Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced ra...Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced rat seizure model.A selected panel of long noncoding RNAs(lncRNAs),which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway,was also targeted.Methods:The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers,neurotrophic factors,and relevant lncRNA genes.Rat behavior was assessed using Y-maze test and open field test(OFT).Results:EPCs mitigated seizure associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits,as evidenced by improved performance in the Y-maze test and OFT.EPC treatment reversed the downregulation of the expression of the lncRNAs Evf2,Pnky,Dlx1,APF,HOTAIR,and FLJ11812.EPCs also boosted vascular endothelial growth factor(VEGF)expression.The ameliorative effect achieved by EPCs was comparable to that produced by valproate.Conclusions:These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.展开更多
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
The effects of chloroquine on glial fibrillary acidic protein （GFAP）, proliferation cell nuclear antigen （PCNA） and Cyclin D1 in hippocampus and cerebral cortex of rats with seizures induced by pentylenetetrazole ...The effects of chloroquine on glial fibrillary acidic protein （GFAP）, proliferation cell nuclear antigen （PCNA） and Cyclin D1 in hippocampus and cerebral cortex of rats with seizures induced by pentylenetetrazole （PTZ） were observed in the present study. Forty-eight male adult Sprague-Dawley （SD） rats were randomly divided into control group, chloroquine intervening group, and PTZ group. The behavior and electroencephalogram （EEG） were observed and recorded. GFAP and PCNA were examined with immunohistochemistry. The content of Cyclin D1 in hippocampus and cerebral cortex was inspected with Western blot. The results showed no seizure activity in the control group, severe seizure activity in the PTZ group （Ⅳ - Ⅴ degree）, and slight seizure activity （ Ⅰ -- Ⅲ degree） in the chloroquine intervening group （P〈0.05）. EEG recordings showed no epileptic spikes in the control group, high amplitude with fast frequency in the PTZ group, low amplitude and slow frequency in the chloroquine intervening group. The expression of GFAP and the positive index of PCNA in the PTZ group were higher than those of control group （P 〈0.05 and P〈0.01, respectively）. No differences in GFAP expression and PCNA index were observed between chloroquine intervening and control groups （P〉0.05）. The content of Cyclin D1 in hippocampus and cerebral cortex was significantly higher in the PTZ group than in control and chloroquine intervening groups （P〈 0.05）. Therefore, it is considered that chloroquine, by inhibiting the functions and proliferation of glial cells in the hippocampus and cerebral cortex, can alleviate the seizure activities. These results suggest that chloroquine may be an ideal anticonvulsant in preventing and treating epilepsy.展开更多
Objective: To evaluate the anticonvulsant effect of the essential oil of Myrothamnus moschatus(M. moschatus) in convulsion induced by pentylenetetrazole and picrotoxin in rodent models.Methods: The essential oil of th...Objective: To evaluate the anticonvulsant effect of the essential oil of Myrothamnus moschatus(M. moschatus) in convulsion induced by pentylenetetrazole and picrotoxin in rodent models.Methods: The essential oil of the aerial parts of M. moschatus was extracted by steam distillation. Thereafter, it was injected subcutaneously to rats and mice at escalating doses(0.1–0.8 m L/kg). Ten minutes after drug injection, pentylenetetrazole was injected intraperitoneally to rats and picrotoxin was administered to mice by the same route.Diazepam served as the positive control. Every single animal was placed into transparent cage and observed for convulsive behavior for 30 min by using ordinary security cameras connected to a video recorder. Death occurring for a period of 24 h was also recorded.Results: The essential oil at 0.8 m L/kg completely arrested the pentylenetetrazole-induced convulsion without any sedative effect and delayed its appearance at lower doses, but showed moderate activities on picrotoxin-induced convulsion. For the rats treated with pentylenetetrazole alone, the mortality was 100% within 1 h, but for the rats pre-treated with the essential oil, the mortality was 0%. For the mice treated with picrotoxin, the mortality rate was also 100%, while 20%–100% died in those that had been pre-treated with the oil.Conclusions: The results confirmed at least partly the traditional uses of the smoke of M. moschatus for the management of convulsion, and implied that the essential oil may inhibit the convulsion by GABAergic neuromodulation.展开更多
Objective: To evaluate the protective effect of morin against pentylenetetrazol(PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice(18-22 g) was used to induce convulsions by intraperitoneal(i.p....Objective: To evaluate the protective effect of morin against pentylenetetrazol(PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice(18-22 g) was used to induce convulsions by intraperitoneal(i.p.) administration of PTZ(90 mg/kg). Mice were either pretreated with morin(10, 20 and 40 mg/kg) or vehicle(distilled water, 10 mg/kg) 45 min before PTZ administration. Various behavioral and biochemical parameters were assessed. Results: PTZ administration resulted in significant production(P<0.001) of tonic-clonic conclusion and mortality in mice. PTZ-induced increase in the duration of convulsion, onset of convulsion and mortality was inhibited significantly by morin(20 and 40 mg/kg) administration. The PTZinduced decrease in brain GABA, dopamine and Na+K+ATPase levels and increase in xanthine oxidase activity were inhibited significantly by morin(20 and 40 mg/kg) treatment. The increased levels of malondialdehyde and nitric oxide level were significantly decreased by morin(20 and 40 mg/kg) treatment. Also, reduced levels of superoxide dismutase and glutathione were increased significantly by morin treatment. Conclusions: Results of the present study indicate that morin showed its anti-convulsant effect via modulating the levels of brain GABA, Na^+K^+ATPase, and oxido-nitrosative stress. Thus, morin can be a potential candidate for further clinical evaluations as an anti-epileptic agent.展开更多
Objective:To assess the effect of sericin against pentylenetetrazole(PTZ)kindling epilepsy and its associated comorbidities.Methods:Epilepsy was induced with PTZ at the dose of 30 mg/kg i.p.on alternative days for 25 ...Objective:To assess the effect of sericin against pentylenetetrazole(PTZ)kindling epilepsy and its associated comorbidities.Methods:Epilepsy was induced with PTZ at the dose of 30 mg/kg i.p.on alternative days for 25 days in rats.Sericin was administered orally at the doses of 250,500,and 1000 mg/kg for 35 days.The behavioral activities were performed using an elevated plus maze,forced swim test,and Morris water maze test.A PTZ challenge test was conducted on day 32.On day 35,rats were sacrificed to perform oxidative stress,mitochondrial dysfunction,neuroinflammation,neurotransmitters,GABA-T activity,and histopathological analyses.Results:Sericin at 500 and 1000 mg/kg significantly reduced behavioral changes and neuroinflammatory cytokines,as well as improved oxidative stress,mitochondrial enzyme complex activity,neurotransmitter level,and GABA-T enzymatic activity(P<0.05).Moreover,sericin improved the neuronal survival altered by PTZ kindling in rat hippocampus.Conclusions:Sericin mitigates epilepsy-associated secondary complications possibly by the modulation of mitochondrial enzyme complexes and GABA-T enzymatic activity.展开更多
Objective To examine the protective effects of allopregnanolone against pentylenetetrazol－ induced seizures. Methods The protective effects of allopregnanolone against pentylenetetrazol－ induced seizures were studie...Objective To examine the protective effects of allopregnanolone against pentylenetetrazol－ induced seizures. Methods The protective effects of allopregnanolone against pentylenetetrazol－ induced seizures were studied in C57 mice and SD rats 15 minutes after vehicle or drug intraperitoneal (ip) administration. Results The pretreatment with the allopregnanolone produced a dose－ dependent protective effect against pentylenetetrazol－ induced seizures. The potencies (ED50 values) were 4.7 mg/kg and 9.8 mg/kg for mice and rats, respectively. Conclusion Allopregnanolone has anticonvulsant activity against pentylenetetrazol－ induced seizures in rodents.展开更多
OBJECTIVE: To investigate the effects of antisense glutamic acid decarboxylase (GAD(67)) oligodeoxynucleo-tide (ODN) on behavior, seizure threshold and EEG of hippocampus in the epileptic rats induced by pentylenetetr...OBJECTIVE: To investigate the effects of antisense glutamic acid decarboxylase (GAD(67)) oligodeoxynucleo-tide (ODN) on behavior, seizure threshold and EEG of hippocampus in the epileptic rats induced by pentylenetetrazol (PTZ). METHODS: A model of chronic epilepsy in rats was established by PTZ. The inhibition of GAD(67) mRNA expression in hippocampus was selectively induced by antisense oligodeoxynucleotide of GAD(67). The effect of antisense GAD(67) ODN on behavior, seizure threshold and EEG recording of kindled rats was examined. RESULTS: Antisense GAD(67) ODN could inhibit the expression of GAD(67) mRNA and the concentration of GABA. It also could significantly shorten the latencies of seizure and increase the level of seizure and the frequency of epileptiform discharges. CONCLUSION: The gene of GAD(67) may be an anti-seizure gene, which might inhibit epileptiform discharge. The treatment of epilepsy by GAD(67) gene will have a bright future.展开更多
Background Histamine H3 receptor antagonists have been considered as potential drugs to treat central nervous system diseases. However, whether these drugs can inhibit epileptogenesis remains unclear. This study aimed...Background Histamine H3 receptor antagonists have been considered as potential drugs to treat central nervous system diseases. However, whether these drugs can inhibit epileptogenesis remains unclear. This study aimed to investigate the effects of thioperamide, a selective and potent histamine H3 receptor antagonist, on the seizure development and memory impairment induced by pentylenetetrazole （PTZ）-kindling epilepsy in rats. Methods Chemical kindling was elicited by repeated intraperitoneal （ip） injections of a subconvulsant dose of PTZ （35 mg/kg） once every 48 hours for 12 times, and seizure activity of kindling was recorded for 30 minutes. Control rats were ip injected with saline instead of PTZ. Morris water maze was used to evaluate the spatial memory. Phosphorylated cyclic adenosine monophosphate response element binding protein （p-CREB） was tested by Western blotting in hippocampus. Results Intracerebroventricular （icv） injections with thioperamide （10 μg, 20 μg） 30 minutes before every PTZ injections, significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages. PTZ-kindling seizures led to the impairment of spatial memory in rats, and thioperamide ameliorated the impairment of spatial learning and memory. Compared to non-kindling rats, there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats, which was reversed by thioperamide. Conclusions Thioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats. The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.展开更多
BACKGROUND Epilepsy impacts millions of people,with many not responding to existing treatments.Some evidence links neuroinflammatory processes to epilepsy.Statins exhibit anti-inflammatory and neuroprotective properti...BACKGROUND Epilepsy impacts millions of people,with many not responding to existing treatments.Some evidence links neuroinflammatory processes to epilepsy.Statins exhibit anti-inflammatory and neuroprotective properties,potentially offering antiepileptic effects.AIM To evaluate the anticonvulsant effects of rosuvastatin in animal models of epilepsy.METHODS Ninety-six albino mice were divided into 16 groups.In the maximal electroshock seizure(MES)model,eight groups received intraperitoneal vehicle,carbama-zepine,rosuvastatin,or a combination.Outcomes measured included seizure protection[tonic hind limb extension(THLE)],duration of THLE,seizure duration,and mortality.In the pentylenetetrazol(PTZ)model,eight groups were pretreated with vehicle,valproate,rosuvastatin,or a combination,with outcomes measured as seizure latency,seizure duration,and mortality.RESULTS In the MES model,rosuvastatin exhibited protection against THLE in a small percentage of mice.Rosuvastatin shortens the duration of THLE in a dose-dependent manner.However,none of these were statistically significant com-pared to the control group.The combination of rosuvastatin 10 mg/kg with carbamazepine 4 mg/kg resulted in a significant reduction in seizure duration compared to the control group,better than carbamazepine alone at 4 mg/kg and 6 mg/kg.In the PTZ model,rosuvastatin alone showed no significant effects on latency,duration of seizure,or mortality.However,rosuvastatin 10 mg/kg combined with valproate 100 mg/kg significantly delayed the onset of seizures,seizure duration and mortality percentage,better than valproate alone at 100 mg/kg.CONCLUSION Rosuvastatin enhanced the anticonvulsant effects of carbamazepine and valproate.Further studies are required to explore the antiepileptic potential of rosuvastatin at various doses,durations,dosage forms,routes and models.展开更多
基金Open access funding provided by The Science,Technology&Innovation Funding Authority(STDF)in coop eration with The Egyptian Knowledge Bank(EKB).
文摘Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced rat seizure model.A selected panel of long noncoding RNAs(lncRNAs),which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway,was also targeted.Methods:The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers,neurotrophic factors,and relevant lncRNA genes.Rat behavior was assessed using Y-maze test and open field test(OFT).Results:EPCs mitigated seizure associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits,as evidenced by improved performance in the Y-maze test and OFT.EPC treatment reversed the downregulation of the expression of the lncRNAs Evf2,Pnky,Dlx1,APF,HOTAIR,and FLJ11812.EPCs also boosted vascular endothelial growth factor(VEGF)expression.The ameliorative effect achieved by EPCs was comparable to that produced by valproate.Conclusions:These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.
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.
文摘The effects of chloroquine on glial fibrillary acidic protein （GFAP）, proliferation cell nuclear antigen （PCNA） and Cyclin D1 in hippocampus and cerebral cortex of rats with seizures induced by pentylenetetrazole （PTZ） were observed in the present study. Forty-eight male adult Sprague-Dawley （SD） rats were randomly divided into control group, chloroquine intervening group, and PTZ group. The behavior and electroencephalogram （EEG） were observed and recorded. GFAP and PCNA were examined with immunohistochemistry. The content of Cyclin D1 in hippocampus and cerebral cortex was inspected with Western blot. The results showed no seizure activity in the control group, severe seizure activity in the PTZ group （Ⅳ - Ⅴ degree）, and slight seizure activity （ Ⅰ -- Ⅲ degree） in the chloroquine intervening group （P〈0.05）. EEG recordings showed no epileptic spikes in the control group, high amplitude with fast frequency in the PTZ group, low amplitude and slow frequency in the chloroquine intervening group. The expression of GFAP and the positive index of PCNA in the PTZ group were higher than those of control group （P 〈0.05 and P〈0.01, respectively）. No differences in GFAP expression and PCNA index were observed between chloroquine intervening and control groups （P〉0.05）. The content of Cyclin D1 in hippocampus and cerebral cortex was significantly higher in the PTZ group than in control and chloroquine intervening groups （P〈 0.05）. Therefore, it is considered that chloroquine, by inhibiting the functions and proliferation of glial cells in the hippocampus and cerebral cortex, can alleviate the seizure activities. These results suggest that chloroquine may be an ideal anticonvulsant in preventing and treating epilepsy.
基金Supported by the University Research Fund 2014/2015 of the University of Camerino under the grant number FPI000044
文摘Objective: To evaluate the anticonvulsant effect of the essential oil of Myrothamnus moschatus(M. moschatus) in convulsion induced by pentylenetetrazole and picrotoxin in rodent models.Methods: The essential oil of the aerial parts of M. moschatus was extracted by steam distillation. Thereafter, it was injected subcutaneously to rats and mice at escalating doses(0.1–0.8 m L/kg). Ten minutes after drug injection, pentylenetetrazole was injected intraperitoneally to rats and picrotoxin was administered to mice by the same route.Diazepam served as the positive control. Every single animal was placed into transparent cage and observed for convulsive behavior for 30 min by using ordinary security cameras connected to a video recorder. Death occurring for a period of 24 h was also recorded.Results: The essential oil at 0.8 m L/kg completely arrested the pentylenetetrazole-induced convulsion without any sedative effect and delayed its appearance at lower doses, but showed moderate activities on picrotoxin-induced convulsion. For the rats treated with pentylenetetrazole alone, the mortality was 100% within 1 h, but for the rats pre-treated with the essential oil, the mortality was 0%. For the mice treated with picrotoxin, the mortality rate was also 100%, while 20%–100% died in those that had been pre-treated with the oil.Conclusions: The results confirmed at least partly the traditional uses of the smoke of M. moschatus for the management of convulsion, and implied that the essential oil may inhibit the convulsion by GABAergic neuromodulation.
文摘Objective: To evaluate the protective effect of morin against pentylenetetrazol(PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice(18-22 g) was used to induce convulsions by intraperitoneal(i.p.) administration of PTZ(90 mg/kg). Mice were either pretreated with morin(10, 20 and 40 mg/kg) or vehicle(distilled water, 10 mg/kg) 45 min before PTZ administration. Various behavioral and biochemical parameters were assessed. Results: PTZ administration resulted in significant production(P<0.001) of tonic-clonic conclusion and mortality in mice. PTZ-induced increase in the duration of convulsion, onset of convulsion and mortality was inhibited significantly by morin(20 and 40 mg/kg) administration. The PTZinduced decrease in brain GABA, dopamine and Na+K+ATPase levels and increase in xanthine oxidase activity were inhibited significantly by morin(20 and 40 mg/kg) treatment. The increased levels of malondialdehyde and nitric oxide level were significantly decreased by morin(20 and 40 mg/kg) treatment. Also, reduced levels of superoxide dismutase and glutathione were increased significantly by morin treatment. Conclusions: Results of the present study indicate that morin showed its anti-convulsant effect via modulating the levels of brain GABA, Na^+K^+ATPase, and oxido-nitrosative stress. Thus, morin can be a potential candidate for further clinical evaluations as an anti-epileptic agent.
文摘Objective:To assess the effect of sericin against pentylenetetrazole(PTZ)kindling epilepsy and its associated comorbidities.Methods:Epilepsy was induced with PTZ at the dose of 30 mg/kg i.p.on alternative days for 25 days in rats.Sericin was administered orally at the doses of 250,500,and 1000 mg/kg for 35 days.The behavioral activities were performed using an elevated plus maze,forced swim test,and Morris water maze test.A PTZ challenge test was conducted on day 32.On day 35,rats were sacrificed to perform oxidative stress,mitochondrial dysfunction,neuroinflammation,neurotransmitters,GABA-T activity,and histopathological analyses.Results:Sericin at 500 and 1000 mg/kg significantly reduced behavioral changes and neuroinflammatory cytokines,as well as improved oxidative stress,mitochondrial enzyme complex activity,neurotransmitter level,and GABA-T enzymatic activity(P<0.05).Moreover,sericin improved the neuronal survival altered by PTZ kindling in rat hippocampus.Conclusions:Sericin mitigates epilepsy-associated secondary complications possibly by the modulation of mitochondrial enzyme complexes and GABA-T enzymatic activity.
文摘Objective To examine the protective effects of allopregnanolone against pentylenetetrazol－ induced seizures. Methods The protective effects of allopregnanolone against pentylenetetrazol－ induced seizures were studied in C57 mice and SD rats 15 minutes after vehicle or drug intraperitoneal (ip) administration. Results The pretreatment with the allopregnanolone produced a dose－ dependent protective effect against pentylenetetrazol－ induced seizures. The potencies (ED50 values) were 4.7 mg/kg and 9.8 mg/kg for mice and rats, respectively. Conclusion Allopregnanolone has anticonvulsant activity against pentylenetetrazol－ induced seizures in rodents.
基金supported by the National Nature Science Foundation of China(No．39700047)．
文摘OBJECTIVE: To investigate the effects of antisense glutamic acid decarboxylase (GAD(67)) oligodeoxynucleo-tide (ODN) on behavior, seizure threshold and EEG of hippocampus in the epileptic rats induced by pentylenetetrazol (PTZ). METHODS: A model of chronic epilepsy in rats was established by PTZ. The inhibition of GAD(67) mRNA expression in hippocampus was selectively induced by antisense oligodeoxynucleotide of GAD(67). The effect of antisense GAD(67) ODN on behavior, seizure threshold and EEG recording of kindled rats was examined. RESULTS: Antisense GAD(67) ODN could inhibit the expression of GAD(67) mRNA and the concentration of GABA. It also could significantly shorten the latencies of seizure and increase the level of seizure and the frequency of epileptiform discharges. CONCLUSION: The gene of GAD(67) may be an anti-seizure gene, which might inhibit epileptiform discharge. The treatment of epilepsy by GAD(67) gene will have a bright future.
基金This study was supported by grants from the Natural Science Foundation of Zhejiang Province （No. Y2090184） and the Project of Chinese Traditional Medicine of Zhejiang Province （No. 2006Y005）.
文摘Background Histamine H3 receptor antagonists have been considered as potential drugs to treat central nervous system diseases. However, whether these drugs can inhibit epileptogenesis remains unclear. This study aimed to investigate the effects of thioperamide, a selective and potent histamine H3 receptor antagonist, on the seizure development and memory impairment induced by pentylenetetrazole （PTZ）-kindling epilepsy in rats. Methods Chemical kindling was elicited by repeated intraperitoneal （ip） injections of a subconvulsant dose of PTZ （35 mg/kg） once every 48 hours for 12 times, and seizure activity of kindling was recorded for 30 minutes. Control rats were ip injected with saline instead of PTZ. Morris water maze was used to evaluate the spatial memory. Phosphorylated cyclic adenosine monophosphate response element binding protein （p-CREB） was tested by Western blotting in hippocampus. Results Intracerebroventricular （icv） injections with thioperamide （10 μg, 20 μg） 30 minutes before every PTZ injections, significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages. PTZ-kindling seizures led to the impairment of spatial memory in rats, and thioperamide ameliorated the impairment of spatial learning and memory. Compared to non-kindling rats, there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats, which was reversed by thioperamide. Conclusions Thioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats. The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.
文摘BACKGROUND Epilepsy impacts millions of people,with many not responding to existing treatments.Some evidence links neuroinflammatory processes to epilepsy.Statins exhibit anti-inflammatory and neuroprotective properties,potentially offering antiepileptic effects.AIM To evaluate the anticonvulsant effects of rosuvastatin in animal models of epilepsy.METHODS Ninety-six albino mice were divided into 16 groups.In the maximal electroshock seizure(MES)model,eight groups received intraperitoneal vehicle,carbama-zepine,rosuvastatin,or a combination.Outcomes measured included seizure protection[tonic hind limb extension(THLE)],duration of THLE,seizure duration,and mortality.In the pentylenetetrazol(PTZ)model,eight groups were pretreated with vehicle,valproate,rosuvastatin,or a combination,with outcomes measured as seizure latency,seizure duration,and mortality.RESULTS In the MES model,rosuvastatin exhibited protection against THLE in a small percentage of mice.Rosuvastatin shortens the duration of THLE in a dose-dependent manner.However,none of these were statistically significant com-pared to the control group.The combination of rosuvastatin 10 mg/kg with carbamazepine 4 mg/kg resulted in a significant reduction in seizure duration compared to the control group,better than carbamazepine alone at 4 mg/kg and 6 mg/kg.In the PTZ model,rosuvastatin alone showed no significant effects on latency,duration of seizure,or mortality.However,rosuvastatin 10 mg/kg combined with valproate 100 mg/kg significantly delayed the onset of seizures,seizure duration and mortality percentage,better than valproate alone at 100 mg/kg.CONCLUSION Rosuvastatin enhanced the anticonvulsant effects of carbamazepine and valproate.Further studies are required to explore the antiepileptic potential of rosuvastatin at various doses,durations,dosage forms,routes and models.
