Issa O Yusuf, Webb Camille, Paul R Thompson, Zuoshang Xu
Protein citrullination (PC) is a posttranslational modification (PTM) that converts a peptidyl arginine into a peptidyl citrulline. Aberrant PC is a hallmark of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, prion disease, and multiple sclerosis. Common among these diseases is a dramatic increase of PC in reactive astrocytes. Some citrullinated proteins have been identified. The most prominent are astrocytic cytoskeletal proteins such as GFAP and vimentin, and myelin protein MBP. Recent investigation in ALS has revealed new changes, including a decreased PC in neurons and an association of PC with myelin protein aggregates. These findings suggest that PC contributes to protein aggregation, neuronal dysfunction, neuroinflammation, and axonal degeneration. However, how PC impact neurodegeneration remains to be understood. Further studies are needed to understand a range of questions, from how PC modulates individual protein functions to its impact on diseases. Because of the PC's robust changes in neurodegenerative diseases, there are also prospects that this PTM may be harnessed as biomarkers, and modulation of this PTM may be an avenue for therapy. In this review, we summarize the current understanding of PC in ALS and other neurodegenerative diseases, the investigative methods for PC, and PC's potential as a biomarker and a therapeutic target.
{"title":"Protein Citrullination in Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases.","authors":"Issa O Yusuf, Webb Camille, Paul R Thompson, Zuoshang Xu","doi":"10.33696/neurol.5.101","DOIUrl":"10.33696/neurol.5.101","url":null,"abstract":"<p><p>Protein citrullination (PC) is a posttranslational modification (PTM) that converts a peptidyl arginine into a peptidyl citrulline. Aberrant PC is a hallmark of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, prion disease, and multiple sclerosis. Common among these diseases is a dramatic increase of PC in reactive astrocytes. Some citrullinated proteins have been identified. The most prominent are astrocytic cytoskeletal proteins such as GFAP and vimentin, and myelin protein MBP. Recent investigation in ALS has revealed new changes, including a decreased PC in neurons and an association of PC with myelin protein aggregates. These findings suggest that PC contributes to protein aggregation, neuronal dysfunction, neuroinflammation, and axonal degeneration. However, how PC impact neurodegeneration remains to be understood. Further studies are needed to understand a range of questions, from how PC modulates individual protein functions to its impact on diseases. Because of the PC's robust changes in neurodegenerative diseases, there are also prospects that this PTM may be harnessed as biomarkers, and modulation of this PTM may be an avenue for therapy. In this review, we summarize the current understanding of PC in ALS and other neurodegenerative diseases, the investigative methods for PC, and PC's potential as a biomarker and a therapeutic target.</p>","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"5 4","pages":"183-191"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Perla H. Horta-López, Jan Rícny, B. Florán-Garduño, F. García-Sierra
Conformational changes of Tau have been described to occur during its fibrillary and non-fibrillary aggregation inside neurons affected in the brain of Alzheimer’s disease (AD) patients. Two consecutive conformations have been described during the progression of the disease: an early conformation detected with the Alz-50 antibody, recognizing Tau molecules folding its amino terminus over its third repeated domain, and a later conformation involving the bending of the proline-rich region over the third repeated domain. α-1-antichymotrypsin (ACT) is an acute phase serum glycoprotein that is overexpressed in the brain of AD cases and associated with extracellular amyloid-ß aggregates. We have recently reported that in a large population of neurons affected in AD brains, Tau protein undergoing the conformational change detected by Tau-66 antibody accumulates as non-fibrillary aggregates and colocalizes with extensive accumulations of granular diffuse intracellular deposits of ACT. In this report, we further analyzed Tau-ACT interactions in the neurons from the hippocampus of AD brains. By using superresolution confocal microscopy and quantitative colocalization analysis, we corroborated the mutual association and mislocalization of conformationally altered Tau protein and ACT to the nuclear compartment. These results suggest that ACT can play an abnormal pathological role in AD by contributing to the abnormal transport of truncated and conformationally altered Tau protein to the nucleus.
据描述，在阿尔茨海默病（AD）患者大脑中受影响的神经元内，Tau的纤维状和非纤维状聚集过程中会发生构象变化。在疾病进展过程中出现了两种连续的构象：一种是用 Alz-50 抗体检测到的早期构象，即 Tau 分子将其氨基末端折叠到第三重复结构域上；另一种是涉及富脯氨酸区弯曲到第三重复结构域上的后期构象。α-1-antichymotrypsin（ACT）是一种急性期血清糖蛋白，在 AD 病例的大脑中过度表达，并与细胞外淀粉样蛋白-ß聚集相关。我们最近报告说，在大量受影响的AD脑神经元中，Tau-66抗体检测到的构象变化的Tau蛋白以非纤维状聚集体形式聚集，并与ACT的颗粒状弥漫性细胞内沉积物广泛聚集在一起。在本报告中，我们进一步分析了 AD 大脑海马区神经元中 Tau-ACT 的相互作用。通过使用超分辨率共聚焦显微镜和定量共聚焦分析，我们证实了构象改变的Tau蛋白和ACT相互关联并错位到核区。这些结果表明，ACT可通过促进截短的构象改变Tau蛋白向细胞核的异常转运，在AD中发挥异常病理作用。
{"title":"Association of Conformationally Altered Tau with α-1-antichymotrypsin in the Nuclei of Neurons in the Alzheimer's Disease Brain","authors":"Perla H. Horta-López, Jan Rícny, B. Florán-Garduño, F. García-Sierra","doi":"10.33696/neurol.4.080","DOIUrl":"https://doi.org/10.33696/neurol.4.080","url":null,"abstract":"Conformational changes of Tau have been described to occur during its fibrillary and non-fibrillary aggregation inside neurons affected in the brain of Alzheimer’s disease (AD) patients. Two consecutive conformations have been described during the progression of the disease: an early conformation detected with the Alz-50 antibody, recognizing Tau molecules folding its amino terminus over its third repeated domain, and a later conformation involving the bending of the proline-rich region over the third repeated domain. α-1-antichymotrypsin (ACT) is an acute phase serum glycoprotein that is overexpressed in the brain of AD cases and associated with extracellular amyloid-ß aggregates. We have recently reported that in a large population of neurons affected in AD brains, Tau protein undergoing the conformational change detected by Tau-66 antibody accumulates as non-fibrillary aggregates and colocalizes with extensive accumulations of granular diffuse intracellular deposits of ACT. In this report, we further analyzed Tau-ACT interactions in the neurons from the hippocampus of AD brains. By using superresolution confocal microscopy and quantitative colocalization analysis, we corroborated the mutual association and mislocalization of conformationally altered Tau protein and ACT to the nuclear compartment. These results suggest that ACT can play an abnormal pathological role in AD by contributing to the abnormal transport of truncated and conformationally altered Tau protein to the nucleus.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"104 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139239491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shadi Shiva, Shokoufeh Khanzadeh, Vahid Shohanizad, Arshin Ghaedi, Brandon Lucke-Wold
Introduction: One of the most significant current discussions in pediatrics is whether lumbar puncture (LP) should be performed in children with febrile seizure (FS) as in the past. Objectives: We compared the prevalence of meningitis among FS children before and after the pentavalent vaccine to determine the importance of the LP in these children. Methods: We performed a retrospective cross-sectional study on the prevalence and etiology of bacterial meningitis (BM) in 1314 children with FS before and after pentavalent vaccination. Results: We found that complex FS was more prevalent in patients aged under 12 months compared to other patients. The peak incidence of aseptic meningitis and BM was in the age group of 12- to18- and 18- to 36-month-old, respectively (P value <0.001 and <0.05, respectively). Children with complex FS had a significantly higher rate of BM and a lower rate of seizure recurrence than those with simple FS (P value <0.05). There was a significant relationship between getting the pentavalent vaccine and reducing the prevalence of BM and Hib-induced BM, but no SP-induced BM (P value <0.05 and 0.05 and 0.104, respectively). Conclusion: This study offers some insights into the effectiveness of the pentavalent vaccine. In addition, the low prevalence of BM in vaccinated FS cases does not support strong recommendations for LP in FS children.
{"title":"Change in Prevalence of Meningitis among Children with Febrile Seizure after the Pentavalent Vaccination","authors":"Shadi Shiva, Shokoufeh Khanzadeh, Vahid Shohanizad, Arshin Ghaedi, Brandon Lucke-Wold","doi":"10.33696/neurol.4.079","DOIUrl":"https://doi.org/10.33696/neurol.4.079","url":null,"abstract":"Introduction: One of the most significant current discussions in pediatrics is whether lumbar puncture (LP) should be performed in children with febrile seizure (FS) as in the past. Objectives: We compared the prevalence of meningitis among FS children before and after the pentavalent vaccine to determine the importance of the LP in these children. Methods: We performed a retrospective cross-sectional study on the prevalence and etiology of bacterial meningitis (BM) in 1314 children with FS before and after pentavalent vaccination. Results: We found that complex FS was more prevalent in patients aged under 12 months compared to other patients. The peak incidence of aseptic meningitis and BM was in the age group of 12- to18- and 18- to 36-month-old, respectively (P value <0.001 and <0.05, respectively). Children with complex FS had a significantly higher rate of BM and a lower rate of seizure recurrence than those with simple FS (P value <0.05). There was a significant relationship between getting the pentavalent vaccine and reducing the prevalence of BM and Hib-induced BM, but no SP-induced BM (P value <0.05 and 0.05 and 0.104, respectively). Conclusion: This study offers some insights into the effectiveness of the pentavalent vaccine. In addition, the low prevalence of BM in vaccinated FS cases does not support strong recommendations for LP in FS children.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"17 12","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134991530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Posterior quadrant epilepsy is relatively uncommon and refractory seizures from these regions are difficult to diagnose and manage. A 28-year-old woman presented for evaluation of her seizures. Scalp Electroencephalogram (EEG) showed seizures with independent onset over the right posterior and left anterior regions. Positron emission tomography (PET) scans revealed multiple regions of hypometabolism in the brain with maximum decrease in metabolism seen over the left and right precuneus and both occipital lobes. Magnetoencephalography (MEG) revealed epileptogenic dipoles over bilateral precuneus regions. Intracranial EEG revealed seizure onset from the left precuneus and left frontal regions with rapid generalization. She underwent Responsive Neurostimulation System (RNS) implantation targeting the left precuneus and left frontal regions for network modulation. She has had a 90 percent seizure reduction and remains on 2 medications as she continues to follow up in clinic. Posterior quadrant epilepsy remains a challenging condition to manage, and the use of neuromodulation may improve response rates and improve our understanding of these networks. Definite guidelines on location of electrode placement of RNS in such cases remain absent and improved understanding of such seizure networks is expected to improve our ability to target therapeutic nodes accurately to achieve greater seizure control.
{"title":"Responsive Neurostimulation for Management of Refractory Precuneus Onset Epilepsy: A Case Report","authors":"Arun Swaminathan","doi":"10.33696/neurol.4.078","DOIUrl":"https://doi.org/10.33696/neurol.4.078","url":null,"abstract":"Posterior quadrant epilepsy is relatively uncommon and refractory seizures from these regions are difficult to diagnose and manage. A 28-year-old woman presented for evaluation of her seizures. Scalp Electroencephalogram (EEG) showed seizures with independent onset over the right posterior and left anterior regions. Positron emission tomography (PET) scans revealed multiple regions of hypometabolism in the brain with maximum decrease in metabolism seen over the left and right precuneus and both occipital lobes. Magnetoencephalography (MEG) revealed epileptogenic dipoles over bilateral precuneus regions. Intracranial EEG revealed seizure onset from the left precuneus and left frontal regions with rapid generalization. She underwent Responsive Neurostimulation System (RNS) implantation targeting the left precuneus and left frontal regions for network modulation. She has had a 90 percent seizure reduction and remains on 2 medications as she continues to follow up in clinic. Posterior quadrant epilepsy remains a challenging condition to manage, and the use of neuromodulation may improve response rates and improve our understanding of these networks. Definite guidelines on location of electrode placement of RNS in such cases remain absent and improved understanding of such seizure networks is expected to improve our ability to target therapeutic nodes accurately to achieve greater seizure control.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49582862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glypican-2 as the Regeneration-Associated Gene (RAG)","authors":"K. Sakamoto, Yuji Suzuki, K. Kadomatsu","doi":"10.33696/neurol.4.076","DOIUrl":"https://doi.org/10.33696/neurol.4.076","url":null,"abstract":"","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49277190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: There is limited evidence on the relationship between anxiety and cognition in stroke patients, and no precise relationship between the two has been indicated. Objective: We aimed to explore the precise relationship between anxiety and cognition in Chinese stroke patients. Methods: This study was a cross-sectional study, 384 hospitalized stroke patients were assessed with questionnaires and scales, including the Demographic Characteristics Questionnaire, the Hamilton Anxiety Inventory (HAMA), and the Montreal Cognitive Assessment (MoCA). Results: Anxiety was present in 55.47% of the 384 patients. Univariate analysis showed that age, gender, marital status, smoking, and alcohol consumption were associated with cognition, and multiple linear regression results showed that HAMA was not independently associated with MoCA after adjusting for potential confounders (β=-0.16, 95% CI: -0.29 to- 0.03), which would be inconsistent with HAMA (subgroup) as a categorical variable (P trend of 0.004) A non-linear relationship was detected between HAMA and MoCA with an inflection point of 9. The effect sizes and confidence intervals to the left and right of the inflection point were -0.54 (-0.78 to -0.30) and 0.02 (-0.14 to -0.17), respectively. Conclusion: The relationship between anxiety and cognition is nonlinear. When the HAMA score is less than 9, anxiety and cognition are negatively correlated, and when it is greater than or equal to 9, the cognitive score will no longer decrease and is saturated.
{"title":"The Relationship between Anxiety and Cognition in Stroke Patients: A Cross-Sectional Study","authors":"Zixiu Zheng, Runluo Song, Yang-yan Song, Yanqing Wang, Yanjun Zhuang, Cong Yu, Jun Xue","doi":"10.33696/neurol.4.075","DOIUrl":"https://doi.org/10.33696/neurol.4.075","url":null,"abstract":"Background: There is limited evidence on the relationship between anxiety and cognition in stroke patients, and no precise relationship between the two has been indicated.\u0000\u0000Objective: We aimed to explore the precise relationship between anxiety and cognition in Chinese stroke patients.\u0000\u0000Methods: This study was a cross-sectional study, 384 hospitalized stroke patients were assessed with questionnaires and scales, including the Demographic Characteristics Questionnaire, the Hamilton Anxiety Inventory (HAMA), and the Montreal Cognitive Assessment (MoCA).\u0000\u0000Results: Anxiety was present in 55.47% of the 384 patients. Univariate analysis showed that age, gender, marital status, smoking, and alcohol consumption were associated with cognition, and multiple linear regression results showed that HAMA was not independently associated with MoCA after adjusting for potential confounders (β=-0.16, 95% CI: -0.29 to- 0.03), which would be inconsistent with HAMA (subgroup) as a categorical variable (P trend of 0.004) A non-linear relationship was detected between HAMA and MoCA with an inflection point of 9. The effect sizes and confidence intervals to the left and right of the inflection point were -0.54 (-0.78 to -0.30) and 0.02 (-0.14 to -0.17), respectively.\u0000\u0000Conclusion: The relationship between anxiety and cognition is nonlinear. When the HAMA score is less than 9, anxiety and cognition are negatively correlated, and when it is greater than or equal to 9, the cognitive score will no longer decrease and is saturated.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42285663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daily activity restriction is an expected physical behavior aiming to prevent falls in the older population. However, it plays dual roles in preventing falls, both positive and harmful. Therefore, the degree of daily activity restriction is proposed as a critical factor influencing the weight ratio of the positive and negative roles and finally determining the efficacy of fall prevention. Thus, quantification of daily activity restriction is essential to learn its efficacy. We proposed using activity frequency to quantify activity restriction and have testified its good sensitivity to discriminate the degree of activity restriction in older populations. We further attempted to link the degree of activity restriction with the degree of fear of falling to estimate the dual roles of activity restriction in preventing falls. Based on it, a new Composite Activity-specific Risk of Falls Scale tool has been developed. It is promising to use for guiding the modification of physical behavior to prevent falls in older populations. However, further studies are required to establish the evidence for its application.
{"title":"Daily Activity Restriction Quantification in Older Population via Using Activity Frequency: Dual Roles in Preventing Falls","authors":"Xia Shen, Lin Y. Chen, Jing X. Wang, Yan N. Jiang","doi":"10.33696/neurol.4.073","DOIUrl":"https://doi.org/10.33696/neurol.4.073","url":null,"abstract":"Daily activity restriction is an expected physical behavior aiming to prevent falls in the older population. However, it plays dual roles in preventing falls, both positive and harmful. Therefore, the degree of daily activity restriction is proposed as a critical factor influencing the weight ratio of the positive and negative roles and finally determining the efficacy of fall prevention. Thus, quantification of daily activity restriction is essential to learn its efficacy.\u0000\u0000We proposed using activity frequency to quantify activity restriction and have testified its good sensitivity to discriminate the degree of activity restriction in older populations. We further attempted to link the degree of activity restriction with the degree of fear of falling to estimate the dual roles of activity restriction in preventing falls. Based on it, a new Composite Activity-specific Risk of Falls Scale tool has been developed. It is promising to use for guiding the modification of physical behavior to prevent falls in older populations. However, further studies are required to establish the evidence for its application.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41990548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acute bacterial meningitis is a disease with an overwhelmingly high mortality rate and high incidence of adverse neurological sequelae and poor neurological recovery amongst survivors. Amongst the numerous complications of bacterial meningitis, the presence of cerebrovascular disease represents a severe disease form. Vascular involvement during bacterial meningitis has long been established by numerous pathological and angiographic studies. Cerebrovascular changes known to occur in bacterial meningitis ranging from narrowing of large arteries by vasospasm to critical stenosis/obliteration of small to medium sized arteries/arterioles by vasculitis. Not surprisingly, alterations in CBF velocities have commonly been described during the inflammatory process and may represent an important component of brain injury during meningitis. In accordance with previous studies observing a biphasic cerebral flow pattern characterized by an early but transient increase in flow velocity, mostly due to reflexive vasospasm, and later by a sustained decrease in flow velocity, likely attributable to stenotic vasculitis, cerebral ischemia is a notable complication of bacterial meningitis during the advanced disease phase. Impaired cerebral perfusion during the late stages of disease may result from a variety of factors that contribute to a vital component of cerebral injury in bacterial meningitis. The pathogenesis of cerebral ischemia with progression of disease course is less clearly understood but may involve a complex interaction between inflammatory processes, systemic dysfunction, energy impairment, neuronal damage and intracranial pressure, factors of which we aim to more precisely understand and assign a more definite contributory role in the development of cerebrovascular ischemic consequences with advanced stages of bacterial meningitis.
{"title":"Late Decrease in Cerebral Blood Flow in Bacterial Meningitis: More than a Simple Normalization of Acute Inflammatory Vessel Wall Architecture?","authors":"V. Kumar, Vignarth Shantha Kumar","doi":"10.33696/neurol.4.074","DOIUrl":"https://doi.org/10.33696/neurol.4.074","url":null,"abstract":"Acute bacterial meningitis is a disease with an overwhelmingly high mortality rate and high incidence of adverse neurological sequelae and poor neurological recovery amongst survivors. Amongst the numerous complications of bacterial meningitis, the presence of cerebrovascular disease represents a severe disease form. Vascular involvement during bacterial meningitis has long been established by numerous pathological and angiographic studies. Cerebrovascular changes known to occur in bacterial meningitis ranging from narrowing of large arteries by vasospasm to critical stenosis/obliteration of small to medium sized arteries/arterioles by vasculitis. Not surprisingly, alterations in CBF velocities have commonly been described during the inflammatory process and may represent an important component of brain injury during meningitis. In accordance with previous studies observing a biphasic cerebral flow pattern characterized by an early but transient increase in flow velocity, mostly due to reflexive vasospasm, and later by a sustained decrease in flow velocity, likely attributable to stenotic vasculitis, cerebral ischemia is a notable complication of bacterial meningitis during the advanced disease phase. Impaired cerebral perfusion during the late stages of disease may result from a variety of factors that contribute to a vital component of cerebral injury in bacterial meningitis. The pathogenesis of cerebral ischemia with progression of disease course is less clearly understood but may involve a complex interaction between inflammatory processes, systemic dysfunction, energy impairment, neuronal damage and intracranial pressure, factors of which we aim to more precisely understand and assign a more definite contributory role in the development of cerebrovascular ischemic consequences with advanced stages of bacterial meningitis.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45414280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Hazel, Mike Hefferan, Kateryna Schwartz, N. Yu, K. Johe, Michael Levy
Glial cells play a critical role in the development and function of the mammalian central nervous system (CNS). Among other roles, these cells provide the myelin sheath needed for the efficient propagation of impulses along nerve fibers, provide trophic support for neuronal cells, and remove toxins and excess neurotransmitters from the interstitial space. Transplantation of glial cells or glial progenitors into the diseased or injured CNS can provide therapeutic benefits. However, generation of therapeutically useful quantities of glia, in particular oligodendrocytes, is technically challenging. Furthermore, generation of glial precursors from sources such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells poses potential safety risks due to the tumorigenic potential of undifferentiated cells. Here we report a method that enables the efficient generation and expansion of glial precursors from tissue-restricted neural stem cells (NSC). NSC-derived glial precursors can be expanded extensively in culture and retain the capacity to differentiate into oligodendrocytes and astrocytes in vitro and in vivo. Upon transplantation into different animal models of demyelination a substantial proportion of these cells become oligodendrocytes with the capacity to myelinate host axons. These results demonstrate that tissue-restricted human neural stem cells can serve as an efficient source for myelinating oligodendrocytes with therapeutic potential.
{"title":"Generation of Human Oligodendrocyte Progenitors for Treatment of Demyelinating Diseases and Spinal Cord Injury","authors":"T. Hazel, Mike Hefferan, Kateryna Schwartz, N. Yu, K. Johe, Michael Levy","doi":"10.33696/neurol.4.072","DOIUrl":"https://doi.org/10.33696/neurol.4.072","url":null,"abstract":"Glial cells play a critical role in the development and function of the mammalian central nervous system (CNS). Among other roles, these cells provide the myelin sheath needed for the efficient propagation of impulses along nerve fibers, provide trophic support for neuronal cells, and remove toxins and excess neurotransmitters from the interstitial space. Transplantation of glial cells or glial progenitors into the diseased or injured CNS can provide therapeutic benefits. However, generation of therapeutically useful quantities of glia, in particular oligodendrocytes, is technically challenging. Furthermore, generation of glial precursors from sources such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells poses potential safety risks due to the tumorigenic potential of undifferentiated cells. Here we report a method that enables the efficient generation and expansion of glial precursors from tissue-restricted neural stem cells (NSC). NSC-derived glial precursors can be expanded extensively in culture and retain the capacity to differentiate into oligodendrocytes and astrocytes in vitro and in vivo. Upon transplantation into different animal models of demyelination a substantial proportion of these cells become oligodendrocytes with the capacity to myelinate host axons. These results demonstrate that tissue-restricted human neural stem cells can serve as an efficient source for myelinating oligodendrocytes with therapeutic potential.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41359698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isha Snehal, Kanchan Kumari, M. Schissel, Arun Swaminathan
Purpose: Routine inpatient EEGs have been part of epilepsy practices for years. We aim to improve current routine EEG practices by studying their role at a large university hospital. Methods: Inpatient routine EEGs from January-July 2021 were included and patients <5 yrs., EEGs repeated on the same patient were excluded. Indications, floor status, abnormality, day of study, neurology consultation, results, treatment changes, discharge status, and prior AED use were analyzed using SAS 9.4. Results: The mean age for 250 patients was 57.27 yrs., where 54.22% were males and 45.78% were females. Indications listed were 26.5% altered mental status, 59.83% seizures, and 13.65% others. 87.36% of ICU patients had abnormal EEG vs 73.75% of floor patients. A significant association (p=0.0147) was found between floor status and EEG results. Abnormalities were 44% generalized slowing, 23.6% focal slowing, 9.2% epileptiform activity, and 23.2% others. Treatment was changed in 21.03% with abnormal vs 5.56% with normal EEG. AEDs were added in 18.46% with abnormal vs 3.7% with normal EEG. A significant association (p=0.014) was found between Neurology consultation and treatment change and with AED addition respectively. EEG result was associated with treatment change and AED addition. “Abnormal EEG” was significantly associated with further study. A significant association (p=0.0351) was found between EEG results and discharge status. 53.82% of patients were not on AED before EEG vs 46.18%. Prior AED had no association with EEG results. Conclusions: It is helpful to consult Neurology. Longer duration of routine EEGs may not show abnormalities. Routine EEG facilitates discharges and guides further workup.
{"title":"Benefits of Routine Inpatient EEG in Practice: Experience from a Level 4 University Hospital","authors":"Isha Snehal, Kanchan Kumari, M. Schissel, Arun Swaminathan","doi":"10.33696/neurol.4.071","DOIUrl":"https://doi.org/10.33696/neurol.4.071","url":null,"abstract":"Purpose: Routine inpatient EEGs have been part of epilepsy practices for years. We aim to improve current routine EEG practices by studying their role at a large university hospital. Methods: Inpatient routine EEGs from January-July 2021 were included and patients <5 yrs., EEGs repeated on the same patient were excluded. Indications, floor status, abnormality, day of study, neurology consultation, results, treatment changes, discharge status, and prior AED use were analyzed using SAS 9.4. Results: The mean age for 250 patients was 57.27 yrs., where 54.22% were males and 45.78% were females. Indications listed were 26.5% altered mental status, 59.83% seizures, and 13.65% others. 87.36% of ICU patients had abnormal EEG vs 73.75% of floor patients. A significant association (p=0.0147) was found between floor status and EEG results. Abnormalities were 44% generalized slowing, 23.6% focal slowing, 9.2% epileptiform activity, and 23.2% others. Treatment was changed in 21.03% with abnormal vs 5.56% with normal EEG. AEDs were added in 18.46% with abnormal vs 3.7% with normal EEG. A significant association (p=0.014) was found between Neurology consultation and treatment change and with AED addition respectively. EEG result was associated with treatment change and AED addition. “Abnormal EEG” was significantly associated with further study. A significant association (p=0.0351) was found between EEG results and discharge status. 53.82% of patients were not on AED before EEG vs 46.18%. Prior AED had no association with EEG results. Conclusions: It is helpful to consult Neurology. Longer duration of routine EEGs may not show abnormalities. Routine EEG facilitates discharges and guides further workup.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44501060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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