Short-term, low-frequency electrical stimulation of neural tissues significantly enhances axonal regeneration of peripheral nerves following injury. However, little is known about the mechanisms of electrical stimulat...Short-term, low-frequency electrical stimulation of neural tissues significantly enhances axonal regeneration of peripheral nerves following injury. However, little is known about the mechanisms of electrical stimulation to induce neurite outgrowth. In the present study, short-term, low-frequency electrical stimulation, using identical stimulation parameters of in vivo experiments, was administered to in vitro dorsal root ganglion （DRG） neurons. Enhanced neurite outgrowth, as well as synthesis and release of brain-derived neurotrophic factor （BDNF）, were examined in electrical stimulation-treated DRG neuronal cultures. Because the effects of electrical stimulation on neuronal intracellular signaling molecules are less reported, classic calcium intracellular signals are directly or indirectly involved in electrical stimulation effects on neurons. Cultured DRG neurons were pretreated with the calcium channel blocker nifedipine, followed by electrical stimulation. Results suggested that electrical stimulation not only promoted in vitro neurite outgrowth, but also enhanced BDNF expression. However, nifedipine reduced electrical stimulation-enhanced neurite outgrowth and BDNF biosynthesis. These results suggest that the promoting effects of electrical stimulation on DRG neurite outgrowth could be associated with altered calcium influx, which is involved induction of neuronal BDNF expression and secretion.展开更多
Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximat...Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 m A and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers.展开更多
Our previous study found that some trigeminal ganglion（TG） nerve endings in the inner walls of rat anterior chambers were mechanosensitive, and transient receptor potential ankyrin 1（TRPA1） was an essential mechan...Our previous study found that some trigeminal ganglion（TG） nerve endings in the inner walls of rat anterior chambers were mechanosensitive, and transient receptor potential ankyrin 1（TRPA1） was an essential mechanosensitive channel in the membrane. To address the effect of cannabinoids on the mechanosensitive TG nerve endings in the inner walls of anterior chambers of rat eye, we investigated the effect of the（R）-（＋）-WIN55, 212-2 mesylate salt（WIN）, a synthetic cannabinoid on their cell bodies in vitro. Rat TG neurons innervating the inner walls of the anterior chambers were labeled by 1,1＇-dilinoleyl-3,3,3＇,3＇-tetramethylindocarbocyanine, 4-chlorobenzenesulfona（FAST Di I）. Whole cell patch clamp was performed to record the currents induced by drugs and mechanical stimulation. Mechanical stimulation was applied to the neurons by buffer ejection. WIN evoked inward currents via TRPA1 activation in FAST Di I-labeled TG neurons. WIN enhanced mechanosensitive currents via TRPA1 activation in FAST Di I-labeled TG neurons. Our results indicate that cannabinoids can enhance the mechanosensitivity of TG endings in the inner walls of anterior chambers of rat eye via TRPA1 activation.展开更多
Previous studies on the mechanisms of peripheral nerve injury(PNI)have mainly focused on the pathophysiological changes within a single injury site.However,recent studies have indicated that within the central nervous...Previous studies on the mechanisms of peripheral nerve injury(PNI)have mainly focused on the pathophysiological changes within a single injury site.However,recent studies have indicated that within the central nervous system,PNI can lead to changes in both injury sites and target organs at the cellular and molecular levels.Therefore,the basic mechanisms of PNI have not been comprehensively understood.Although electrical stimulation was found to promote axonal regeneration and functional rehabilitation after PNI,as well as to alleviate neuropathic pain,the specific mechanisms of successful PNI treatment are unclear.We summarize and discuss the basic mechanisms of PNI and of treatment via electrical stimulation.After PNI,activity in the central nervous system(spinal cord)is altered,which can limit regeneration of the damaged nerve.For example,cell apoptosis and synaptic stripping in the anterior horn of the spinal cord can reduce the speed of nerve regeneration.The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI.This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission.The injured site of the peripheral nerve is also an important factor affecting post-PNI repair.After PNI,the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site.A slow speed of axon regeneration leads to low nerve regeneration.Therefore,it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site.From the perspective of target organs,long-term denervation can cause atrophy of the corresponding skeletal muscle,which leads to abnormal sensory perception and hyperalgesia,and finally,the loss of target organ function.The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping,addressing the excessive excitability of the dorsal root ganglion,alleviating neuropathic pain,improving neurological function,and accelerating nerve regeneration.Electrical stimulation of target organs can reduce the atrophy of denervated skeletal muscle and promote the recovery of sensory function.Findings from the included studies confirm that after PNI,a series of physiological and pathological changes occur in the spinal cord,injury site,and target organs,leading to dysfunction.Electrical stimulation may address the pathophysiological changes mentioned above,thus promoting nerve regeneration and ameliorating dysfunction.展开更多
Effective and safe electrical stimulation of the retinal ganglion cells is at the heart of retinal prosthesis design.However,the effectiveness and safety demand of the electrical stimulation is often at odds against e...Effective and safe electrical stimulation of the retinal ganglion cells is at the heart of retinal prosthesis design.However,the effectiveness and safety demand of the electrical stimulation is often at odds against each other.Besides,the nerve fiber layer above retinal ganglion cells limits the spatial resolution of stimulation.Also,current retinal prosthesis still cannot selectively activate the ON or OFF visual pathways,thus cannot relay the correct luminance information to the brain.With decades of development,the stimulation protocol for retinal implants began to tackle these problems.We believe that a novel design of electrical stimulation scheme,combined with gene therapy technique,can improve the selectivity and spatial resolution of retinal implants and further lower the damage caused by electric stimulation.展开更多
By in situ hybridization histochemistry, the changes of preprotachykinin (PPT) mRNA expression were examined in the neurons of adjacent thoracal dorsal root ganglion (DRG) after a strong electric stimulation to an int...By in situ hybridization histochemistry, the changes of preprotachykinin (PPT) mRNA expression were examined in the neurons of adjacent thoracal dorsal root ganglion (DRG) after a strong electric stimulation to an intact dorsal cutaneous branch and the cut distal part of left T 9 thoracal spinal nerve of rat. There was a significant increase of the number of neurons expressing PPT mRNA in the ipsilateral T 8, T 9 and T 10 DRG of the animals given electric stimulation to intact spinal nerve branch 24 h after the electric stimulation. The same increase was found in the ipsilateral T 8 and T 10 DRG of the animals given electric stimulation to the distal part of spinal nerve branch. While no change was found in the DRG of the contralateral side of these animals. The present results showed that the antidromic electric stimulation strengthened the biosynthesis of PPT mRNA in adjacent DRG. These findings suggested that there was information transmission across segments between two sensory nerve endings and some bioactive substances such as SP might play important roles in the information transmission across segments of spinal cord.展开更多
基金the Shanghai Leading Academic Discipline Project,No.S30201the Doctoral Research Foundation of Nanchang University
文摘Short-term, low-frequency electrical stimulation of neural tissues significantly enhances axonal regeneration of peripheral nerves following injury. However, little is known about the mechanisms of electrical stimulation to induce neurite outgrowth. In the present study, short-term, low-frequency electrical stimulation, using identical stimulation parameters of in vivo experiments, was administered to in vitro dorsal root ganglion （DRG） neurons. Enhanced neurite outgrowth, as well as synthesis and release of brain-derived neurotrophic factor （BDNF）, were examined in electrical stimulation-treated DRG neuronal cultures. Because the effects of electrical stimulation on neuronal intracellular signaling molecules are less reported, classic calcium intracellular signals are directly or indirectly involved in electrical stimulation effects on neurons. Cultured DRG neurons were pretreated with the calcium channel blocker nifedipine, followed by electrical stimulation. Results suggested that electrical stimulation not only promoted in vitro neurite outgrowth, but also enhanced BDNF expression. However, nifedipine reduced electrical stimulation-enhanced neurite outgrowth and BDNF biosynthesis. These results suggest that the promoting effects of electrical stimulation on DRG neurite outgrowth could be associated with altered calcium influx, which is involved induction of neuronal BDNF expression and secretion.
基金supported by the Key Scientific and Technological Program of Linyi City of China,No.201313026
文摘Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 m A and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers.
基金supported by the National Natural Science Foundation of China(No.81070727)
文摘Our previous study found that some trigeminal ganglion（TG） nerve endings in the inner walls of rat anterior chambers were mechanosensitive, and transient receptor potential ankyrin 1（TRPA1） was an essential mechanosensitive channel in the membrane. To address the effect of cannabinoids on the mechanosensitive TG nerve endings in the inner walls of anterior chambers of rat eye, we investigated the effect of the（R）-（＋）-WIN55, 212-2 mesylate salt（WIN）, a synthetic cannabinoid on their cell bodies in vitro. Rat TG neurons innervating the inner walls of the anterior chambers were labeled by 1,1＇-dilinoleyl-3,3,3＇,3＇-tetramethylindocarbocyanine, 4-chlorobenzenesulfona（FAST Di I）. Whole cell patch clamp was performed to record the currents induced by drugs and mechanical stimulation. Mechanical stimulation was applied to the neurons by buffer ejection. WIN evoked inward currents via TRPA1 activation in FAST Di I-labeled TG neurons. WIN enhanced mechanosensitive currents via TRPA1 activation in FAST Di I-labeled TG neurons. Our results indicate that cannabinoids can enhance the mechanosensitivity of TG endings in the inner walls of anterior chambers of rat eye via TRPA1 activation.
基金supported by the National Natural Science Foundation of China,No.81801787(to XZS)China Postdoctoral Science Foundation,No.2018M640238(to XZS)the Natural Science Foundation of Tianjin,No.20JCQNJC01690(XLC).
文摘Previous studies on the mechanisms of peripheral nerve injury(PNI)have mainly focused on the pathophysiological changes within a single injury site.However,recent studies have indicated that within the central nervous system,PNI can lead to changes in both injury sites and target organs at the cellular and molecular levels.Therefore,the basic mechanisms of PNI have not been comprehensively understood.Although electrical stimulation was found to promote axonal regeneration and functional rehabilitation after PNI,as well as to alleviate neuropathic pain,the specific mechanisms of successful PNI treatment are unclear.We summarize and discuss the basic mechanisms of PNI and of treatment via electrical stimulation.After PNI,activity in the central nervous system(spinal cord)is altered,which can limit regeneration of the damaged nerve.For example,cell apoptosis and synaptic stripping in the anterior horn of the spinal cord can reduce the speed of nerve regeneration.The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI.This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission.The injured site of the peripheral nerve is also an important factor affecting post-PNI repair.After PNI,the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site.A slow speed of axon regeneration leads to low nerve regeneration.Therefore,it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site.From the perspective of target organs,long-term denervation can cause atrophy of the corresponding skeletal muscle,which leads to abnormal sensory perception and hyperalgesia,and finally,the loss of target organ function.The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping,addressing the excessive excitability of the dorsal root ganglion,alleviating neuropathic pain,improving neurological function,and accelerating nerve regeneration.Electrical stimulation of target organs can reduce the atrophy of denervated skeletal muscle and promote the recovery of sensory function.Findings from the included studies confirm that after PNI,a series of physiological and pathological changes occur in the spinal cord,injury site,and target organs,leading to dysfunction.Electrical stimulation may address the pathophysiological changes mentioned above,thus promoting nerve regeneration and ameliorating dysfunction.
基金This study was supported by National Key R&D Program of China(Grant No.2017YFC0111202)(Z Xu)National Natural Science Foundation of China(Grant No.31800871)(Z Xu)Shenzhen Science and Technology Research Program(Grant No.JCYJ20170818163342873)(Z Xu).
文摘Effective and safe electrical stimulation of the retinal ganglion cells is at the heart of retinal prosthesis design.However,the effectiveness and safety demand of the electrical stimulation is often at odds against each other.Besides,the nerve fiber layer above retinal ganglion cells limits the spatial resolution of stimulation.Also,current retinal prosthesis still cannot selectively activate the ON or OFF visual pathways,thus cannot relay the correct luminance information to the brain.With decades of development,the stimulation protocol for retinal implants began to tackle these problems.We believe that a novel design of electrical stimulation scheme,combined with gene therapy technique,can improve the selectivity and spatial resolution of retinal implants and further lower the damage caused by electric stimulation.
文摘By in situ hybridization histochemistry, the changes of preprotachykinin (PPT) mRNA expression were examined in the neurons of adjacent thoracal dorsal root ganglion (DRG) after a strong electric stimulation to an intact dorsal cutaneous branch and the cut distal part of left T 9 thoracal spinal nerve of rat. There was a significant increase of the number of neurons expressing PPT mRNA in the ipsilateral T 8, T 9 and T 10 DRG of the animals given electric stimulation to intact spinal nerve branch 24 h after the electric stimulation. The same increase was found in the ipsilateral T 8 and T 10 DRG of the animals given electric stimulation to the distal part of spinal nerve branch. While no change was found in the DRG of the contralateral side of these animals. The present results showed that the antidromic electric stimulation strengthened the biosynthesis of PPT mRNA in adjacent DRG. These findings suggested that there was information transmission across segments between two sensory nerve endings and some bioactive substances such as SP might play important roles in the information transmission across segments of spinal cord.
