OBJECTIVE: To investigate the antiepileptic effects of Chaihushugan decoction(CHSGD) in rats with pentylenetetrazole(PTZ)-induced seizures and to discuss the impact of CHSGD on glutamate metabolism, a hypothesized und...OBJECTIVE: To investigate the antiepileptic effects of Chaihushugan decoction(CHSGD) in rats with pentylenetetrazole(PTZ)-induced seizures and to discuss the impact of CHSGD on glutamate metabolism, a hypothesized underlying mechanism of seizure reduction.METHODS: Fifty Wistar rats were divided randomly into either control(n = 10) or experimental(n = 40)groups. Rats in the control group were administered physiological saline intraperitoneally. A subconvulsive dose of PTZ(35 mg/kg) was administered intraperitoneally to rats in the experimental group to induce seizures. The fully PTZ-kindled rats were then randomly divided into five subgroups(n = 8 each) based on the following treatment categories: physiological saline, VPA(200 mg/kg), CHSGD(2.5 g/kg), CHSGD(5 g/kg), or CHSGD(10 g/kg),administered orally once per day, respectively. On day 28 following initiation of drug treatment, seizures were monitored. The rats were then sacrificed, and hippocampal dissections were performed for subsequent studies.RESULTS: CHSGD significantly prolonged the latency of myoclonic, clonic, and tonic seizures, while decreasing overall seizure rates in the kindled rats.The measured concentrations of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose(2-NBDG) and glutamate were significantly lower in the hippocampi of kindled rats in groups treated with CHSGD compared with those treated with PTZ alone. In addition, CHSGD was found to up-regulate both the expression of glutamate transporter-1(GLT-1) protein and the activity of glutamine synthetase(GS) in the hippocampi of kindled rats.CONCLUSION: These results suggest that CHSGD has antiepileptic effects on PTZ-induced seizures.The results further suggest an increase in glutamate metabolism at the synaptic cleft is a putative underlying mechanism of seizure reduction.展开更多
Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems.The immunopotentiator thymosin alpha-1(Tal)has recently been...Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems.The immunopotentiator thymosin alpha-1(Tal)has recently been reported to have anti-inflammatory and neuroprotective functions in rodents.However,how Tα1 affects inflammatory pain remains unclear.In the present study,intraperitoneal injection of Tal attenuated complete Freund's adjuvant(CFA)-induced pain hypersensitivity,and decreased the up-regulation of pro-inflammatory cytokines(TNF-α,IL-1β,and IL-6)in inflamed skin and the spinal cord.We found that CFA-induced peripheral inflammation evoked strong microglial activation,but the effect was reversed by Tα1.Notably,Tα1 reversed the CFA-induced up-regulation of vesicular glutamate transporter(VGLUT)and down-regulated the vesicular γ-aminobutyric acid transporter(VGAT)in the spinal cord.Taken together,these results suggest that Tα1 plays a therapeutic role in inflammatory pain and in the modulation of microgliainduced pro-inflammatory cytokine production in addition to mediation of VGLUT and VGAT expression in the spinal cord.展开更多
基金Supported by Guangdong Natural Science Foundation(The effects of "Treatment from Gan"on Regulation of A-type Potassium Channels by KChIP/Kv4 in the pathomechanism of Refractory Epilepsy,No.2014A030310052)National Natural Science Foundation of China(Study on Regulation of A-type Potassium Channels by KChIP/Kv4 in the Pathomechanism of Refractory Epilepsy and the Effects of "Treatment from Gan",No.81503564)
文摘OBJECTIVE: To investigate the antiepileptic effects of Chaihushugan decoction(CHSGD) in rats with pentylenetetrazole(PTZ)-induced seizures and to discuss the impact of CHSGD on glutamate metabolism, a hypothesized underlying mechanism of seizure reduction.METHODS: Fifty Wistar rats were divided randomly into either control(n = 10) or experimental(n = 40)groups. Rats in the control group were administered physiological saline intraperitoneally. A subconvulsive dose of PTZ(35 mg/kg) was administered intraperitoneally to rats in the experimental group to induce seizures. The fully PTZ-kindled rats were then randomly divided into five subgroups(n = 8 each) based on the following treatment categories: physiological saline, VPA(200 mg/kg), CHSGD(2.5 g/kg), CHSGD(5 g/kg), or CHSGD(10 g/kg),administered orally once per day, respectively. On day 28 following initiation of drug treatment, seizures were monitored. The rats were then sacrificed, and hippocampal dissections were performed for subsequent studies.RESULTS: CHSGD significantly prolonged the latency of myoclonic, clonic, and tonic seizures, while decreasing overall seizure rates in the kindled rats.The measured concentrations of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose(2-NBDG) and glutamate were significantly lower in the hippocampi of kindled rats in groups treated with CHSGD compared with those treated with PTZ alone. In addition, CHSGD was found to up-regulate both the expression of glutamate transporter-1(GLT-1) protein and the activity of glutamine synthetase(GS) in the hippocampi of kindled rats.CONCLUSION: These results suggest that CHSGD has antiepileptic effects on PTZ-induced seizures.The results further suggest an increase in glutamate metabolism at the synaptic cleft is a putative underlying mechanism of seizure reduction.
基金supported by the Foundation for Distinguished Young Talents in Higher Education of Guangdong Province, China (2016KQNCX019 and 2016KQNCX027)the National Natural Science Foundation of China (31571041)+1 种基金the Guangdong Provincial Department of Education Innovating Strong National Engineering Major Project (2014GKXM031)Guangdong Provincial Universities and Colleges Pearl River Scholar Funded Scheme (2016)
文摘Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems.The immunopotentiator thymosin alpha-1(Tal)has recently been reported to have anti-inflammatory and neuroprotective functions in rodents.However,how Tα1 affects inflammatory pain remains unclear.In the present study,intraperitoneal injection of Tal attenuated complete Freund's adjuvant(CFA)-induced pain hypersensitivity,and decreased the up-regulation of pro-inflammatory cytokines(TNF-α,IL-1β,and IL-6)in inflamed skin and the spinal cord.We found that CFA-induced peripheral inflammation evoked strong microglial activation,but the effect was reversed by Tα1.Notably,Tα1 reversed the CFA-induced up-regulation of vesicular glutamate transporter(VGLUT)and down-regulated the vesicular γ-aminobutyric acid transporter(VGAT)in the spinal cord.Taken together,these results suggest that Tα1 plays a therapeutic role in inflammatory pain and in the modulation of microgliainduced pro-inflammatory cytokine production in addition to mediation of VGLUT and VGAT expression in the spinal cord.
