Seizures due to cortical dysplasia are notorious for their poor prognosis even with medications and surgery,likely due to the widespread seizure network.Previous studies have primarily focused on the disruption of dys...Seizures due to cortical dysplasia are notorious for their poor prognosis even with medications and surgery,likely due to the widespread seizure network.Previous studies have primarily focused on the disruption of dysplastic lesions,rather than remote regions such as the hippocampus.Here,we first quantified the epileptogenicity of the hippocampus in patients with late-stage cortical dysplasia.We further investigated the cellular substrates leading to the epileptic hippocampus,using multiscale tools including calcium imaging,optogenetics,immunohistochemistry and electrophysiology.For the first time,we revealed the role of hippocampal somatostatin-positive interneurons in cortical dysplasia-related seizures.Somatostatin-positive were recruited during cortical dysplasia-related seizures.Interestingly,optogenetic studies suggested that somatostatin-positive interneurons paradoxically facilitated seizure generalization.By contrast,parvalbumin-positive interneurons retained an inhibitory role as in controls.Electrophysiological recordings and immunohistochemical studies revealed glutamate-mediated excitatory transmission from somatostatin-positive interneurons in the dentate gyrus.Taken together,our study reveals a novel role of excitatory somatostatin-positive neurons in the seizure network and brings new insights into the cellular basis of cortical dysplasia.展开更多
Status epilepticus(SE)is a common fatal neurological disease with high morbidity and mortality,Even if a large proportion of patients might be relieved from anti-seizure medications,sedatives and anesthetics,some stil...Status epilepticus(SE)is a common fatal neurological disease with high morbidity and mortality,Even if a large proportion of patients might be relieved from anti-seizure medications,sedatives and anesthetics,some still remain out of control.The ketogenic dietary(KD)has been proven useful in patients refractory to medications and/or who have failed to respond to surgical intervention.Recently,KD has shown beneficial therapeutic effects in children with SE,but studies in adults have rarely been reported.In this paper,we review the efficacy and utility of KD in adult SE patients and highlight its application for clinical reference and management.展开更多
Status epilepticus （SE） is a life-threatening neurological emergency associated with a high mortality rate. The serotonin 1A （5-HTIA） receptor is a possible target for the treatment of SE, but its role in animal m...Status epilepticus （SE） is a life-threatening neurological emergency associated with a high mortality rate. The serotonin 1A （5-HTIA） receptor is a possible target for the treatment of SE, but its role in animal models and the precise area of brain involved remain controversial. The hippocampus is a candidate site due to its key role in the development of SE and the existence of a high density of 5-HT1A receptors. Therefore, we investigated the effects of subcutaneous and intrahippocampal activation of 5-HT1A receptors in lithium-pilocarpine-induced SE, and tested whether the hippocampus is a true effector site. We developed SE in male Sprague-Dawley rats by giving lithium chloride （LiCI; 3 meq/kg, i.p.） 22-24 h prior to pilocarpine （25 mg/kg, i.p.）, and found that 8-OH-DPAT, a 5-HT1A receptor agonist administered subcutaneously （s.c.） at 0.5 or 1.0 mg/kg 1 h before pilocarpine injection increased the latency to the first epileptiform spikes, the electrographic SE, and the behavioral generalized seizures （GS）, while reducing the total EEG seizure time （P 〈0.01）. The duration of GS was shortened only by 1.0 mg/kg 8-OH-DPAT s.c. （P 〈0.05）. All these effects were inhibited by combined administration of WAY-100635 （1.0 mg/kg, s.c.） （P 〈0.05）, an antagonist of the 5-HT1A receptor, but WAY-100635 alone and low doses of 8-OH- DPAT （0.01 and 0.1 mg/kg） did not alter seizure activity. Furthermore, intrahippocampal 8-OH-DPAT only shortened the GS duration （P 〈0.05）. These findings imply that the 5-HT1A receptor is a promising therapeutic target against the generation and propagation of SE, and hippocampal receptors are involved in reducing the seizure severity.展开更多
Super-refractory status epilepticus(SRSE)is a serious and life-threatening neurological condition.Ketogenic diet(KD)is a diet characterized by high fat,low carbohydrate,and moderate protein.As KD shows effectiveness i...Super-refractory status epilepticus(SRSE)is a serious and life-threatening neurological condition.Ketogenic diet(KD)is a diet characterized by high fat,low carbohydrate,and moderate protein.As KD shows effectiveness in controlling seizures in more than half of SRSE patients,it can be a treatment option for SRSE.Currently,KD treatment for SRSE is based on personal experience and observational evidence has been published.In the context of a lack of a validated guideline,we convened a multicenter expert panel within the China Association Against Epilepsy(CAAE)Ketogenic Diet Commission to work out the Chinese expert recommendations on KD for SRSE.We summarize and discuss the latest clinical practice of KD for SRSE in critical care settings.Recommendations are given on patient selection,the timing of KD,diet implementation,and follow-up.More research data are needed in this area to support better clinical practice.展开更多
基金supported by grants from the National Key R&D Program of China(No.2020YFA0803900)the National Natural Science Foundation of China(82071443,81973298,82173796,82022071,82201607)the Natural Science Foundation of Zhejiang Province(LD22H310003,Q23H090002).
文摘Seizures due to cortical dysplasia are notorious for their poor prognosis even with medications and surgery,likely due to the widespread seizure network.Previous studies have primarily focused on the disruption of dysplastic lesions,rather than remote regions such as the hippocampus.Here,we first quantified the epileptogenicity of the hippocampus in patients with late-stage cortical dysplasia.We further investigated the cellular substrates leading to the epileptic hippocampus,using multiscale tools including calcium imaging,optogenetics,immunohistochemistry and electrophysiology.For the first time,we revealed the role of hippocampal somatostatin-positive interneurons in cortical dysplasia-related seizures.Somatostatin-positive were recruited during cortical dysplasia-related seizures.Interestingly,optogenetic studies suggested that somatostatin-positive interneurons paradoxically facilitated seizure generalization.By contrast,parvalbumin-positive interneurons retained an inhibitory role as in controls.Electrophysiological recordings and immunohistochemical studies revealed glutamate-mediated excitatory transmission from somatostatin-positive interneurons in the dentate gyrus.Taken together,our study reveals a novel role of excitatory somatostatin-positive neurons in the seizure network and brings new insights into the cellular basis of cortical dysplasia.
基金the National Natural Science Foundation of China(82071443).
文摘Status epilepticus(SE)is a common fatal neurological disease with high morbidity and mortality,Even if a large proportion of patients might be relieved from anti-seizure medications,sedatives and anesthetics,some still remain out of control.The ketogenic dietary(KD)has been proven useful in patients refractory to medications and/or who have failed to respond to surgical intervention.Recently,KD has shown beneficial therapeutic effects in children with SE,but studies in adults have rarely been reported.In this paper,we review the efficacy and utility of KD in adult SE patients and highlight its application for clinical reference and management.
基金supported by grants from the National Natural Science Foundation of China (81000556, 81100968, 81171227)the Traditional Chinese Medicine Scientific Research Fund of Zhejiang Province, China (2010ZA069)
文摘Status epilepticus （SE） is a life-threatening neurological emergency associated with a high mortality rate. The serotonin 1A （5-HTIA） receptor is a possible target for the treatment of SE, but its role in animal models and the precise area of brain involved remain controversial. The hippocampus is a candidate site due to its key role in the development of SE and the existence of a high density of 5-HT1A receptors. Therefore, we investigated the effects of subcutaneous and intrahippocampal activation of 5-HT1A receptors in lithium-pilocarpine-induced SE, and tested whether the hippocampus is a true effector site. We developed SE in male Sprague-Dawley rats by giving lithium chloride （LiCI; 3 meq/kg, i.p.） 22-24 h prior to pilocarpine （25 mg/kg, i.p.）, and found that 8-OH-DPAT, a 5-HT1A receptor agonist administered subcutaneously （s.c.） at 0.5 or 1.0 mg/kg 1 h before pilocarpine injection increased the latency to the first epileptiform spikes, the electrographic SE, and the behavioral generalized seizures （GS）, while reducing the total EEG seizure time （P 〈0.01）. The duration of GS was shortened only by 1.0 mg/kg 8-OH-DPAT s.c. （P 〈0.05）. All these effects were inhibited by combined administration of WAY-100635 （1.0 mg/kg, s.c.） （P 〈0.05）, an antagonist of the 5-HT1A receptor, but WAY-100635 alone and low doses of 8-OH- DPAT （0.01 and 0.1 mg/kg） did not alter seizure activity. Furthermore, intrahippocampal 8-OH-DPAT only shortened the GS duration （P 〈0.05）. These findings imply that the 5-HT1A receptor is a promising therapeutic target against the generation and propagation of SE, and hippocampal receptors are involved in reducing the seizure severity.
基金This work was supported by the Horizontal Scientific Research Project of Sichuan University(No.20H0072).
文摘Super-refractory status epilepticus(SRSE)is a serious and life-threatening neurological condition.Ketogenic diet(KD)is a diet characterized by high fat,low carbohydrate,and moderate protein.As KD shows effectiveness in controlling seizures in more than half of SRSE patients,it can be a treatment option for SRSE.Currently,KD treatment for SRSE is based on personal experience and observational evidence has been published.In the context of a lack of a validated guideline,we convened a multicenter expert panel within the China Association Against Epilepsy(CAAE)Ketogenic Diet Commission to work out the Chinese expert recommendations on KD for SRSE.We summarize and discuss the latest clinical practice of KD for SRSE in critical care settings.Recommendations are given on patient selection,the timing of KD,diet implementation,and follow-up.More research data are needed in this area to support better clinical practice.
