CVFDs.The area under the curve(AUC)of the average mGCIPLT(AUC=0.949,95%CI,0.868 to 0.982)was greater than that of the average circumpapillary retinal nerve fiber layer thickness(cpRNFLT;AUC=0.827,95%CI,0.674 to 0.918)and rim area(AUC=0.799,95%CI,0.610 to 0.907)in early glaucomatous eyes with CVFDs versus normal eyes.CONCLUSION:The 10-2 VF and mGCIPLT parameters are complementary to 24-2 VF,cpRNFLT and ONH parameters,especially in detecting early glaucoma with CVFDs and evaluating the severity of advanced glaucoma in group level.

Etomidate protects retinal ganglion cells from hydrogen peroxide-induced injury via Nrf2/HO-1 pathway

AIM:To determine whether etomidate(ET)has a protective effect on retinal ganglion cells(RGCs)injured with hydrogen peroxide(H_(2)O_(2))and to explore the potential mechanism underlying the antioxidative stress effect of ET.METHODS:Cultured RGCs were identified by double immunofluorescent labeling of microtubule-associated protein 2 and Thy1.1.An injury model of H_(2)O_(2)-induced RGCs oxidative stress was established in vitro.Cells were pretreated with different concentrations of ET(1,5,and 10μmol/L)for 4h,followed by further exposure to H_(2)O_(2)at 1000μmol/L.Cell counting kit 8 and Annexin V/propidium iodide assays were applied to detect the viabilities and apoptosis rates of the RGCs at 12,24,and 48h after H_(2)O_(2)stimulation.The levels of nitric oxide,malondialdehyde,and glutathione in culture media were measured at these time points.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blot were performed to observe the effects of ET on the messenger RNA and protein expression of inducible nitric oxide synthase(iNOS),nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),glutathione peroxidase 1 and the level of conjugated acrolein in RGCs at 12,24,and 48h after H_(2)O_(2)stimulation and in the retina at 12h after optic nerve transection(ONT).RESULTS:The applications of 5 and 10μmol/L of ET significantly increased the viability of RGCs.Results from qRT-PCR indicated a decrease in the expression of iNOS and an increase in the expressions of Nrf2 and HO-1 in ETpretreated RGCs at 12,24 and 48h after H_(2)O_(2)stimulation,as well as in ET-treated retinas at 12h after ONT.Western blot analysis revealed a decrease in the expression of iNOS and levels of conjugated acrolein,along with an increase in the expressions of Nrf2 and HO-1 in ET-pretreated RGCs in vitro and ET-treated retinas in vivo.CONCLUSION:ET is a neuroprotective agent in primary cultured RGCs injured by H_(2)O_(2).The effect of ET is dosedependent with the greatest effect being at 10μmol/L.ET plays an antioxidant role by inhibiting iNOS,up-regulating Nrf2/HO-1,decreasing the production of acrolein,and increasing the scavenge of acrolein.

Ultrasound-guided sphenopalatine ganglion block for effective analgesia during awake fiberoptic nasotracheal intubation: A case report

BACKGROUND Awake fiberoptic nasotracheal intubation(AFNI)is the preferred airway ma-nagement strategy for patients with difficult airways.However,this procedure can cause significant physical and psychological distress.This case report explores the application of a sphenopalatine ganglion(SPG)block as an alternative anal-gesic modality to mitigate the discomfort associated with AFNI.CASE SUMMARY A 63-year-old female with a history of right maxillary osteosarcoma underwent craniotomy for a suspected malignant brain lesion.The patient’s medical history included prior surgery,chemotherapy,and radiation therapy,resulting in signi-ficant jaw impairment and limited neck mobility.Considering the anticipated air-way challenges,AFNI was planned.A SPG block was performed under real-time ultrasound guidance,providing effective analgesia during nasotracheal intuba-tion.CONCLUSION The SPG block represents a promising analgesic approach in AFNI,offering po-tential benefits in alleviating pain involving the nasal and nasopharyngeal regions as well as improving patient cooperation.

Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

Analysis of the Necessity of Stellate Ganglion Block after Anesthesia to Reduce the Risk of Cardiovascular Accidents in Coronary Heart Disease

Objective:To adjust the sympathetic nervous system through preoperative ultrasound-guided stellate ganglion block and to explore and analyze the situation and necessity of postanesthesia stellate ganglion block to reduce the risk of cardiovascular accidents in coronary heart disease.Methods:80 patients with cardiovascular risk factors in Songshan Hospital of Chifeng were selected,and the time span would cover from October 2022 to June 2024,with 80 cases of elective surgery and combined coronary heart disease.They will be randomly divided into blocked groups and conventional groups,40 cases each.Conventional block was performed after anesthesia in patients in the conventional group,and planetary ganglion block was performed after anesthesia in patients in the blocked group.The cardiovascular responses of patients in the two groups were observed,and the number of intraoperative cardiovascular active drugs and the occurrence of cardiovascular adverse events were recorded in patients in the two groups.Results:Analysis of the mean arterial pressure(MAP)and heart rate(HR)values of the two groups of patients at the time points before anesthesia(T0),the moment of tracheal intubation(T1),the moment of surgical skin cutting(T2),the end of the operation(T3),and the 6h postoperative period(T4)showed that the MAP and HR of the blocked group were lower than those of the conventional group at the time points of T1 to T4,and the differences in MAP and HR values of the two groups in different time points compared with the T0 time point were statistically significant(P<0.05)and the differences in cardiovascular response(P<0.05)were statistically significant(P<0.05).significance(P<0.05).The number of intraoperative cardiovascular active drugs used in the blocked group was shorter than that in the conventional group,and the incidence of cardiovascular adverse events was lower than that in the conventional group,with a statistically significant difference(P<0.05).Conclusion:By implementing preoperative ultrasound-guided stellate ganglion block in patients with cardiovascular risk factors,the frequency and degree of coronary heart disease symptoms will be reduced,thus reducing the risk of patients,which is worth promoting.

The dorsal root ganglion as a target for neurorestoration in neuropathic pain

Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.During the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord

Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically poor.We used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic nerves.We have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor recovery.Furthermore,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target muscles.In this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic nerve.Young adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of PEG.Compound action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury site.The success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days postoperatively.At 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish peroxidase.PEG-fusion repair reestablished axonal continuity.Compared to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal areas.Unexpectedly,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repair.This central reorganization may contribute to the improved behavioral recovery seen after PEG-fusion repair,supporting the use of this novel repair methodology over currently available treatments.