Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact...Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely unknown.Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH.In this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery.Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage.Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of PTH.Additionally,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying PTH.Moreover,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH.Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.展开更多
DEAR EDITOR,Cognitive flexibility is crucial for animal survival but is frequently impaired in neuropsychiatric disorders.Although many brain structures and functional networks are involved in cognitive flexibility,th...DEAR EDITOR,Cognitive flexibility is crucial for animal survival but is frequently impaired in neuropsychiatric disorders.Although many brain structures and functional networks are involved in cognitive flexibility,the neural mechanisms underlying cooperation among specific functional networks remain unclear from a global perspective.In this study,[^(18)F]-fluorodeoxyglucose positron emission tomography(FDG-PET)was performed on 19 male tree shrews after four different visual discrimination tasks,including baseline,learning expert(LE),reversal naive(RN),and reversal expert(RE).展开更多
Hypothermia is an important protective strategy against global cerebral ischemia following cardiac arrest.However,the mechanisms of hypothermia underlying the changes in different regions and connections of the brain ...Hypothermia is an important protective strategy against global cerebral ischemia following cardiac arrest.However,the mechanisms of hypothermia underlying the changes in different regions and connections of the brain have not been fully elucidated.This study aims to identify the metabolic nodes and connection integrity of specific brain regions in rats with global cerebral ischemia that are most affected by hypothermia treatment.18F-fluorodeoxyglucose positron emission tomography was used to quantitatively determine glucose metabolism in different brain regions in a rat model of global cerebral ischemia established at 31–33℃.Diffusion tensor imaging was also used to reconstruct and explore the brain connections involved.The results showed that,compared with the model rats established at 37–37.5℃,the rat models of global cerebral ischemia established at 31–33℃had smaller hypometabolic regions in the thalamus and primary sensory areas and sustained no obvious thalamic injury.Hypothermia selectively preserved the integrity of the anterior forebrain mesocircuit,exhibiting protective effects on the brain during the global cerebral ischemia.The study was approved by the Institutional Animal Care and Use Committee at Capital Medical University(approval No.XW-AD318-97-019)on December 15,2019.展开更多
Although CRISPR/Cas9-mediated gene editing is widely applied to mimic human disorders,whether acute manipulation of disease-causing genes in the brain leads to behavioral abnormalities in non-human primates remains to...Although CRISPR/Cas9-mediated gene editing is widely applied to mimic human disorders,whether acute manipulation of disease-causing genes in the brain leads to behavioral abnormalities in non-human primates remains to be determined.Here we induced genetic mutations in MECP2,a critical gene linked to Rett syndrome(RTT)and autism spectrum disorders(ASD),in the hippocampus(DG and CA1–4)of adolescent rhesus monkeys(Macaca mulatta)in vivo via adeno-associated virus(AAV)-delivered Staphylococcus aureus Cas9 with small guide RNAs(sg RNAs)targeting MECP2.In comparison to monkeys injected with AAV-Sa Cas9 alone(n=4),numerous autistic-like behavioral abnormalities were identified in the AAV-Sa Cas9-sg MECP2-injected monkeys(n=7),including social interaction deficits,abnormal sleep patterns,insensitivity to aversive stimuli,abnormal hand motions,and defective social reward behaviors.Furthermore,some aspects of ASD and RTT,such as stereotypic behaviors,did not appear in the MECP2 gene-edited monkeys,suggesting that different brain areas likely contribute to distinct ASD symptoms.This study showed that acute manipulation of disease-causing genes via in vivo gene editing directly led to behavioral changes in adolescent primates,paving the way for the rapid generation of genetically engineered non-human primate models for neurobiological studies and therapeutic development.展开更多
基金supported by the Natural Science Foundation of Guangdong Province,China(2021A1515010897)Discipline Construction Fund of Central People’s Hospital of Zhanjiang(2020A01,2020A02)+1 种基金National Natural Science Foundation of China(31970973,21921004,32271148)Biosecurity Research Project(23SWAQ24)。
文摘Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely unknown.Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH.In this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery.Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage.Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of PTH.Additionally,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying PTH.Moreover,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH.Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.
基金supported by the National Natural Science Foundation of China(11975249,81771923,12175268,32071029,31861143037)China Postdoctoral Science Foundation(2021T140668)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32020000)。
文摘DEAR EDITOR,Cognitive flexibility is crucial for animal survival but is frequently impaired in neuropsychiatric disorders.Although many brain structures and functional networks are involved in cognitive flexibility,the neural mechanisms underlying cooperation among specific functional networks remain unclear from a global perspective.In this study,[^(18)F]-fluorodeoxyglucose positron emission tomography(FDG-PET)was performed on 19 male tree shrews after four different visual discrimination tasks,including baseline,learning expert(LE),reversal naive(RN),and reversal expert(RE).
基金supported by Beijing Municipal Health Commission of China,No.Jing2019-2(to TLW)。
文摘Hypothermia is an important protective strategy against global cerebral ischemia following cardiac arrest.However,the mechanisms of hypothermia underlying the changes in different regions and connections of the brain have not been fully elucidated.This study aims to identify the metabolic nodes and connection integrity of specific brain regions in rats with global cerebral ischemia that are most affected by hypothermia treatment.18F-fluorodeoxyglucose positron emission tomography was used to quantitatively determine glucose metabolism in different brain regions in a rat model of global cerebral ischemia established at 31–33℃.Diffusion tensor imaging was also used to reconstruct and explore the brain connections involved.The results showed that,compared with the model rats established at 37–37.5℃,the rat models of global cerebral ischemia established at 31–33℃had smaller hypometabolic regions in the thalamus and primary sensory areas and sustained no obvious thalamic injury.Hypothermia selectively preserved the integrity of the anterior forebrain mesocircuit,exhibiting protective effects on the brain during the global cerebral ischemia.The study was approved by the Institutional Animal Care and Use Committee at Capital Medical University(approval No.XW-AD318-97-019)on December 15,2019.
基金supported by the Key-Area Research and Development Program of Guangdong Province (2019B03035001)the National Natural Science Foundation of China (81941014, 31625013, 91732302, 81471312, 81771387, 81460352, 81500983, 31700897, 31700910, 31800901, 31700897, 31960178, and 81460352)+7 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences (XDBS32060200)the Shanghai Brain-Intelligence Project from the Science and Technology Commission of the Shanghai Municipality (16JC1420501)the Shanghai Municipal Science and Technology Major Project (2018SHZDZX05)the Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province (2017FB109, 2018FB052, 2018FB053, and 2019FA007)the China Postdoctoral Science Foundation (2018M631105)the CAS ‘‘Light of West China” Programthe National Key R&D Program of China (2018YFA0801403)the Key Scientific and Technological Projects of Guangdong Province (2018B030335001)。
文摘Although CRISPR/Cas9-mediated gene editing is widely applied to mimic human disorders,whether acute manipulation of disease-causing genes in the brain leads to behavioral abnormalities in non-human primates remains to be determined.Here we induced genetic mutations in MECP2,a critical gene linked to Rett syndrome(RTT)and autism spectrum disorders(ASD),in the hippocampus(DG and CA1–4)of adolescent rhesus monkeys(Macaca mulatta)in vivo via adeno-associated virus(AAV)-delivered Staphylococcus aureus Cas9 with small guide RNAs(sg RNAs)targeting MECP2.In comparison to monkeys injected with AAV-Sa Cas9 alone(n=4),numerous autistic-like behavioral abnormalities were identified in the AAV-Sa Cas9-sg MECP2-injected monkeys(n=7),including social interaction deficits,abnormal sleep patterns,insensitivity to aversive stimuli,abnormal hand motions,and defective social reward behaviors.Furthermore,some aspects of ASD and RTT,such as stereotypic behaviors,did not appear in the MECP2 gene-edited monkeys,suggesting that different brain areas likely contribute to distinct ASD symptoms.This study showed that acute manipulation of disease-causing genes via in vivo gene editing directly led to behavioral changes in adolescent primates,paving the way for the rapid generation of genetically engineered non-human primate models for neurobiological studies and therapeutic development.
