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
Objective The relationship between compressed dorsal root ganglion （DRG） neurons and firing pattern and sensitivity of neurons was studied in chronically the Hindmarsh-Rose （HR） neuronal model. Methods Spontane- o...Objective The relationship between compressed dorsal root ganglion （DRG） neurons and firing pattern and sensitivity of neurons was studied in chronically the Hindmarsh-Rose （HR） neuronal model. Methods Spontane- ous activities from single fibers of chronically compressed DRG neurons in rats were recorded, and divided into periodic and non-periodic firing patterns. The sensitivity of the two kinds of firing pattern neuron to sympathetic stimulation （SS） was compared. Result It was found that 27.3% of periodic firing neurons and 93.2% of non-periodic firing neurons responded to SS respectively （ periodic vs non-periodic, P 〈 0.01 ）. The responses to SS with different stimulation time were greater non-periodic firing neurons than periodic firing neurons （P 〈 0.01 ）. The non-periodic firing neurons obviously responded to SS. After the firing pattern of these neurons transformed to periodic firing pattern, their responses to SS disappeared or decreased obviously. The HR neuronal model exhibited a significantly greater response to perturbation in non-periodic （chaotic） firing pattern than in periodic firing pattern. Conelusion The non-periodic firing neurons with deterministic chaos are more sensitive to external stimuli than the periodic firing neurons.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
Objective: To study sympathetic-sensory coupling in chronically compressed dorsal root ganglion (DRG) neurons in rats. Methods: In chronically compressed DRG model, the spontaneous activity of single fiber from the in...Objective: To study sympathetic-sensory coupling in chronically compressed dorsal root ganglion (DRG) neurons in rats. Methods: In chronically compressed DRG model, the spontaneous activity of single fiber from the injured DRG neuron was recorded, and lumbar sympathetic trunk was electrical stimulated to study the sympathetic modulation of spontaneous activities in injured DRG neurons. Results: Fifty-seven percent of spontaneous active neurons of injured DRG responded to sympathetic stimulation. The responses included simple excitation, excitation followed by inhibition and simple inhibition. The responses enhanced with the increase of sympathetic stimulation time. The responses to sympathetic stimula- tion could be blocked by intravenously injection of phentolamine, a-adrenorecepor antagonist. Fifty-three percent of injured DRG responded to norepinephrine (NE). The responses to NE were similar to those induced by sympathetic stimulation. Conclusion: Sympathetic-sensory coupling is virtually present in chronic compressed DRG neurons. NE released from sympathetic nerve terminals acts on a-adrenorecepor to influence spontaneous activities of injured DRG neurons.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
Spasticity following spinal cord injury（SCI） results in functional deterioration and reduced quality of life. Herein, we report two SCI patients who presented with good response to pulsed radiofrequency（PRF） for t...Spasticity following spinal cord injury（SCI） results in functional deterioration and reduced quality of life. Herein, we report two SCI patients who presented with good response to pulsed radiofrequency（PRF） for the management of spasticity in the lower extremities. Patient 1（a 47-year-old man） had complete thoracic cord injury and showed a phasic spasticity on the extensor of both knees（3–4 beats clonus per every 30 seconds） and tonic spasticity（Modified Ashworth Scale： 3） on both hip adductors. Patient 2（a 64-yearold man） had incomplete cervical cord injury and showed a right ankle clonus（approximately 20 beats） when he walked. After the application of PRF to both L2 and L3 dorsal root ganglion（DRG）（patient 1） and right S1 DRG（patient 2） with 5 Hz and 5 ms pulsed width for 360 seconds at 45 V under the C-arm guide, all spasticity disappeared or was reduced. Moreover, the effects of PRF were sustained for approximately 6 months with no side effects. We believe that PRF treatment can be useful for patients with spasticity after SCI.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
In this study,we investigate how Schwann cells and dorsal root ganglion(DRG)neurons response to direct low-intensity pulsed ultrasound(LIPUS)stimuli in vitro.Primary Schwann cells and DRG were isolated from rat sciati...In this study,we investigate how Schwann cells and dorsal root ganglion(DRG)neurons response to direct low-intensity pulsed ultrasound(LIPUS)stimuli in vitro.Primary Schwann cells and DRG were isolated from rat sciatic nerve and spine,respectively.LIPUS with varied dose of intensity(low:250 mW/cm2,medium:500 m W/cm2,high:750 m W/cm2)were applied 5 min per time for every other day,and pro-myelination indicators of Schwann cell as well as neurite outgrowth of dorsal root ganglion neurons were analyzed.Our results demonstrated that LIPUS promoted Schwann cells activity and proliferation from day 3 at the highest intensity,and day 5 at all intensities.In addition,LIPUS boosted pro-myelination activities of Schwann cells,as evidenced by increased cell population that positive for immunohistochemical staining against S100,nerve growth factor receptor(NGFR)p75,glial fibrillary acidic protein(GFAP),myelin protein zero(P0),as well as up-regulation of GFAP,Protein 0,nerve growth factor(NGF),and brain derived neurotrophic factor(BDNF)genes.Furthermore,LIPUS significantly enhanced the neurite outgrowth of DRG,with the highest intensity exhibiting longest neurite outgrowth.Taken together,our results strongly improve the understanding of cellular mechanisms of ultrasonic therapies for peripheral nerve repair.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This work was supported by the National Natural Science Foundation of China （30030040）.
文摘Objective The relationship between compressed dorsal root ganglion （DRG） neurons and firing pattern and sensitivity of neurons was studied in chronically the Hindmarsh-Rose （HR） neuronal model. Methods Spontane- ous activities from single fibers of chronically compressed DRG neurons in rats were recorded, and divided into periodic and non-periodic firing patterns. The sensitivity of the two kinds of firing pattern neuron to sympathetic stimulation （SS） was compared. Result It was found that 27.3% of periodic firing neurons and 93.2% of non-periodic firing neurons responded to SS respectively （ periodic vs non-periodic, P 〈 0.01 ）. The responses to SS with different stimulation time were greater non-periodic firing neurons than periodic firing neurons （P 〈 0.01 ）. The non-periodic firing neurons obviously responded to SS. After the firing pattern of these neurons transformed to periodic firing pattern, their responses to SS disappeared or decreased obviously. The HR neuronal model exhibited a significantly greater response to perturbation in non-periodic （chaotic） firing pattern than in periodic firing pattern. Conelusion The non-periodic firing neurons with deterministic chaos are more sensitive to external stimuli than the periodic firing neurons.
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 National Natural Science Foundation of China, No. 39970242
文摘Objective: To study sympathetic-sensory coupling in chronically compressed dorsal root ganglion (DRG) neurons in rats. Methods: In chronically compressed DRG model, the spontaneous activity of single fiber from the injured DRG neuron was recorded, and lumbar sympathetic trunk was electrical stimulated to study the sympathetic modulation of spontaneous activities in injured DRG neurons. Results: Fifty-seven percent of spontaneous active neurons of injured DRG responded to sympathetic stimulation. The responses included simple excitation, excitation followed by inhibition and simple inhibition. The responses enhanced with the increase of sympathetic stimulation time. The responses to sympathetic stimula- tion could be blocked by intravenously injection of phentolamine, a-adrenorecepor antagonist. Fifty-three percent of injured DRG responded to norepinephrine (NE). The responses to NE were similar to those induced by sympathetic stimulation. Conclusion: Sympathetic-sensory coupling is virtually present in chronic compressed DRG neurons. NE released from sympathetic nerve terminals acts on a-adrenorecepor to influence spontaneous activities of injured DRG neurons.
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.
文摘Spasticity following spinal cord injury（SCI） results in functional deterioration and reduced quality of life. Herein, we report two SCI patients who presented with good response to pulsed radiofrequency（PRF） for the management of spasticity in the lower extremities. Patient 1（a 47-year-old man） had complete thoracic cord injury and showed a phasic spasticity on the extensor of both knees（3–4 beats clonus per every 30 seconds） and tonic spasticity（Modified Ashworth Scale： 3） on both hip adductors. Patient 2（a 64-yearold man） had incomplete cervical cord injury and showed a right ankle clonus（approximately 20 beats） when he walked. After the application of PRF to both L2 and L3 dorsal root ganglion（DRG）（patient 1） and right S1 DRG（patient 2） with 5 Hz and 5 ms pulsed width for 360 seconds at 45 V under the C-arm guide, all spasticity disappeared or was reduced. Moreover, the effects of PRF were sustained for approximately 6 months with no side effects. We believe that PRF treatment can be useful for patients with spasticity after SCI.
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Supported by the National Natural Science Foundation of China(81327003)
文摘In this study,we investigate how Schwann cells and dorsal root ganglion(DRG)neurons response to direct low-intensity pulsed ultrasound(LIPUS)stimuli in vitro.Primary Schwann cells and DRG were isolated from rat sciatic nerve and spine,respectively.LIPUS with varied dose of intensity(low:250 mW/cm2,medium:500 m W/cm2,high:750 m W/cm2)were applied 5 min per time for every other day,and pro-myelination indicators of Schwann cell as well as neurite outgrowth of dorsal root ganglion neurons were analyzed.Our results demonstrated that LIPUS promoted Schwann cells activity and proliferation from day 3 at the highest intensity,and day 5 at all intensities.In addition,LIPUS boosted pro-myelination activities of Schwann cells,as evidenced by increased cell population that positive for immunohistochemical staining against S100,nerve growth factor receptor(NGFR)p75,glial fibrillary acidic protein(GFAP),myelin protein zero(P0),as well as up-regulation of GFAP,Protein 0,nerve growth factor(NGF),and brain derived neurotrophic factor(BDNF)genes.Furthermore,LIPUS significantly enhanced the neurite outgrowth of DRG,with the highest intensity exhibiting longest neurite outgrowth.Taken together,our results strongly improve the understanding of cellular mechanisms of ultrasonic therapies for peripheral nerve repair.
