Perinatal hypoxic-ischemic-encephalopathy significantly contributes to neonatal death and life-long disability such as cerebral palsy. Advances in signal processing and machine learning have provided the research comm...Perinatal hypoxic-ischemic-encephalopathy significantly contributes to neonatal death and life-long disability such as cerebral palsy. Advances in signal processing and machine learning have provided the research community with an opportunity to develop automated real-time identification techniques to detect the signs of hypoxic-ischemic-encephalopathy in larger electroencephalography/amplitude-integrated electroencephalography data sets more easily. This review details the recent achievements, performed by a number of prominent research groups across the world, in the automatic identification and classification of hypoxic-ischemic epileptiform neonatal seizures using advanced signal processing and machine learning techniques. This review also addresses the clinical challenges that current automated techniques face in order to be fully utilized by clinicians, and highlights the importance of upgrading the current clinical bedside sampling frequencies to higher sampling rates in order to provide better hypoxic-ischemic biomarker detection frameworks. Additionally, the article highlights that current clinical automated epileptiform detection strategies for human neonates have been only concerned with seizure detection after the therapeutic latent phase of injury. Whereas recent animal studies have demonstrated that the latent phase of opportunity is critically important for early diagnosis of hypoxic-ischemic-encephalopathy electroencephalography biomarkers and although difficult, detection strategies could utilize biomarkers in the latent phase to also predict the onset of future seizures.展开更多
目的探讨新生儿惊厥患儿神经系统预后及不良结局的危险因素。方法选择2019年12月至2020年11月郑州大学第三附属医院新生儿病房收治的新生儿惊厥患儿进行回顾性研究,根据患儿生存结局、12月龄时智力发育指数(mental development index,M...目的探讨新生儿惊厥患儿神经系统预后及不良结局的危险因素。方法选择2019年12月至2020年11月郑州大学第三附属医院新生儿病房收治的新生儿惊厥患儿进行回顾性研究,根据患儿生存结局、12月龄时智力发育指数(mental development index,MDI)、精神运动发育指数(psychomotor development index,PDI)及惊厥发作情况,将患儿分为不良结局组和正常结局组,分析不良结局的危险因素。结果共纳入75例患儿,不良结局组39例,正常结局组36例;振幅整合脑电图(amplitude-integrated electroencephalogram,aEEG)异常69例,其中轻度异常38例、中度异常23例、重度异常8例,不同aEEG异常程度患儿不良结局发生率及死亡率比较,差异均有统计学意义(P<0.05),aEEG异常程度与不良结局发生率和死亡率均成正相关(r=0.367、0.471,P<0.05)。单因素分析显示,不良结局组患儿绒毛膜羊膜炎、发病日龄≤3 d、5 min Apgar评分≤3分、头颅超声异常、头颅MRI异常及aEEG异常发生率均高于正常结局组,差异有统计学意义(P<0.05);logistic回归分析显示,发病日龄≤3 d(OR=3.988,95%CI 1.376~11.674)、头颅MRI异常(OR=3.296,95%CI 2.383~17.377)及胆红素脑病(OR=3.792,95%CI 2.110~13.216)是新生儿惊厥不良结局的独立危险因素(P<0.05)。结论新生儿惊厥患儿aEEG异常程度越重,不良结局发生率及死亡率越高。发病日龄≤3 d、头颅MRI异常及胆红素脑病是新生儿惊厥患儿不良结局的独立危险因素。展开更多
BACKGROUND： Studies have explored changes in neonatal rat glucocorticoid receptor （GR） expression changes following mature brain injury. OBJECTIVE： To investigate the temporal and special changes of GR during brai...BACKGROUND： Studies have explored changes in neonatal rat glucocorticoid receptor （GR） expression changes following mature brain injury. OBJECTIVE： To investigate the temporal and special changes of GR during brain development in rats with recurrent seizures. DESIGN, TIME AND SE＇n＇ING： A randomized, controlled animal experiment was performed at the Department of Pediatrics, Second Xiangya Hospital of Central South University, from February 2008 to March 2009. MATERIALS： Rabbit anti-rat GR monoclonal antibody was purchased from Santa Cruz Biotechnology, USA; goat anti-rabbit IgG was purchased from Zhongshan Goldenbridge Biotechnology, China. METHODS： A total of 48 Sprague-Dawley rats, 7 days old, were randomly assigned to control and seizure groups, with 24 animals in each group. Seizures were induced by inhalant flurothyl. MAIN OUTCOME MEASURES： Changes in GR protein expression in the rat cerebral cortex were detected by Western blotting analysis and immunohistochemistry. RESULTS： GR expression in the cerebral cortex of control rats significantly increased with aging （P 〈 0.05）, and varied in the frontal lobe, temporal lobe, and parietal lobe. GR was predominantly expressed in the cytoplasm early and rapidly increased in the nuclei. GR protein expression in the cerebral cortex after seizure was lower in the cytoplasm at 15 days and in nuclear protein at 19 days. CONCLUSION： GR expression displayed temporal and spatial changes in brain development. Recurrent seizures in neonatal rats cause abnormal GR expression and might play an important role in developing brain injury.展开更多
Alongside clinical achievements,experiments conducted on animal models (including primate or non-primate) have been effective in the understanding of various pathophysiological aspects of perinatal hypoxic/ ischemic e...Alongside clinical achievements,experiments conducted on animal models (including primate or non-primate) have been effective in the understanding of various pathophysiological aspects of perinatal hypoxic/ ischemic encephalopathy (HIE).Due to the reasonably fair degree of flexibility with experiments,most of the research around HIE in the literature has been largely concerned with the neurodevelopmental outcome or how the frequency and duration of HI seizures could relate to the severity of perinatal brain injury,following HI insult.This survey concentrates on how EEG experimental studies using asphyxiated animal models (in rodents,piglets,sheep and non-human primate monkeys) provide a unique opportunity to examine from the exact time of HI event to help gain insights into HIE where human studies become difficult.展开更多
BACKGROUND： Developmental seizures, which are pathologically characterized by regenerative sprouting of hippocampal mossy fibers, cause long-term damaging effects to synaptic plasticity. Zn^2＋ metabolism has been sh...BACKGROUND： Developmental seizures, which are pathologically characterized by regenerative sprouting of hippocampal mossy fibers, cause long-term damaging effects to synaptic plasticity. Zn^2＋ metabolism has been shown to contribute to the regenerative sprouting of hippocampal mossy fibers Furthermore, zinc transporter-3 （ZnT3） is responsible for Zn^2＋ transport in the hippocampal mossy fiber pathway. OBJECTIVE： To investigate the effects of long-term recurrent neonatal seizures on learning, memory formation and hippocampal ZnT3 expression in rats. DESIGN, TIME AND SETTING： Based on molecular biological research and behavioral examination a randomized, controlled, animal experiment was performed at the Laboratory Animal Center, Peking University Health Science Center, between October 2004 and July 2005. MATERIALS： Flurothyl was purchased from Aldrich Chemical Co., USA. ZnT3 mRNA in situ hybridization kits were provided by Tianjin Haoyang Biological Manufacture Co., Ltd., China. Morris water maze was produced by Shanghai Jiliang Science and Technology Co., Ltd., China. METHODS： Sixty, 6-day old, Wistar rats were randomly divided into three groups： single seizure （n = 21）, recurrent seizure （n = 21, one seizure daily for 6 consecutive days）, and control （n = 18）. Seizures were induced by flurothyl gas inhalation, in the single seizure and recurrent seizure groups. MAIN OUTCOME MEASURES： At postnatal days 12, 46 and 90, rat hippocampal ZnT3 mRNA expression was detected by RT-PCR; at postnatal days 46 and 90, ZnT3 mRNA expression was determined by in situ hybridization; and at postnatal days 41-46 and 85 90, rat spatial learning and memory formation were examined by the Morris water maze test. RESULTS： RT-PCR results revealed that at postnatal day 12, ZnT3 expression was significantly greater in the recurrent seizure group than in the control and single seizure groups, and at day 46, it was also significantly greater in the recurrent seizure group compared with the control group �展开更多
基金supported by the Auckland Medical Research Foundation,No.1117017(to CPU)
文摘Perinatal hypoxic-ischemic-encephalopathy significantly contributes to neonatal death and life-long disability such as cerebral palsy. Advances in signal processing and machine learning have provided the research community with an opportunity to develop automated real-time identification techniques to detect the signs of hypoxic-ischemic-encephalopathy in larger electroencephalography/amplitude-integrated electroencephalography data sets more easily. This review details the recent achievements, performed by a number of prominent research groups across the world, in the automatic identification and classification of hypoxic-ischemic epileptiform neonatal seizures using advanced signal processing and machine learning techniques. This review also addresses the clinical challenges that current automated techniques face in order to be fully utilized by clinicians, and highlights the importance of upgrading the current clinical bedside sampling frequencies to higher sampling rates in order to provide better hypoxic-ischemic biomarker detection frameworks. Additionally, the article highlights that current clinical automated epileptiform detection strategies for human neonates have been only concerned with seizure detection after the therapeutic latent phase of injury. Whereas recent animal studies have demonstrated that the latent phase of opportunity is critically important for early diagnosis of hypoxic-ischemic-encephalopathy electroencephalography biomarkers and although difficult, detection strategies could utilize biomarkers in the latent phase to also predict the onset of future seizures.
文摘目的探讨新生儿惊厥患儿神经系统预后及不良结局的危险因素。方法选择2019年12月至2020年11月郑州大学第三附属医院新生儿病房收治的新生儿惊厥患儿进行回顾性研究,根据患儿生存结局、12月龄时智力发育指数(mental development index,MDI)、精神运动发育指数(psychomotor development index,PDI)及惊厥发作情况,将患儿分为不良结局组和正常结局组,分析不良结局的危险因素。结果共纳入75例患儿,不良结局组39例,正常结局组36例;振幅整合脑电图(amplitude-integrated electroencephalogram,aEEG)异常69例,其中轻度异常38例、中度异常23例、重度异常8例,不同aEEG异常程度患儿不良结局发生率及死亡率比较,差异均有统计学意义(P<0.05),aEEG异常程度与不良结局发生率和死亡率均成正相关(r=0.367、0.471,P<0.05)。单因素分析显示,不良结局组患儿绒毛膜羊膜炎、发病日龄≤3 d、5 min Apgar评分≤3分、头颅超声异常、头颅MRI异常及aEEG异常发生率均高于正常结局组,差异有统计学意义(P<0.05);logistic回归分析显示,发病日龄≤3 d(OR=3.988,95%CI 1.376~11.674)、头颅MRI异常(OR=3.296,95%CI 2.383~17.377)及胆红素脑病(OR=3.792,95%CI 2.110~13.216)是新生儿惊厥不良结局的独立危险因素(P<0.05)。结论新生儿惊厥患儿aEEG异常程度越重,不良结局发生率及死亡率越高。发病日龄≤3 d、头颅MRI异常及胆红素脑病是新生儿惊厥患儿不良结局的独立危险因素。
基金the National Natural Science Foundation of China,No.30400483the Natural Science Foundation of Hunan Province,No.07JJ5020
文摘BACKGROUND： Studies have explored changes in neonatal rat glucocorticoid receptor （GR） expression changes following mature brain injury. OBJECTIVE： To investigate the temporal and special changes of GR during brain development in rats with recurrent seizures. DESIGN, TIME AND SE＇n＇ING： A randomized, controlled animal experiment was performed at the Department of Pediatrics, Second Xiangya Hospital of Central South University, from February 2008 to March 2009. MATERIALS： Rabbit anti-rat GR monoclonal antibody was purchased from Santa Cruz Biotechnology, USA; goat anti-rabbit IgG was purchased from Zhongshan Goldenbridge Biotechnology, China. METHODS： A total of 48 Sprague-Dawley rats, 7 days old, were randomly assigned to control and seizure groups, with 24 animals in each group. Seizures were induced by inhalant flurothyl. MAIN OUTCOME MEASURES： Changes in GR protein expression in the rat cerebral cortex were detected by Western blotting analysis and immunohistochemistry. RESULTS： GR expression in the cerebral cortex of control rats significantly increased with aging （P 〈 0.05）, and varied in the frontal lobe, temporal lobe, and parietal lobe. GR was predominantly expressed in the cytoplasm early and rapidly increased in the nuclei. GR protein expression in the cerebral cortex after seizure was lower in the cytoplasm at 15 days and in nuclear protein at 19 days. CONCLUSION： GR expression displayed temporal and spatial changes in brain development. Recurrent seizures in neonatal rats cause abnormal GR expression and might play an important role in developing brain injury.
基金supported by the Auckland Medical Research Foundation,No.1117017(to CPU)
文摘Alongside clinical achievements,experiments conducted on animal models (including primate or non-primate) have been effective in the understanding of various pathophysiological aspects of perinatal hypoxic/ ischemic encephalopathy (HIE).Due to the reasonably fair degree of flexibility with experiments,most of the research around HIE in the literature has been largely concerned with the neurodevelopmental outcome or how the frequency and duration of HI seizures could relate to the severity of perinatal brain injury,following HI insult.This survey concentrates on how EEG experimental studies using asphyxiated animal models (in rodents,piglets,sheep and non-human primate monkeys) provide a unique opportunity to examine from the exact time of HI event to help gain insights into HIE where human studies become difficult.
基金the National Natural Science Foundation of China,No.30470555, 30870808the Natural Science Foundation of Jiangsu Province of China, No.BK2007509the Natural Science Foundation for Higher Education Institutions in Jiangsu Province, No.07KJB320103
文摘BACKGROUND： Developmental seizures, which are pathologically characterized by regenerative sprouting of hippocampal mossy fibers, cause long-term damaging effects to synaptic plasticity. Zn^2＋ metabolism has been shown to contribute to the regenerative sprouting of hippocampal mossy fibers Furthermore, zinc transporter-3 （ZnT3） is responsible for Zn^2＋ transport in the hippocampal mossy fiber pathway. OBJECTIVE： To investigate the effects of long-term recurrent neonatal seizures on learning, memory formation and hippocampal ZnT3 expression in rats. DESIGN, TIME AND SETTING： Based on molecular biological research and behavioral examination a randomized, controlled, animal experiment was performed at the Laboratory Animal Center, Peking University Health Science Center, between October 2004 and July 2005. MATERIALS： Flurothyl was purchased from Aldrich Chemical Co., USA. ZnT3 mRNA in situ hybridization kits were provided by Tianjin Haoyang Biological Manufacture Co., Ltd., China. Morris water maze was produced by Shanghai Jiliang Science and Technology Co., Ltd., China. METHODS： Sixty, 6-day old, Wistar rats were randomly divided into three groups： single seizure （n = 21）, recurrent seizure （n = 21, one seizure daily for 6 consecutive days）, and control （n = 18）. Seizures were induced by flurothyl gas inhalation, in the single seizure and recurrent seizure groups. MAIN OUTCOME MEASURES： At postnatal days 12, 46 and 90, rat hippocampal ZnT3 mRNA expression was detected by RT-PCR; at postnatal days 46 and 90, ZnT3 mRNA expression was determined by in situ hybridization; and at postnatal days 41-46 and 85 90, rat spatial learning and memory formation were examined by the Morris water maze test. RESULTS： RT-PCR results revealed that at postnatal day 12, ZnT3 expression was significantly greater in the recurrent seizure group than in the control and single seizure groups, and at day 46, it was also significantly greater in the recurrent seizure group compared with the control group �
