Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus.It is one of the major resultants of pharmacoresistance and...Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus.It is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy,but still lacks effective treatments.Here,we aimed to test the effects of low-frequency stimulation(LFS)at the subiculum for secondary epileptogenesis in a mouse model.Here,secondary epileptogenesis was simulated at regions both contralateral and ipsilateral to the primary focus by applying successive kindling stimuli.Mice kindled at the right CA3 showed higher seizure susceptibilities at both the contralateral CA3 and the ipsilateral entorhinal cortex and had accelerated kindling processes compared with naive mice.LFS at the ipsilateral subiculum during the primary kindling progress at the right CA3 effectively prevented secondary epileptogenesis at both the contralateral CA3 and the ipsilateral entorhinal cortex,characterized by decreased seizure susceptibilities and a retarded kindling process at those secondary foci.Only application along with the primary epileptogenesis was effective.Notably,the effects of LFS on secondary epileptogenesis were associated with its inhibitory effect at the secondary focus through interfering with the enhancement of synaptic connections between the primary and secondary foci.These results imply that LFS at the subiculum is an effective preventive strategy for extensive secondary epileptogenesis in temporal lobe epilepsy and present the subiculum as a target with potential translational importance.展开更多
Acupuncturea representative and historical treatment in traditional Chinese medicine(TCM),has been used to cure diseases for Chinese people in the past centuries.Since the late 1990s,acupuncture has been further accep...Acupuncturea representative and historical treatment in traditional Chinese medicine(TCM),has been used to cure diseases for Chinese people in the past centuries.Since the late 1990s,acupuncture has been further accepted worldwide.The World Health Organization(WHO)proposed Clinical Research Specification for acupuncture in 1995 and the US Food and Drug Administration(FDA)approved acupuncture as a complementary and alternative therapy for various kinds of diseases in 1996,with clinical advantages such as convenience and effectiveness[1].Cumulative evidence has proved that acupuncture could produce different degrees of efficacy for treating various kinds of diseases(such as neuropathic pain,migraine,Parkinson's disease et al.)and alleviate symptoms[2-4].However,unlike its evidence-based efficacies.展开更多
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 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.展开更多
Background:The blood-brain barrier(BBB)restricts the effective penetration of anti-seizure drugs(ASDs)into the brain,resulting in unwanted peripheral side effects of ASDs at therapeutic doses.Electroacupuncture(EA)has...Background:The blood-brain barrier(BBB)restricts the effective penetration of anti-seizure drugs(ASDs)into the brain,resulting in unwanted peripheral side effects of ASDs at therapeutic doses.Electroacupuncture(EA)has shown good efficiency in enhancing the drug molecules’permeability of BBB.Objective:We aimed to test the hypothesis that EA could improve the efficacy of ASDs for acute epileptic seizures by increasing their intracerebral concentrations.Methods:Firstly,quantitative analysis of electroacupuncture-mediated alterations in blood-brain barrier per-meability was performed involved two metrics:(1)Evans Blue penetration measured by the in vivo imaging system(IVIS)fluorescence imaging,and(2)brain tissue drug levels analyzed with high-performance liquid chromatography-mass spectrometry(HPLC)following intraperitoneal injection of ASDs,both experiments were performed after EA and intraperitoneal injection.Next,assessment of anti-seizure efficacy in models,as follow:post-electroacupuncture stimulation at GV20 and GV16,therapeutic and sub-doses of ASDs were delivered via intraperitoneal injection.Seizure susceptibility was evaluated using two distinct provocation methods:the clas-sic maximal electroshock tests and the pentylenetetrazol(i.p.)treatments,with seizure intensity being record.Lastly,the safety profile of electroacupuncture was preliminarily evaluated through open field test(OFT)and hot plate experiments.Results:We initially confirmed that EA was capable of enhancing the permeability of the BBB and increasing the intra-cerebral concentration of valproate acid.Then,behavioral experiments confirmed that EA combined with ASD exhibited superior efficacy compared to ASD monotherapy for acute seizures in both models.This enhancing efficacy could be extended to different ASDs with distinct acting mechanisms,including valproate acid,lamotrigine,lacosamide,and levetiracetam.And the electroacupuncture stimulation parameters were confirmed to be safe in mice through comprehensive behavioral evaluation.Conclusion:The results of the present study indicated that EA could improve the therapeutic efficacy of ASDs by enhancing the concentration of drugs in the brain,and provided a blueprint for better anti-seizure management with potential translational significance.展开更多
Background:Epilepsy is characterized by acute recurrent seizures.The control of seizures is largely hampered by the tolerance to current anti-seizure drugs.Complementary anti-convulsant pharmacotherapies are urgently ...Background:Epilepsy is characterized by acute recurrent seizures.The control of seizures is largely hampered by the tolerance to current anti-seizure drugs.Complementary anti-convulsant pharmacotherapies are urgently needed.Objective:Here,we aimed to investigate the anti-convulsant effects of Xingnaojing Injection(XNJ)which is an approved Traditional Chinese Medicine injection on different acute seizure models in mice.Methods:The effects of XNJ were tested on the maximal electroshock(MES),pentylenetetrazol(PTZ)and kainic acid(KA)acute seizure models.Also,whether XNJ can directly inhibit hippocampal neuronal firings were exam-ined by in vitro electrophysiology.Results:XNJ could shorten the durations of generalized tonic-clonic seizures in the MES model.It also significantly prolonged the latencies to generalized myo-clonic seizures in the PTZ model.In the KA model,XNJ showed various efficacies including inhibiting the seizure stages,prolonging the latency to the occurrence of the first seizures or generalized seizures,shortening the seizure durations,decreasing the numbers of generalized seizures.In vitro electrophysiological recordings further verified XNJ directly inhibited both the spontaneous and evoked action potentials of hippocampal pyramidal neurons,but did not influence the excitatory or inhibitory synaptic transmissions.Conclusion:These findings proposed XNJ as an alternative anti-convulsant pharmacotherapy for controlling acute epileptic seizures.展开更多
基金supported by grants from the National Natural Science Foundation of China(U21A20418 and 82173796)the Natural Science Foundation of Zhejiang Province(LD22H310003)the Research Project of Zhejiang Chinese Medical University(2023JKZDZC04).
文摘Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus.It is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy,but still lacks effective treatments.Here,we aimed to test the effects of low-frequency stimulation(LFS)at the subiculum for secondary epileptogenesis in a mouse model.Here,secondary epileptogenesis was simulated at regions both contralateral and ipsilateral to the primary focus by applying successive kindling stimuli.Mice kindled at the right CA3 showed higher seizure susceptibilities at both the contralateral CA3 and the ipsilateral entorhinal cortex and had accelerated kindling processes compared with naive mice.LFS at the ipsilateral subiculum during the primary kindling progress at the right CA3 effectively prevented secondary epileptogenesis at both the contralateral CA3 and the ipsilateral entorhinal cortex,characterized by decreased seizure susceptibilities and a retarded kindling process at those secondary foci.Only application along with the primary epileptogenesis was effective.Notably,the effects of LFS on secondary epileptogenesis were associated with its inhibitory effect at the secondary focus through interfering with the enhancement of synaptic connections between the primary and secondary foci.These results imply that LFS at the subiculum is an effective preventive strategy for extensive secondary epileptogenesis in temporal lobe epilepsy and present the subiculum as a target with potential translational importance.
基金supported by grants from the National Natural Science Foundation of China(82173796)the Natural Science Foundation of Zhejiang Province(LD22H310003).
文摘Acupuncturea representative and historical treatment in traditional Chinese medicine(TCM),has been used to cure diseases for Chinese people in the past centuries.Since the late 1990s,acupuncture has been further accepted worldwide.The World Health Organization(WHO)proposed Clinical Research Specification for acupuncture in 1995 and the US Food and Drug Administration(FDA)approved acupuncture as a complementary and alternative therapy for various kinds of diseases in 1996,with clinical advantages such as convenience and effectiveness[1].Cumulative evidence has proved that acupuncture could produce different degrees of efficacy for treating various kinds of diseases(such as neuropathic pain,migraine,Parkinson's disease et al.)and alleviate symptoms[2-4].However,unlike its evidence-based efficacies.
基金supported by the National Natural Science Foundation of China,No.82173796(to CX)the Research Project of Zhejiang Chinese Medical University,No.2022JKJNTZ13(to XQ).
文摘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.
基金supported by grants from the National Natural Science Foundation of China(Nos.82374064,82173796)the Research Project of Zhejiang Chinese Medical University(2023JKZDZC04)。
文摘Background:The blood-brain barrier(BBB)restricts the effective penetration of anti-seizure drugs(ASDs)into the brain,resulting in unwanted peripheral side effects of ASDs at therapeutic doses.Electroacupuncture(EA)has shown good efficiency in enhancing the drug molecules’permeability of BBB.Objective:We aimed to test the hypothesis that EA could improve the efficacy of ASDs for acute epileptic seizures by increasing their intracerebral concentrations.Methods:Firstly,quantitative analysis of electroacupuncture-mediated alterations in blood-brain barrier per-meability was performed involved two metrics:(1)Evans Blue penetration measured by the in vivo imaging system(IVIS)fluorescence imaging,and(2)brain tissue drug levels analyzed with high-performance liquid chromatography-mass spectrometry(HPLC)following intraperitoneal injection of ASDs,both experiments were performed after EA and intraperitoneal injection.Next,assessment of anti-seizure efficacy in models,as follow:post-electroacupuncture stimulation at GV20 and GV16,therapeutic and sub-doses of ASDs were delivered via intraperitoneal injection.Seizure susceptibility was evaluated using two distinct provocation methods:the clas-sic maximal electroshock tests and the pentylenetetrazol(i.p.)treatments,with seizure intensity being record.Lastly,the safety profile of electroacupuncture was preliminarily evaluated through open field test(OFT)and hot plate experiments.Results:We initially confirmed that EA was capable of enhancing the permeability of the BBB and increasing the intra-cerebral concentration of valproate acid.Then,behavioral experiments confirmed that EA combined with ASD exhibited superior efficacy compared to ASD monotherapy for acute seizures in both models.This enhancing efficacy could be extended to different ASDs with distinct acting mechanisms,including valproate acid,lamotrigine,lacosamide,and levetiracetam.And the electroacupuncture stimulation parameters were confirmed to be safe in mice through comprehensive behavioral evaluation.Conclusion:The results of the present study indicated that EA could improve the therapeutic efficacy of ASDs by enhancing the concentration of drugs in the brain,and provided a blueprint for better anti-seizure management with potential translational significance.
基金This work was financially supported by the Natural Science Foun-dation of Zhejiang Province(LD22H310003)the National Natural Science Foundation of China(82173796)the Research Project of Zhe-jiang Chinese Medical University(2022JKJNTZ13).
文摘Background:Epilepsy is characterized by acute recurrent seizures.The control of seizures is largely hampered by the tolerance to current anti-seizure drugs.Complementary anti-convulsant pharmacotherapies are urgently needed.Objective:Here,we aimed to investigate the anti-convulsant effects of Xingnaojing Injection(XNJ)which is an approved Traditional Chinese Medicine injection on different acute seizure models in mice.Methods:The effects of XNJ were tested on the maximal electroshock(MES),pentylenetetrazol(PTZ)and kainic acid(KA)acute seizure models.Also,whether XNJ can directly inhibit hippocampal neuronal firings were exam-ined by in vitro electrophysiology.Results:XNJ could shorten the durations of generalized tonic-clonic seizures in the MES model.It also significantly prolonged the latencies to generalized myo-clonic seizures in the PTZ model.In the KA model,XNJ showed various efficacies including inhibiting the seizure stages,prolonging the latency to the occurrence of the first seizures or generalized seizures,shortening the seizure durations,decreasing the numbers of generalized seizures.In vitro electrophysiological recordings further verified XNJ directly inhibited both the spontaneous and evoked action potentials of hippocampal pyramidal neurons,but did not influence the excitatory or inhibitory synaptic transmissions.Conclusion:These findings proposed XNJ as an alternative anti-convulsant pharmacotherapy for controlling acute epileptic seizures.
