Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted...Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors.Several genes have been implicated in the pathogenesis of ASD,most of them are involved in neuronal synaptogenesis.A number of environmental factors and associated conditions such as gastrointestinal(GI)abnormalities and immune imbalance have been linked to the pathophysiology of ASD.According to the March 2012 report released by United States Centers for Disease Control and Prevention,the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms.Although there is a strong genetic base for the disease,several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem.Many children suffering from ASD have GI problems such as abdominal pain,chronic diarrhea,constipation,vomiting,gastroesophageal reflux,and intestinal infections.A number of studies focusing on the intestinal mucosa,its permeability,abnormal gut development,leaky gut,and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas.GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children.Maternal infection or autoimmune diseases have been suspected.Activation of the immune system during early development may have deleterious effect on various organs including the nervous system.In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.展开更多
Dexamethasone has been widely used after various neurosurgical procedures due to its anti-inflammatory property and the abilities to restore vascular permeability,inhibit free radicals,and reduce cerebrospinal fluid p...Dexamethasone has been widely used after various neurosurgical procedures due to its anti-inflammatory property and the abilities to restore vascular permeability,inhibit free radicals,and reduce cerebrospinal fluid production.According to the latest guidelines for the treatment of traumatic brain injury in the United States,high-dose glucocorticoids cause neurological damage.To investigate the reason why high-dose glucocorticoids after traumatic brain injury exhibit harmful effect,rat controlled cortical impact models of traumatic brain injury were established.At 1 hour and 2 days after surgery,rat models were intraperitoneally administered dexamethasone 10 mg/kg.The results revealed that 31 proteins were significantly upregulated and 12 proteins were significantly downregulated in rat models of traumatic brain injury after dexamethasone treatment.The Ingenuity Pathway Analysis results showed that differentially expressed proteins were enriched in the mitochondrial dysfunction pathway and synaptogenesis signaling pathway.Western blot analysis and immunohistochemistry results showed that Ndufv2,Maob and Gria3 expression and positive cell count in the dexamethasone-treated group were significantly greater than those in the model group.These findings suggest that dexamethasone may promote a compensatory increase in complex I subunits(Ndufs2 and Ndufv2),increase the expression of mitochondrial enzyme Maob,and upregulate synaptic-transmission-related protein Gria3.These changes may be caused by nerve injury after traumatic brain injury treatment by dexamethasone.The study was approved by Institutional Ethics Committee of Beijing Neurosurgical Institute(approval No.201802001)on June 6,2018.展开更多
Background Electrocardiographic （ECG） changes occurring during the course of acute brain injury （ABI） have been described frequently, but their significances remain uncertain. The present study was designed to inv...Background Electrocardiographic （ECG） changes occurring during the course of acute brain injury （ABI） have been described frequently, but their significances remain uncertain. The present study was designed to investigate the relation of ECG abnormalities to outcome in the patients with ABI. Methods We performed a retrospective, observational study on the ABI patients admitted to the Department of Neurosurgery of the Beijing Tiantan Hospital between December 2005 and December 2007. All the patients accepted 12-lead electrocardiographic examination within 24 hours after injury, then divided into three groups according to the Glasgow coma score （GCS）. In-hospital mortality and one-month outcome assessed by the Glasgow outcome score （GOS） were investigated. Results Of 335 ABI patients （mean ages 32.4 years）, 246 patients （73.4%） had abnormal ECGs. The most common abnormality was ST-T changes （41.5%）, followed by sinus tachycardia （23.6%）. ECG changes had a significant association with the severity and outcome. Logistic regression analysis showed the presence of ST-T changes （OR 2.587, 95%C/1.009 to 6.629, P=0.048） and QT dispersion prolongation （OR 4.656, 95%C/1.956 to 11.082, P=0.001） significantly associated with short outcomes. Conclusions ABI can lead to myocardial damage and ECG changes had a significant association with the severity. ST-T changes and QT dispersion prolongation were the independent prognosis factors for the negative outcome of ABI patients.展开更多
Blast-induced mild traumatic brain injury（m TBI） is of particular concern among military personnel due to exposure to blast energy during military training and combat.The impact of primary low-intensity blast mediat...Blast-induced mild traumatic brain injury（m TBI） is of particular concern among military personnel due to exposure to blast energy during military training and combat.The impact of primary low-intensity blast mediated pathophysiology upon later neurobehavioral disorders has been controversial.Developing a military preclinical blast model to simulate the pathophysiology of human blast injury is an important first step.This article provides an overview of primary blast effects and perspectives of our recent studies demonstrating ultrastructural changes in the brain and behavioral disorders resulting from open-field blast exposures up to 46.6 k Pa using a murine model.The model is scalable and permits exposure to varying magnitudes of primary blast injuries by placing animals at different distances from the blast center or by changing the amount of C4 charge.We here review the implications and future applications and directions of using this animal model to uncover the underlying mechanisms related to primary blast injury.Overall,these studies offer the prospect of enhanced understanding of the pathogenesis of primary low-intensity blast-induced TBI and insights for prevention,diagnosis and treatment of blast induced TBI,particularly m TBI/concussion related to current combat exposures.展开更多
One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a tradi...One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 （34% of 86）; the total number of abnormal perfusion foci decreased by 52 （36%） and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.展开更多
To the Editor: Non-arteritic anterior ischemic optic neuropathy (NAION), characterized by a sudden onset of unilateral painless visual loss and a swollen optic disc, is the most common form of acute optic neuropathy i...To the Editor: Non-arteritic anterior ischemic optic neuropathy (NAION), characterized by a sudden onset of unilateral painless visual loss and a swollen optic disc, is the most common form of acute optic neuropathy in patients over 50 years of age.[1] The pathogenesis of NAION remains unclear, but most histopathological studies support the concept of vasculopathic occlusion in the region of the short posterior ciliary arteries.[2] Functional magnetic resonance imaging (fMRI) is one of the most widely used non-invasive techniques for measuring brain function over time in vivo. To the best of our knowledge, only one study has investigated the effects of stimulating the affected eye in the extra-visual areas in NAION in humans.[3]However, this previous study only examined task-state fMRI, and lacked a measure of resting-state fMRI (rs-fMRI). Thus, it remains unclear whether regional spontaneous brain changes are limited to the visual system.展开更多
Schizophrenia(SZ)is one of the most common mental diseases.Its main characteristics are abnormal social behavior and inability to correctly understand real things.In recent years,the magnetic resonance imaging(MRI)tec...Schizophrenia(SZ)is one of the most common mental diseases.Its main characteristics are abnormal social behavior and inability to correctly understand real things.In recent years,the magnetic resonance imaging(MRI)technique has been popularly utilized to study SZ.However,it is still a great challenge to reveal the essential information contained in the MRI data.In this paper,we proposed a biomarker selection approach based on the multiple hypothesis testing techniques to explore the difference between SZ and healthy controls by using both functional and structural MRI data,in which biomarkers represent both abnormal brain functional connectivity and abnormal brain regions.By implementing the biomarker selection approach,six abnormal brain regions and twenty-three abnormal functional connectivity in the brains of SZ are explored.It is discovered that compared with healthy controls,the significantly reduced gray matter volumes are mainly distributed in the limbic lobe and the basal ganglia,and the significantly increased gray matter volumes are distributed in the frontal gyrus.Meanwhile,it is revealed that the significantly strengthened connections are those between the middle frontal gyrus and the superior occipital gyrus,the superior occipital gyrus and the middle occipital gyrus as well as the middle occipital gyrus and the fusiform gyrus,and the rest connections are significantly weakened.展开更多
文摘Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors.Several genes have been implicated in the pathogenesis of ASD,most of them are involved in neuronal synaptogenesis.A number of environmental factors and associated conditions such as gastrointestinal(GI)abnormalities and immune imbalance have been linked to the pathophysiology of ASD.According to the March 2012 report released by United States Centers for Disease Control and Prevention,the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms.Although there is a strong genetic base for the disease,several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem.Many children suffering from ASD have GI problems such as abdominal pain,chronic diarrhea,constipation,vomiting,gastroesophageal reflux,and intestinal infections.A number of studies focusing on the intestinal mucosa,its permeability,abnormal gut development,leaky gut,and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas.GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children.Maternal infection or autoimmune diseases have been suspected.Activation of the immune system during early development may have deleterious effect on various organs including the nervous system.In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.
基金This study was supported by the National Natural Science Foundation of China,No.81771327(to BYL)the Platform Construction of Basic Research and Clinical Translation of Nervous System Injury,China,No.PXM2020_026280_000002(to BYL)the Scientific Research and Cultivation Fund of the Beijing Neurosurgical Institute,China,No.2020002(to FN).
文摘Dexamethasone has been widely used after various neurosurgical procedures due to its anti-inflammatory property and the abilities to restore vascular permeability,inhibit free radicals,and reduce cerebrospinal fluid production.According to the latest guidelines for the treatment of traumatic brain injury in the United States,high-dose glucocorticoids cause neurological damage.To investigate the reason why high-dose glucocorticoids after traumatic brain injury exhibit harmful effect,rat controlled cortical impact models of traumatic brain injury were established.At 1 hour and 2 days after surgery,rat models were intraperitoneally administered dexamethasone 10 mg/kg.The results revealed that 31 proteins were significantly upregulated and 12 proteins were significantly downregulated in rat models of traumatic brain injury after dexamethasone treatment.The Ingenuity Pathway Analysis results showed that differentially expressed proteins were enriched in the mitochondrial dysfunction pathway and synaptogenesis signaling pathway.Western blot analysis and immunohistochemistry results showed that Ndufv2,Maob and Gria3 expression and positive cell count in the dexamethasone-treated group were significantly greater than those in the model group.These findings suggest that dexamethasone may promote a compensatory increase in complex I subunits(Ndufs2 and Ndufv2),increase the expression of mitochondrial enzyme Maob,and upregulate synaptic-transmission-related protein Gria3.These changes may be caused by nerve injury after traumatic brain injury treatment by dexamethasone.The study was approved by Institutional Ethics Committee of Beijing Neurosurgical Institute(approval No.201802001)on June 6,2018.
基金This study was supported by the National Natural Science Foundation of China （No. C03030201）
文摘Background Electrocardiographic （ECG） changes occurring during the course of acute brain injury （ABI） have been described frequently, but their significances remain uncertain. The present study was designed to investigate the relation of ECG abnormalities to outcome in the patients with ABI. Methods We performed a retrospective, observational study on the ABI patients admitted to the Department of Neurosurgery of the Beijing Tiantan Hospital between December 2005 and December 2007. All the patients accepted 12-lead electrocardiographic examination within 24 hours after injury, then divided into three groups according to the Glasgow coma score （GCS）. In-hospital mortality and one-month outcome assessed by the Glasgow outcome score （GOS） were investigated. Results Of 335 ABI patients （mean ages 32.4 years）, 246 patients （73.4%） had abnormal ECGs. The most common abnormality was ST-T changes （41.5%）, followed by sinus tachycardia （23.6%）. ECG changes had a significant association with the severity and outcome. Logistic regression analysis showed the presence of ST-T changes （OR 2.587, 95%C/1.009 to 6.629, P=0.048） and QT dispersion prolongation （OR 4.656, 95%C/1.956 to 11.082, P=0.001） significantly associated with short outcomes. Conclusions ABI can lead to myocardial damage and ECG changes had a significant association with the severity. ST-T changes and QT dispersion prolongation were the independent prognosis factors for the negative outcome of ABI patients.
基金possible by funding from the DoD Congressionally Directed Medical Research Programs(CDMRP)for the Peer Reviewed Alzheimer’s Research Program Convergence Science Research Award(PRARP-CSRAAZ140109)the research funds of the University of Missouri(to ZG)
文摘Blast-induced mild traumatic brain injury（m TBI） is of particular concern among military personnel due to exposure to blast energy during military training and combat.The impact of primary low-intensity blast mediated pathophysiology upon later neurobehavioral disorders has been controversial.Developing a military preclinical blast model to simulate the pathophysiology of human blast injury is an important first step.This article provides an overview of primary blast effects and perspectives of our recent studies demonstrating ultrastructural changes in the brain and behavioral disorders resulting from open-field blast exposures up to 46.6 k Pa using a murine model.The model is scalable and permits exposure to varying magnitudes of primary blast injuries by placing animals at different distances from the blast center or by changing the amount of C4 charge.We here review the implications and future applications and directions of using this animal model to uncover the underlying mechanisms related to primary blast injury.Overall,these studies offer the prospect of enhanced understanding of the pathogenesis of primary low-intensity blast-induced TBI and insights for prevention,diagnosis and treatment of blast induced TBI,particularly m TBI/concussion related to current combat exposures.
基金funded by the Key Project of Gansu Province, No.2GS054-A43-014-19
文摘One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 （34% of 86）; the total number of abnormal perfusion foci decreased by 52 （36%） and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.
文摘To the Editor: Non-arteritic anterior ischemic optic neuropathy (NAION), characterized by a sudden onset of unilateral painless visual loss and a swollen optic disc, is the most common form of acute optic neuropathy in patients over 50 years of age.[1] The pathogenesis of NAION remains unclear, but most histopathological studies support the concept of vasculopathic occlusion in the region of the short posterior ciliary arteries.[2] Functional magnetic resonance imaging (fMRI) is one of the most widely used non-invasive techniques for measuring brain function over time in vivo. To the best of our knowledge, only one study has investigated the effects of stimulating the affected eye in the extra-visual areas in NAION in humans.[3]However, this previous study only examined task-state fMRI, and lacked a measure of resting-state fMRI (rs-fMRI). Thus, it remains unclear whether regional spontaneous brain changes are limited to the visual system.
基金This work was supported by NSFC(No.11471006 and No.81601456),Science and Technology Innovation Plan of Xi’an(No.2019421315KYPT004JC006)and the HPC Platform,Xi’an Jiaotong University.
文摘Schizophrenia(SZ)is one of the most common mental diseases.Its main characteristics are abnormal social behavior and inability to correctly understand real things.In recent years,the magnetic resonance imaging(MRI)technique has been popularly utilized to study SZ.However,it is still a great challenge to reveal the essential information contained in the MRI data.In this paper,we proposed a biomarker selection approach based on the multiple hypothesis testing techniques to explore the difference between SZ and healthy controls by using both functional and structural MRI data,in which biomarkers represent both abnormal brain functional connectivity and abnormal brain regions.By implementing the biomarker selection approach,six abnormal brain regions and twenty-three abnormal functional connectivity in the brains of SZ are explored.It is discovered that compared with healthy controls,the significantly reduced gray matter volumes are mainly distributed in the limbic lobe and the basal ganglia,and the significantly increased gray matter volumes are distributed in the frontal gyrus.Meanwhile,it is revealed that the significantly strengthened connections are those between the middle frontal gyrus and the superior occipital gyrus,the superior occipital gyrus and the middle occipital gyrus as well as the middle occipital gyrus and the fusiform gyrus,and the rest connections are significantly weakened.
