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Arc/Arg3.1 expression in the brain tissues during the learning process in Alzheimer's disease animal models 阿尔茨海默病动物模型学习过程中脑组织中Arc/Arg3.1的表达
Q3 Multidisciplinary Pub Date : 2023-09-29 DOI: 10.54101/acen.2023.3.6
Maria V. Ryazanova, Anton S. Averchuk, Alla V. Stavrovskaya, Natalia A. Rozanova, Svetlana V. Novikova, Alla B. Salmina
Introduction. Arc/Arg3.1 is a common marker of neuronal activation for learning and memorizing. Some experimental data show the Arc/Arg3.1 expression in the post-mitotic neurons of the neurogenic niches. At the same time, we still have to understand the importance of such an expression for neurogenesis induced by the learning or memorizing processes, in health and in disease. Objective: to evaluate the changes in Arc/Arg3.1 expression in the post-mitotic neurons and to assess the proliferative activity of the neurogenic niche cells in Alzheimer's disease animal models. Materials and methods. We divided the C57Bl/6В mice into 2 groups: experimental (n = 15) and control (n = 15). The experimental group were injected with the amyloid- oligomers 2535 in their CA1 hippocampal region while the control mice received normal saline injections in the same region. Passive Avoidance Test (PAT) was used to assess the cognitive functions from the day 9 after the intervention. One hour after each test session we collected the samples of brain tissues to immunohistochemically assess them for the Arc/Arg3.1 expression and PCNA cell proliferation marker. Results. At day 11 the count of Arc/Arg3.1+NeuN+ cells in the subgranular zone had significantly increased. In animal neurodegeneration models the 1st and 2nd PAT sessions were associated with a significant increase in Arc/Arg3.1+NeuN+ cells, although by the day 11 their count significantly decreased. The count of Arc/Arg3.1+ cells in the subventricular and subgranular zones had increased after the 3rd PAT session in the control group while in Alzheimer's disease animal models this was observed only after the 2nd PAT session. Preserved Arc/Arg3.1 expression in the subventricular zone is associated with the increased PCNA cell prolifera- tion marker expression. At the same time, the toxic effect of the amyloid- oligomers suppressed the cells' proliferative activity in the subgranular zone at day 9. Conclusions. Despite the toxic effect of the amyloid- oligomers 2535, the post-mitotic neurons of the neurogenic niches retained the ability to express Arc/Arg3.1 in vivo. The obtained results show a transient increase in sensitivity of the post-mitotic neurons of the neurogenic niches for the learning stimuli in the early stages of the Alzheimer-type neurodegeneration.
介绍。Arc/Arg3.1是学习和记忆神经元激活的常见标记物。一些实验数据表明,Arc/Arg3.1在神经源性神经龛的有丝分裂后神经元中表达。同时,我们还必须了解这种表达对于由学习或记忆过程诱导的神经发生,在健康和疾病中的重要性。目的:探讨阿尔茨海默病动物模型中有丝分裂后神经元中Arc/Arg3.1表达的变化及神经源性生态位细胞的增殖活性。 材料和方法。我们将C57Bl/6В小鼠分为实验组(n = 15)和对照组(n = 15)。实验组小鼠在CA1海马区注射淀粉样蛋白低聚物2535,对照组小鼠在CA1海马区注射生理盐水。从干预后第9天开始,采用被动回避测验(PAT)评估认知功能。每次测试1小时后,我们收集脑组织样本,用免疫组织化学方法评估它们的Arc/Arg3.1表达和PCNA细胞增殖标志物。 结果。第11天,亚颗粒区Arc/Arg3.1+NeuN+细胞数量显著增加。在动物神经变性模型中,第1次和第2次PAT与Arc/Arg3.1+NeuN+细胞的显著增加有关,尽管到第11天它们的计数显著减少。在对照组中,第三次PAT后脑室下和颗粒下区Arc/Arg3.1+细胞计数增加,而在阿尔茨海默病动物模型中,这种情况仅在第二次PAT后观察到。在脑室下区保存的Arc/Arg3.1表达与PCNA细胞增殖标志物表达的增加有关。同时,淀粉样蛋白低聚物的毒性作用在第9天抑制了细胞在亚颗粒区的增殖活性。 结论。尽管淀粉样蛋白低聚物2535具有毒性作用,但神经源性神经龛的有丝分裂后神经元在体内保留了表达Arc/Arg3.1的能力。所获得的结果表明,在阿尔茨海默型神经变性的早期阶段,神经源性小生境的有丝分裂后神经元对学习刺激的敏感性有短暂的增加。
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 Objective: to evaluate the changes in Arc/Arg3.1 expression in the post-mitotic neurons and to assess the proliferative activity of the neurogenic niche cells in Alzheimer's disease animal models.
 Materials and methods. We divided the C57Bl/6В mice into 2 groups: experimental (n = 15) and control (n = 15). The experimental group were injected with the amyloid- oligomers 2535 in their CA1 hippocampal region while the control mice received normal saline injections in the same region. Passive Avoidance Test (PAT) was used to assess the cognitive functions from the day 9 after the intervention. One hour after each test session we collected the samples of brain tissues to immunohistochemically assess them for the Arc/Arg3.1 expression and PCNA cell proliferation marker.
 Results. At day 11 the count of Arc/Arg3.1+NeuN+ cells in the subgranular zone had significantly increased. In animal neurodegeneration models the 1st and 2nd PAT sessions were associated with a significant increase in Arc/Arg3.1+NeuN+ cells, although by the day 11 their count significantly decreased. The count of Arc/Arg3.1+ cells in the subventricular and subgranular zones had increased after the 3rd PAT session in the control group while in Alzheimer's disease animal models this was observed only after the 2nd PAT session. Preserved Arc/Arg3.1 expression in the subventricular zone is associated with the increased PCNA cell prolifera- tion marker expression. At the same time, the toxic effect of the amyloid- oligomers suppressed the cells' proliferative activity in the subgranular zone at day 9.
 Conclusions. Despite the toxic effect of the amyloid- oligomers 2535, the post-mitotic neurons of the neurogenic niches retained the ability to express Arc/Arg3.1 in vivo. The obtained results show a transient increase in sensitivity of the post-mitotic neurons of the neurogenic niches for the learning stimuli in the early stages of the Alzheimer-type neurodegeneration.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135193689","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}
引用次数: 0
Pathophysiology and biomechanics of stretch-induced peripheral nerve injuries 拉伸性周围神经损伤的病理生理学和生物力学
Q3 Multidisciplinary Pub Date : 2023-09-29 DOI: 10.54101/acen.2023.3.7
Yulia V. Karakulova, Gayane Z. Kloyan, Sergey V. Muravev, Ivan D. Shitoev, Vladislav N. Nikitin, Maria D. Ivanova
Objective: to investigate pathophysiology and biomechanics of the nerve stretching and to form a biomechanical model of a nerve stretch injury. Materials and methods. We analyzed and summarized the data from open access sources (eLibrary, Scopus, Web of Science, PubMed) with unlimited search depth. A search was performed using the following keywords: растяжение нерва (English: nerve stretching), stretching nerve, biomechanical nerve stretching, nerve stretching injury. Results. Here are presented key historical information and biochemical, neurophysiological, and biomechanical events related to a nerve stretch injury. Objective experimental data on the nerve stretching process are summarized. Conclusions. A nerve is a heterogeneous elastic cord, which can be slightly stretched under physiological conditions due to the involvement of its sheath structures. In a stretched nerve, ischemic lesions have an early onset and further become irreversible. Nerve conduction disorders occur, resulting in a severe neurological deficit. When the nerve is stretched by more than a third, it ruptures and the sequence in which fragmented neural structures occur during nerve tension remains unclear.
目的:探讨神经拉伸的病理生理学和生物力学,建立神经拉伸损伤的生物力学模型。材料和方法。我们以无限的搜索深度分析和总结了来自开放获取资源(eLibrary, Scopus, Web of Science, PubMed)的数据。使用以下关键词进行检索:растяжение нерва(英文:nerve stretching),神经拉伸,生物力学神经拉伸,神经拉伸损伤。 结果。这里介绍了与神经拉伸损伤相关的关键历史信息和生化、神经生理学和生物力学事件。客观总结了神经伸展过程的实验数据。 结论。神经是一种不均匀的弹性索,由于其鞘结构的参与,在生理条件下可以轻微拉伸。在拉伸的神经中,缺血性病变早发,并进一步变得不可逆转。神经传导紊乱,导致严重的神经功能缺损。当神经被拉伸超过三分之一时,它就会断裂,神经紧张时神经结构碎片的顺序尚不清楚。
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 Materials and methods. We analyzed and summarized the data from open access sources (eLibrary, Scopus, Web of Science, PubMed) with unlimited search depth. A search was performed using the following keywords: растяжение нерва (English: nerve stretching), stretching nerve, biomechanical nerve stretching, nerve stretching injury.
 Results. Here are presented key historical information and biochemical, neurophysiological, and biomechanical events related to a nerve stretch injury. Objective experimental data on the nerve stretching process are summarized.
 Conclusions. A nerve is a heterogeneous elastic cord, which can be slightly stretched under physiological conditions due to the involvement of its sheath structures. In a stretched nerve, ischemic lesions have an early onset and further become irreversible. Nerve conduction disorders occur, resulting in a severe neurological deficit. When the nerve is stretched by more than a third, it ruptures and the sequence in which fragmented neural structures occur during nerve tension remains unclear.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135246636","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}
引用次数: 0
Three-year survival rate and changes in the level of consciousness in outpatients after severe brain injuries 重型颅脑损伤后门诊患者三年生存率及意识水平变化
Q3 Multidisciplinary Pub Date : 2023-09-29 DOI: 10.54101/acen.2023.3.4
Iuliia Y. Nekrasova, Andrey V. Grechko, Mikhail Kanarskii, Ilya V. Borisov, Pranil Pradhan, Aleksey V Mukhin, Dmitry S. Yankevich, Marina V. Petrova
Introduction. There is a worldwide lack of statistical data about the patients with chronic disorders of consciousness (DOC). In Russia, there are no such data at all. Objective: to perform the first study in Russia to assess the survival rate and changes in the level of consciousness in outpatients with the chronic DOC after their hospital discharge as well as to identify the predictors of survival and improvement in the level of consciousness. Materials and methods. All the participants (n = 142) underwent their treatment and rehabilitation in Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology from January 2016 to January 2020. We recorded the changes in patient's vital status and their level of consciousness at the endpoints of 3, 6, 12, 24, and 36 months from the brain injury (both for hospital and outpatient stages). We used the KaplanMeier method to assess the survival rate. We also used the logistic regression model to determine the correlation between the predictors of the survival and the improvement in the level of consciousness at baseline and 36 months after the injury. Results. The mortality rate in the study group 3 years after the brain injury was 86.6%. Regardless of the survival rate, the level of consciousness had significantly improved (i.e., they regained communication) in 22.5% of patients within 3 years after the index event. The statistically significant final model of the regression analysis (for 142 patients) showed that younger age and higher overall CRS-R score improved the survival rate. The logistic regression model used to determine the predictors of the improvement in the level of consciousness among the survivors gave no significant results. Conclusions. High mortality rate among the outpatients, whose level of consciousness had improved at discharge, proves the ineffectiveness of the outpatient rehabilitation. Thus, we need to find a way to improve it. The authors hope that the data obtained in this study will form the basis of their research.
介绍。关于慢性意识障碍(DOC)患者的统计资料在世界范围内缺乏。在俄罗斯,根本没有这样的数据。目的:在俄罗斯开展首个慢性DOC门诊患者出院后生存率及意识水平变化的研究,并探讨其生存及意识水平改善的预测因素。 材料和方法。所有参与者(n = 142)于2016年1月至2020年1月在联邦重症医学与康复研究与临床中心接受治疗和康复。我们记录了患者在脑损伤后3、6、12、24和36个月的生命状态和意识水平的变化(包括住院和门诊阶段)。我们采用KaplanMeier法评估生存率。我们还使用logistic回归模型来确定生存预测因素与基线和损伤后36个月的意识水平改善之间的相关性。 结果。研究组脑损伤后3年死亡率为86.6%。无论生存率如何,在指数事件发生后的3年内,22.5%的患者的意识水平显著提高(即他们恢复了沟通)。回归分析的最终模型(142例患者)显示,年龄越小,总CRS-R评分越高,生存率越高。用于确定幸存者意识水平改善预测因素的逻辑回归模型没有给出显著结果。 结论。门诊病人死亡率高,出院时意识水平有所提高,证明门诊康复效果不佳。因此,我们需要找到一种方法来改进它。作者希望在这项研究中获得的数据将成为他们研究的基础。
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 Objective: to perform the first study in Russia to assess the survival rate and changes in the level of consciousness in outpatients with the chronic DOC after their hospital discharge as well as to identify the predictors of survival and improvement in the level of consciousness.
 Materials and methods. All the participants (n = 142) underwent their treatment and rehabilitation in Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology from January 2016 to January 2020. We recorded the changes in patient's vital status and their level of consciousness at the endpoints of 3, 6, 12, 24, and 36 months from the brain injury (both for hospital and outpatient stages). We used the KaplanMeier method to assess the survival rate. We also used the logistic regression model to determine the correlation between the predictors of the survival and the improvement in the level of consciousness at baseline and 36 months after the injury.
 Results. The mortality rate in the study group 3 years after the brain injury was 86.6%. Regardless of the survival rate, the level of consciousness had significantly improved (i.e., they regained communication) in 22.5% of patients within 3 years after the index event. The statistically significant final model of the regression analysis (for 142 patients) showed that younger age and higher overall CRS-R score improved the survival rate. The logistic regression model used to determine the predictors of the improvement in the level of consciousness among the survivors gave no significant results.
 Conclusions. High mortality rate among the outpatients, whose level of consciousness had improved at discharge, proves the ineffectiveness of the outpatient rehabilitation. Thus, we need to find a way to improve it. The authors hope that the data obtained in this study will form the basis of their research.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135193679","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}
引用次数: 0
Clinical markers for unfavorable course of multiple sclerosis 多发性硬化不良病程的临床标志
Q3 Multidisciplinary Pub Date : 2023-09-29 DOI: 10.54101/acen.2023.3.5
Mariya S. Matrosova, Galina N. Belskaya, Vasiliy V. Bryukhov, Ekaterina V. Popova, Marina V. Krotenkova
Objective. To study possible clinical markers associated with the unfavorable course of multiple sclerosis and its transition to a progressive subtype. Materials and methods. This prospective study included healthy volunteers and patients with relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS). For a comprehensive clinical evaluation, the participants completed the Timed 25-Foot Walk Test (T25-FW), Nine-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Fatigue test, and MSProDiscuss questionnaires. Then we compared the results between the groups. Results. We found significant differences between the groups in regard to most of the tests. Furthermore, we proposed a composite clinical score (CCS) based on T25-FW, SDMT, and 9-HPT results (for both hands). Discussion. Our CCS can be a useful clinical tool to determine the most likely course of multiple sclerosis at a certain timepoint.
目标。研究与多发性硬化症不良病程及其向进行性亚型转变相关的可能临床标志物。 材料和方法。这项前瞻性研究包括健康志愿者和复发-缓解型多发性硬化症(RRMS)、继发性进行性多发性硬化症(SPMS)、原发性进行性多发性硬化症(PPMS)患者。为了进行全面的临床评估,参与者完成了25英尺步行测试(T25-FW)、九孔钉测试(9-HPT)、符号数字模式测试(SDMT)、疲劳测试和MSProDiscuss问卷调查。然后比较各组结果。 结果。我们发现,在大多数测试中,两组之间存在显著差异。此外,我们提出了基于T25-FW、SDMT和9-HPT结果的综合临床评分(CCS)(双手)。 讨论。我们的CCS是一种有用的临床工具,可以在某个时间点确定多发性硬化症最可能的病程。
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 Materials and methods. This prospective study included healthy volunteers and patients with relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS). For a comprehensive clinical evaluation, the participants completed the Timed 25-Foot Walk Test (T25-FW), Nine-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Fatigue test, and MSProDiscuss questionnaires. Then we compared the results between the groups.
 Results. We found significant differences between the groups in regard to most of the tests. Furthermore, we proposed a composite clinical score (CCS) based on T25-FW, SDMT, and 9-HPT results (for both hands).
 Discussion. Our CCS can be a useful clinical tool to determine the most likely course of multiple sclerosis at a certain timepoint.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135246493","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}
引用次数: 0
Clinical Exome Sequencing in Patients with Undifferentiated General Developmental Delay and Intellectual Disabilities 未分化性一般发育迟缓和智力残疾患者的临床外显子组测序
Q3 Multidisciplinary Pub Date : 2023-06-21 DOI: 10.54101/acen.2023.2.4
D. I, Viktoriya A. Ioksha, T. Proskokova
Introduction. Each fifth neurodevelopmental disorder is diagnosed in massively parallel sequencing only. Objective: to present the experience of exome sequencing in children with undifferentiated general developmental delay and intellectual disabilities. Materials and methods. We assessed 33 patients (19 males and 14 females) at the age of 4.5 2.4 years with general developmental delay and intellectual disabilities. We studied patients' medical and family histories and their neurological statuses as well as the findings of neuropsychological testing and clinical exome sequencing. Results.The effectiveness of clinical exome sequencing in the sample was 39.4% (MECP2, WDR45, SYNJ1, ADAR, PMM2, SHANK3, KMT5B, UBE3A, PTPN11, CTNNB1, and MTOR mutations). The pathogenic variants were significantly more prevalent in the patients with motor development delay, 53.8% of patients (P .05). Most incident conditions included insomnias (46.2%), autism spectrum disorders (38.5%), developmental regression (38.5%), and epilepsy (38.5%). Genetic disorders were more common in the female patients . Conclusion. With the study results, we can suppose that ca. 40% of patients with undifferentiated general developmental delay and intellectual disabilities had genetic disorders and, therefore, needed further evaluation with molecular genetic testing.
介绍。只有五分之一的神经发育障碍是通过大规模平行测序诊断出来的。目的:介绍未分化性一般发育迟缓和智力残疾儿童外显子组测序的经验。材料和方法。我们评估了33例年龄为4.5 - 2.4岁的一般发育迟缓和智力障碍患者(男性19例,女性14例)。我们研究了患者的病史和家族史,他们的神经系统状况,以及神经心理测试和临床外显子组测序的结果。结果。样品临床外显子组测序的有效性为39.4% (MECP2、WDR45、SYNJ1、ADAR、PMM2、SHANK3、KMT5B、UBE3A、PTPN11、CTNNB1和MTOR突变)。发病变异在运动发育迟缓患者中更为普遍,占53.8% (P < 0.05)。大多数事件包括失眠(46.2%)、自闭症谱系障碍(38.5%)、发育倒退(38.5%)和癫痫(38.5%)。遗传疾病在女性患者中更为常见。结论。根据研究结果,我们可以假设约40%的未分化性一般发育迟缓和智力残疾患者患有遗传疾病,因此需要通过分子基因检测进一步评估。
{"title":"Clinical Exome Sequencing in Patients with Undifferentiated General Developmental Delay and Intellectual Disabilities","authors":"D. I, Viktoriya A. Ioksha, T. Proskokova","doi":"10.54101/acen.2023.2.4","DOIUrl":"https://doi.org/10.54101/acen.2023.2.4","url":null,"abstract":"Introduction. Each fifth neurodevelopmental disorder is diagnosed in massively parallel sequencing only. \u0000Objective: to present the experience of exome sequencing in children with undifferentiated general developmental delay and intellectual disabilities. \u0000Materials and methods. We assessed 33 patients (19 males and 14 females) at the age of 4.5 2.4 years with general developmental delay and intellectual disabilities. We studied patients' medical and family histories and their neurological statuses as well as the findings of neuropsychological testing and clinical exome sequencing. \u0000Results.The effectiveness of clinical exome sequencing in the sample was 39.4% (MECP2, WDR45, SYNJ1, ADAR, PMM2, SHANK3, KMT5B, UBE3A, PTPN11, CTNNB1, and MTOR mutations). The pathogenic variants were significantly more prevalent in the patients with motor development delay, 53.8% of patients (P .05). Most incident conditions included insomnias (46.2%), autism spectrum disorders (38.5%), developmental regression (38.5%), and epilepsy (38.5%). Genetic disorders were more common in the female patients . \u0000Conclusion. With the study results, we can suppose that ca. 40% of patients with undifferentiated general developmental delay and intellectual disabilities had genetic disorders and, therefore, needed further evaluation with molecular genetic testing.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74417358","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}
引用次数: 0
Morphological Changes in Neural Progenitors Derived from Human Induced Pluripotent Stem Cells and Transplanted into the Striatum of a Parkinson's Disease Rat Model 人诱导多能干细胞提取神经祖细胞并移植到帕金森病大鼠纹状体的形态学改变
Q3 Multidisciplinary Pub Date : 2023-06-21 DOI: 10.54101/acen.2023.2.6
D. Voronkov, A. Stavrovskaya, O. Lebedeva, Wen Li, Artem S. Olshansky, Anastasia S. Gushchina, M. R. Kapkaeva, A. Bogomazova, M. Lagarkova, S. Illarioshkin
Introduction. Development of cell therapy for Parkinson's disease (PD) requires protocols based on transplantation of neurons derived from human induced pluripotent stem cells (hiPSCs) into the damaged area of the brain. Objective: to characterize neurons transplanted into a rat brain and evaluate neural transplantation efficacy using a PD animal model. Materials and methods. Neurons derived from hiPSCs (IPSRG4S line) were transplanted into the striatum of rats after intranigral injection of 6-hydroxydopamine (6-OHDA). Immunostaining was performed to identify expression of glial and neuronal markers in the transplanted cells within 224 weeks posttransplant. Results. 4 weeks posttransplant we observed increased expression of mature neuron markers, decreased expression of neural progenitor markers, and primary pro-inflammatory response of glial cells in the graft. Differentiation and maturation of neuronal cells in the graft lasted over 3 months. At 3 and 6 months we detected 2 graft zones: one mainly contained the transplanted neurons and the other human astrocytes. We detected human neurites in the corpus callosum and surrounding striatal tissue and large human tyrosine hydroxylase-expressing neurons in the graft. Conclusion. With graft's morphological characteristics identified at different periods we can better understand pathophysiology and temporal patterns of new dopaminergic neurons integration and striatal reinnervation in a rat PD model in the long-term postoperative period.
介绍。帕金森氏病(PD)细胞治疗的发展需要基于人类诱导多能干细胞(hiPSCs)衍生的神经元移植到大脑受损区域的方案。目的:建立PD动物模型,观察神经元移植到大鼠脑内的特征,评价神经移植的效果。材料和方法。将hipsc (IPSRG4S系)衍生的神经元在黑质内注射6-羟多巴胺(6-OHDA)后移植到大鼠纹状体中。免疫染色检测移植细胞中胶质和神经元标志物的表达,时间为移植后224周。结果:移植后4周,我们观察到成熟神经元标志物的表达增加,神经祖细胞标志物的表达减少,移植物胶质细胞的原发性促炎反应。移植神经细胞的分化和成熟持续3个月以上。在3和6个月时,我们检测到2个移植物区:一个主要是移植的神经元,另一个是人类星形胶质细胞。我们在胼胝体和周围纹状体组织中检测到人类神经突,在移植物中检测到大量表达酪氨酸羟化酶的人类神经元。结论。通过确定不同时期的移植物形态学特征,我们可以更好地了解大鼠PD模型术后长期多巴胺能神经元整合和纹状体再神经支配的病理生理和时间模式。
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引用次数: 0
Role of Inflammatory Mediators, Growth Factors, and Osteodystrophy in Recurrent Lumbar Disk Herniation 炎症介质、生长因子和骨营养不良在复发性腰椎间盘突出症中的作用
Q3 Multidisciplinary Pub Date : 2023-06-21 DOI: 10.54101/acen.2023.2.5
Vladimir A. Chekhonatskiy, O. Dreval, A. Kuznetsov, A. Chekhonatskiy, N. Zakharova, E. Grishina, A. V. Gorozhanin, Vera V. Volna
Introduction. Reintervention in patients with spinal disk herniation is shown to significantly decrease likelihood of favorable outcomes in the postoperative period. Thus, it is important to individually assess risk factors for and likelihood of spinal disk herniation recurrence for each patient, and choose a suitable surgical option. Objective: to evaluate changes in the levels of immunoregulatory mediators in the blood serum and extracted spinal disc tissue of allegedly healthy individuals and patients with lumbar disk herniation relapses. Materials and methods. We examined 60 patients. The control group included 19 patients with traumatic spinal cord injuries at the lumbar level. The main group included 41 patients with spinal disk herniation. Twenty-two individuals had primary herniation while 11 patients presented with single clinical and neurological relapses at the pre-operated lumbar level and 8 patients presented with recurrent relapses. Solid-phase enzyme immunoassay detected proinflammatory cytokines (interleukin-6, tumor necrosis factor-), chemokines (interleukin-8, monocyte chemoattractant protein-1), growth factors (vascular endothelial growth factor, transforming growth factor-1), and osteodestruction markers (osteoprogesterin, matrix metalloproteinase-8) in the blood serum and the extracted spinal disc tissue. Results. We found that spinal disk destruction and chronic inflammation developed with both locally and generally elevating levels of proinflammatory cytokines/chemokines, growth factors, and matrix metalloproteinase 8. Conclusion. The results emphasize the significance of local changes in the studied parameters to choose and plan personalized surgical treatment in patients with spinal disk herniation.
介绍。椎间盘突出症患者的再干预可显著降低术后良好预后的可能性。因此,对每位患者单独评估椎间盘突出症复发的危险因素和可能性,并选择合适的手术方案是很重要的。目的:评价所谓健康个体和腰椎间盘突出症复发患者血清和提取的椎间盘组织中免疫调节介质水平的变化。材料和方法。我们检查了60个病人。对照组为19例腰段创伤性脊髓损伤患者。主要组为41例椎间盘突出症患者。22例患者为原发性疝出,11例患者在术前腰椎水平出现单一临床和神经系统复发,8例患者出现复发。固相酶免疫法检测血清及提取的椎间盘组织中促炎因子(白细胞介素-6、肿瘤坏死因子-)、趋化因子(白细胞介素-8、单核细胞趋化蛋白-1)、生长因子(血管内皮生长因子、转化生长因子-1)、骨破坏标志物(骨黄体酮、基质金属蛋白酶-8)。结果。我们发现,椎间盘破坏和慢性炎症随着局部和普遍的促炎细胞因子/趋化因子、生长因子和基质金属蛋白酶8水平的升高而发展。结论。结果强调了研究参数的局部变化对椎间盘突出症患者选择和计划个性化手术治疗的意义。
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引用次数: 0
Assessment of Biomarker Profile in Patients Post Carotid Angioplasty and Stenting 颈动脉血管成形术和支架植入术后患者生物标志物的评估
Q3 Multidisciplinary Pub Date : 2023-06-21 DOI: 10.54101/acen.2023.2.1
М.М. Tanashyan, V. Annushkin, A. Raskurazhev, O. Lagoda, Аlla А. Shabalina, R. Medvedev, V. Shchipakin
Introduction. Cardiovascular diseases are predominantly caused by atherosclerosis as a multifactorial chronic condition. Alterations in the hematological system and the blood vessel wall are considered as highly significant for onset and development of cerebrovascular disorders associated with atherosclerosis. Biomarkers as measurable indicators are to verify abnormal activity. Objective: to assess atherogenesis biomarkers in patients after carotid angioplasty and stenting (CAS) as associated with development of cerebrovascular disease. Materials and methods. We evaluated 50 individuals (50% men, 50% women; average age 65.4 6.4 years) with established cerebrovascular disease associated with brain atherosclerosis. All of them had hemodynamically significant abnormalities in the internal carotid artery (ICA) with both symptomatic (stenosis 60% and more) and asymptomatic (stenosis 70% and more) stenoses confirmed by duplex scanning of the brachiocephalic arteries. All patients underwent CAS as indicated. Before and 1 year after the intervention, we performed clinical and neurological examinations, brain magnetic resonance imaging, and laboratory tests of atherogenesis biomarkers. Results. At baseline, all the individuals demonstrated a pro-atherogenic shift in the assessed indicators, predominantly markers of extracellular matrix degradation, inflammation and atherogenesis (including osteoprotegerin and chromogranin А). Additionally, we established a direct correlation between osteoprotegerin levels and the characteristics of mostly hyperechoic atherosclerotic plaques (r = 0.29; p 0.05). A year later, no signs of restenosis were shown in follow-up ultrasound assessment of stented arteries in any patient. In 1 year post CAS, we found significant changes in the levels of osteoprotegerin (decrease to 1.765 pg/mL [1.592; 1.937]; p 0.05) and chromogranin А (elevation to 31.3 g/L [13.9; 90.7]; p 0.05). Re-assessment demonstrated association between changes in the pattern of the nitrogen oxide system, which tends to improve (NO elevation to 38.23 mol/L [32.95; 43.51]; p 0.001), and atheroprotective shift in the morphology of atherosclerotic plaques and biomarker profile. Conclusion. Prospective, 1-year long observation for patients who underwent CAS for symptomatic/asymptomatic hemodynamically significant ICA stenoses revealed favourable atheroprotective shift in both ultrasound and hematological atherogenesis biomarker ratio. This shift contributed to the absence of cerebral atherosclerosis progression during the follow-up. The process may be mediated by chromogranin А and osteoprotegerin, and their further research is needed from perspective of atherogenesis.
介绍。心血管疾病主要由动脉粥样硬化引起,是一种多因素慢性疾病。血液系统和血管壁的改变被认为是与动脉粥样硬化相关的脑血管疾病发生和发展的重要因素。生物标志物作为可测量的指标,用于验证异常活动。目的:评估颈动脉成形术和支架植入术(CAS)后患者动脉粥样硬化生物标志物与脑血管疾病发展的相关性。材料和方法。我们评估了50个人(50%的男性,50%的女性;平均年龄65.4 - 6.4岁,伴有脑血管疾病合并脑动脉粥样硬化。所有患者均有明显的颈内动脉血流动力学异常,经头臂动脉双相扫描证实有症状(狭窄60%及以上)和无症状(狭窄70%及以上)狭窄。所有患者均行CAS治疗。在干预前和干预后1年,我们进行了临床和神经学检查、脑磁共振成像和动脉粥样硬化生物标志物的实验室测试。结果。在基线时,所有个体在评估指标中都表现出促动脉粥样硬化的转变,主要是细胞外基质降解、炎症和动脉粥样硬化的标志物(包括骨保护素和铬粒蛋白А)。此外,我们建立了骨保护素水平与大多数高回声动脉粥样硬化斑块特征之间的直接相关性(r = 0.29;p 0.05)。一年后,在随访的支架动脉超声评估中没有发现再狭窄的迹象。在CAS后1年,我们发现骨保护素水平有显著变化(降至1.765 pg/mL [1.592;1.937);p 0.05)和嗜铬粒蛋白А(升高至31.3 g/L [13.9;90.7);p 0.05)。重新评估表明氮氧化物系统模式的变化之间存在关联,该模式趋于改善(NO升高至38.23 mol/L [32.95;43.51);P 0.001),以及动脉粥样硬化斑块形态和生物标志物特征的动脉粥样硬化保护转变。结论。对因有症状/无症状血流动力学意义显著的ICA狭窄而接受CAS治疗的患者进行为期1年的前瞻性观察显示,超声和血液粥样硬化生物标志物比率均发生了有利的动脉粥样硬化保护转变。这一转变导致随访期间没有脑动脉粥样硬化进展。这一过程可能是由嗜铬粒蛋白А和骨保护素介导的,需要从动脉粥样硬化的角度进一步研究。
{"title":"Assessment of Biomarker Profile in Patients Post Carotid Angioplasty and Stenting","authors":"М.М. Tanashyan, V. Annushkin, A. Raskurazhev, O. Lagoda, Аlla А. Shabalina, R. Medvedev, V. Shchipakin","doi":"10.54101/acen.2023.2.1","DOIUrl":"https://doi.org/10.54101/acen.2023.2.1","url":null,"abstract":"Introduction. Cardiovascular diseases are predominantly caused by atherosclerosis as a multifactorial chronic condition. Alterations in the hematological system and the blood vessel wall are considered as highly significant for onset and development of cerebrovascular disorders associated with atherosclerosis. Biomarkers as measurable indicators are to verify abnormal activity. \u0000Objective: to assess atherogenesis biomarkers in patients after carotid angioplasty and stenting (CAS) as associated with development of cerebrovascular disease. \u0000Materials and methods. We evaluated 50 individuals (50% men, 50% women; average age 65.4 6.4 years) with established cerebrovascular disease associated with brain atherosclerosis. All of them had hemodynamically significant abnormalities in the internal carotid artery (ICA) with both symptomatic (stenosis 60% and more) and asymptomatic (stenosis 70% and more) stenoses confirmed by duplex scanning of the brachiocephalic arteries. All patients underwent CAS as indicated. Before and 1 year after the intervention, we performed clinical and neurological examinations, brain magnetic resonance imaging, and laboratory tests of atherogenesis biomarkers. \u0000Results. At baseline, all the individuals demonstrated a pro-atherogenic shift in the assessed indicators, predominantly markers of extracellular matrix degradation, inflammation and atherogenesis (including osteoprotegerin and chromogranin А). Additionally, we established a direct correlation between osteoprotegerin levels and the characteristics of mostly hyperechoic atherosclerotic plaques (r = 0.29; p 0.05). A year later, no signs of restenosis were shown in follow-up ultrasound assessment of stented arteries in any patient. \u0000In 1 year post CAS, we found significant changes in the levels of osteoprotegerin (decrease to 1.765 pg/mL [1.592; 1.937]; p 0.05) and chromogranin А (elevation to 31.3 g/L [13.9; 90.7]; p 0.05). Re-assessment demonstrated association between changes in the pattern of the nitrogen oxide system, which tends to improve (NO elevation to 38.23 mol/L [32.95; 43.51]; p 0.001), and atheroprotective shift in the morphology of atherosclerotic plaques and biomarker profile. \u0000Conclusion. Prospective, 1-year long observation for patients who underwent CAS for symptomatic/asymptomatic hemodynamically significant ICA stenoses revealed favourable atheroprotective shift in both ultrasound and hematological atherogenesis biomarker ratio. This shift contributed to the absence of cerebral atherosclerosis progression during the follow-up. The process may be mediated by chromogranin А and osteoprotegerin, and their further research is needed from perspective of atherogenesis.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74452159","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}
引用次数: 0
Predictors of In-Hospital Mortality Among Patients with COVID-19 Related Stroke COVID-19相关脑卒中患者住院死亡率的预测因素
Q3 Multidisciplinary Pub Date : 2023-06-21 DOI: 10.54101/acen.2023.2.2
A. R. Rakhmatullin, M. Kutlubaev, A. T. Khayrullin
Introduction. COVID-19-related stroke is associated with a significantly higher mortality than COVID-19 or stroke alone. Mechanisms underlying the increased mortality of patients with stroke and COVID-19 should be thoroughly studied. Objective: to analyze predictors of hospital mortality associated with COVID-19-related stroke. Materials and methods. We retrospectively analyzed 1,386 cases of COVID-19-related stroke reported by an infectious diseases inpatient clinic in 2020. We studied clinical, laboratory, and instrumental parameters in patients with different outcomes. Logistic regression was used to identify independent predictors of mortality. Results. 539 (38.9%) patients died during their hospital stay, with 437 (38.0%) deaths from ischemic stroke and 102 (42.7%) deaths from hemorrhagic stroke (p = 0.0001). Independent predictors of mortality associated with COVID-19-related stroke included age, neurological deficit severity measured by NIHSS, COVID-19 severity, and laboratory parameters including white blood cell count, creatinine, glucose, and D-dimer blood levels. Discussion. The results of logistic regression analysis were able to explain only 41% of the variability in hospital deaths among patients with stroke associated with COVID-19. Conclusion. Hospital mortality in patients with COVID-19-related stroke is associated with severity of inflammatory response, impaired coagulation, age, neurological deficit severity, and somatic comorbidities.
介绍。COVID-19相关中风的死亡率明显高于COVID-19或单独中风。应深入研究卒中合并COVID-19患者死亡率增加的机制。目的:分析新型冠状病毒肺炎相关脑卒中住院死亡率的预测因素。材料和方法。回顾性分析某传染病门诊2020年报告的1386例新冠肺炎相关脑卒中病例。我们研究了不同结果患者的临床、实验室和仪器参数。使用逻辑回归来确定死亡率的独立预测因子。结果:539例(38.9%)患者在住院期间死亡,其中437例(38.0%)死于缺血性卒中,102例(42.7%)死于出血性卒中(p = 0.0001)。与COVID-19相关卒中相关的死亡率的独立预测因素包括年龄、NIHSS测量的神经功能缺陷严重程度、COVID-19严重程度和实验室参数,包括白细胞计数、肌酐、葡萄糖和d -二聚体血液水平。讨论。逻辑回归分析的结果仅能够解释与COVID-19相关的卒中患者住院死亡率的41%的变异性。结论。covid -19相关卒中患者的住院死亡率与炎症反应严重程度、凝血功能受损、年龄、神经功能缺损严重程度和躯体合并症有关。
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引用次数: 0
COVID-19 Features in Patients with Multiple Sclerosis: Main Approaches to Their Management, Treatment, and Vaccination 多发性硬化症患者的COVID-19特征:其管理、治疗和疫苗接种的主要途径
Q3 Multidisciplinary Pub Date : 2023-06-21 DOI: 10.54101/acen.2023.2.7
Valeriya A. Malko, G. Bisaga, M. Topuzova, I. Ternovykh, T. Alekseeva
The COVID-19 pandemic calls for correct and evidence-based decisions regarding management and treatment of patients with multiple sclerosis. Information on researches, clinical cases, and recommendations for treatment of such patients during the pandemic should be classified. We report COVID-19 features in patients with multiple sclerosis, risk factors for infection and development of severe disease. We also describe management strategies for multiple sclerosis: from relapse treatment to the selection of disease-modifying therapies focusing on patients safety. We analyze the latest observational and comparative studies, clinical cases of multiple sclerosis patients vaccination and demyelinating disease onset after COVID-19 or vaccination.
COVID-19大流行要求在多发性硬化症患者的管理和治疗方面做出正确和基于证据的决策。有关研究、临床病例和大流行期间治疗此类患者的建议的信息应分类。我们报告了多发性硬化症患者的COVID-19特征、感染的危险因素和严重疾病的发展。我们还描述了多发性硬化症的管理策略:从复发治疗到以患者安全为重点的疾病改善疗法的选择。我们分析最新的观察和比较研究、多发性硬化症患者接种疫苗和脱髓鞘病发病后或接种疫苗的临床病例。
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引用次数: 0
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Annals of Clinical and Experimental Neurology
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