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Dominant mechanism in spinal cord injury-induced immunodeficiency syndrome (SCI-IDS): sympathetic hyperreflexia. 脊髓损伤诱导免疫缺陷综合征(SCI-IDS)的主要机制:交感神经反射亢进。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-10-30 Print Date: 2024-04-25 DOI: 10.1515/revneuro-2023-0090
Ping Yang, Zhi-Qun Bian, Zhen-Bo Song, Cheng-Ying Yang, Li Wang, Zhong-Xiang Yao

Clinical studies have shown that individuals with spinal cord injury (SCI) are particularly susceptible to infectious diseases, resulting in a syndrome called SCI-induced immunodeficiency syndrome (SCI-IDS), which is the leading cause of death after SCI. It is believed that SCI-IDS is associated with exaggerated activation of sympathetic preganglionic neurons (SPNs). After SCI, disruption of bulbospinal projections from the medulla oblongata C1 neurons to the SPNs results in the loss of sympathetic inhibitory modulation from the brain and brainstem and the occurrence of abnormally high levels of spinal sympathetic reflexes (SSR), named sympathetic hyperreflexia. As the post-injury survival time lengthens, mass recruitment and anomalous sprouting of excitatory interneurons within the spinal cord result in increased SSR excitability, resulting in an excess sympathetic output that disrupts the immune response. Therefore, we first analyze the structural underpinnings of the spinal cord-sympathetic nervous system-immune system after SCI, then demonstrate the progress in highlighting mechanisms of SCI-IDS focusing on norepinephrine (NE)/Beta 2-adrenergic receptor (β2-AR) signal pathways, and summarize recent preclinical studies examining potential means such as regulating SSR and inhibiting β2-AR signal pathways to improve immune function after SCI. Finally, we present research perspectives such as to promote the effective regeneration of C1 neurons to rebuild the connection of C1 neurons with SPNs, to regulate excitable or inhibitory interneurons, and specifically to target β2-AR signal pathways to re-establish neuroimmune balance. These will help us design effective strategies to reverse post-SCI sympathetic hyperreflexia and improve the overall quality of life for individuals with SCI.

临床研究表明,脊髓损伤(SCI)患者特别容易感染传染病,导致一种名为SCI诱导免疫缺陷综合征(SCI-IDS)的综合征,这是SCI后死亡的主要原因。人们认为SCI-IDS与交感节前神经元(SPNs)的过度激活有关。SCI后,延髓C1神经元向SPN的延髓投射被破坏,导致大脑和脑干失去交感神经抑制性调节,并出现异常高水平的脊髓交感神经反射(SSR),称为交感神经反射亢进。随着损伤后存活时间的延长,脊髓内兴奋性中间神经元的大量募集和异常出芽导致SSR兴奋性增加,导致交感神经输出过多,破坏免疫反应。因此,我们首先分析了SCI后脊髓交感神经系统免疫系统的结构基础,然后展示了SCI-IDS在强调去甲肾上腺素(NE)/β2-肾上腺素能受体(β2-AR)信号通路机制方面的进展,并总结了最近的临床前研究,探讨了调节SSR和抑制β2-AR信号通路等改善SCI后免疫功能的潜在手段。最后,我们提出了一些研究前景,如促进C1神经元的有效再生,重建C1神经元与SPN的连接,调节可兴奋或抑制的中间神经元,特别是靶向β2-AR信号通路,重建神经免疫平衡。这些将有助于我们设计有效的策略来逆转SCI后交感神经反射亢进,并提高SCI患者的整体生活质量。
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引用次数: 0
Intracortical brain-computer interfaces for improved motor function: a systematic review. 改善运动功能的皮质内脑机接口:一项系统综述。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-10-17 Print Date: 2024-02-26 DOI: 10.1515/revneuro-2023-0077
Matthew W Holt, Eric C Robinson, Nathan A Shlobin, Jacob T Hanson, Ismail Bozkurt

In this systematic review, we address the status of intracortical brain-computer interfaces (iBCIs) applied to the motor cortex to improve function in patients with impaired motor ability. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Guidelines for Systematic Reviews. Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) and the Effective Public Health Practice Project (EPHPP) were used to assess bias and quality. Advances in iBCIs in the last two decades demonstrated the use of iBCI to activate limbs for functional tasks, achieve neural typing for communication, and other applications. However, the inconsistency of performance metrics employed by these studies suggests the need for standardization. Each study was a pilot clinical trial consisting of 1-4, majority male (64.28 %) participants, with most trials featuring participants treated for more than 12 months (55.55 %). The systems treated patients with various conditions: amyotrophic lateral sclerosis, stroke, spinocerebellar degeneration without cerebellar involvement, and spinal cord injury. All participants presented with tetraplegia at implantation and were implanted with microelectrode arrays via pneumatic insertion, with nearly all electrode locations solely at the precentral gyrus of the motor cortex (88.88 %). The development of iBCI devices using neural signals from the motor cortex to improve motor-impaired patients has enhanced the ability of these systems to return ability to their users. However, many milestones remain before these devices can prove their feasibility for recovery. This review summarizes the achievements and shortfalls of these systems and their respective trials.

在这篇系统综述中,我们讨论了应用于运动皮层以改善运动能力受损患者功能的皮层内脑机接口(iBCI)的现状。本研究遵循了《系统评价和荟萃分析首选报告项目(PRISMA)2020系统评价指南》。非随机干预研究中的偏倚风险(ROBINS-I)和有效公共卫生实践项目(EPHPP)用于评估偏倚和质量。iBCI在过去二十年中的进步证明了iBCI用于激活肢体执行功能任务、实现通信的神经类型以及其他应用。然而,这些研究所采用的绩效指标的不一致性表明了标准化的必要性。每项研究都是一项试点临床试验,由1-4名男性(64.28 %) 参与者,大多数试验的参与者接受了超过12个月的治疗(55.55 %). 该系统治疗各种疾病的患者:肌萎缩侧索硬化症、中风、无小脑受累的脊髓小脑变性和脊髓损伤。所有参与者在植入时都出现四肢瘫痪,并通过气动插入植入微电极阵列,几乎所有电极位置都仅位于运动皮层中央前回(88.88 %). iBCI设备的开发利用来自运动皮层的神经信号来改善运动受损患者,增强了这些系统向用户返回能力的能力。然而,在这些设备能够证明其恢复可行性之前,还有许多里程碑。本综述总结了这些系统的成就和不足及其各自的试验。
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引用次数: 0
Adult ADHD: it is old and new at the same time - what is it? 成人多动症:它是旧的,也是新的——它是什么?
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-10-11 Print Date: 2024-02-26 DOI: 10.1515/revneuro-2023-0071
Raly James Perez Custodio, Jan G Hengstler, Jae Hoon Cheong, Hee Jin Kim, Edmund Wascher, Stephan Getzmann

Even though the number of studies aiming to improve comprehension of ADHD pathology has increased in recent years, there still is an urgent need for more effective studies, particularly in understanding adult ADHD, both at preclinical and clinical levels, due to the increasing evidence that adult ADHD is highly distinct and a different entity from childhood ADHD. This review paper outlines the symptoms, diagnostics, and neurobiological mechanisms of ADHD, with emphasis on how adult ADHD could be different from childhood-onset. Data show a difference in the environmental, genetic, epigenetic, and brain structural changes, when combined, could greatly impact the behavioral presentations and the severity of ADHD in adults. Furthermore, a crucial aspect in the quest to fully understand this disorder could be through longitudinal analysis. In this way, we will determine if and how the pathology and pharmacology of ADHD change with age. This goal could revolutionize our understanding of the disorder and address the weaknesses in the current clinical classification systems, improving the characterization and validity of ADHD diagnosis, specifically those in adults.

尽管近年来旨在提高对多动症病理学理解的研究数量有所增加,但仍然迫切需要更有效的研究,特别是在临床前和临床水平上理解成人多动症,因为越来越多的证据表明,成人多动症与儿童多动症有着高度的区别和不同。本文概述了多动症的症状、诊断和神经生物学机制,重点介绍了成人多动症与儿童期多动症的区别。数据显示,环境、遗传、表观遗传学和大脑结构变化的差异,如果结合起来,可能会极大地影响成人多动症的行为表现和严重程度。此外,在寻求完全理解这种障碍的过程中,一个关键方面可以是通过纵向分析。通过这种方式,我们将确定多动症的病理学和药理学是否以及如何随着年龄的增长而变化。这一目标可能会彻底改变我们对多动症的理解,并解决当前临床分类系统中的弱点,提高多动症诊断的特征和有效性,特别是成人多动症诊断。
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引用次数: 0
Subjective, behavioral and neurobiological effects of cannabis and cannabinoids in social anxiety. 大麻和大麻素对社交焦虑的主观、行为和神经生物学影响。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-10-11 Print Date: 2024-02-26 DOI: 10.1515/revneuro-2023-0078
Bárbara Dos Anjos Rosário, Jéssica Alves Lemes, Maria Paula de Lima, Daniel Araki Ribeiro, Milena de Barros Viana

Social anxiety disorder (SAD) is a debilitating disorder, characterized by fear and anxiety in social situations. Evidence suggests that the levels of SAD are rising, in particularly after the COVID-19 pandemic. Serotonin and noradrenaline reuptake inhibitors and cognitive-behavioral therapy are effective treatments for SAD. Nevertheless, a significant number of patients do not respond well to these therapeutic options. During the last years, Cannabis and cannabinoid-containing products have been investigated for the treatment of different neuropsychiatric disorders. Nevertheless, their efficacy for the treatment of anxiety disorders is still a matter of debate. The purpose of this review was to investigate subjective, behavioral, and neurobiological effects of Cannabis and cannabinoids in social anxiety and SAD. A search in the PubMed database for articles published between the years of 2003-2023 was conducted. One hundred and seventeen (117) original studies were identified. After the exclusion criteria, eighteen (18) studies were selected. The studies investigated the effects of the cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in patients or healthy volunteers submitted to tasks that assessed social anxiety. Results showed that CBD decreases social anxiety, producing an inverted U-shaped curve, with anxiety measurements being reduced at intermediate doses administered orally (300-600 mg), but not at lower or higher doses. THC either reduces (lower doses, 6-7.5 mg) or increases (higher doses) social anxiety measurements. CBD attenuates the anxiogenic effects of THC. The effects of THC and CBD in anxiety are associated to the modulation of fronto-limbic regions. Further clinical trials, conducted with male and female patients and larger cohorts are still necessary to consolidate these results.

社交焦虑症(SAD)是一种使人衰弱的疾病,其特征是社交环境中的恐惧和焦虑。有证据表明,SAD水平正在上升,尤其是在新冠肺炎大流行之后。血清素和去甲肾上腺素再摄取抑制剂以及认知行为疗法是治疗SAD的有效方法。然而,相当多的患者对这些治疗方案反应不佳。在过去的几年里,大麻和含有大麻素的产品被研究用于治疗不同的神经精神疾病。尽管如此,它们治疗焦虑症的疗效仍然存在争议。本综述的目的是研究大麻和大麻素在社交焦虑和SAD中的主观、行为和神经生物学作用。在PubMed数据库中搜索2003-2023年间发表的文章。确定了一百一十七(117)项原始研究。在排除标准之后,选择了十八(18)项研究。这些研究调查了大麻素Δ9-四氢大麻酚(THC)和大麻二酚(CBD)对接受社交焦虑评估任务的患者或健康志愿者的影响。结果表明,CBD降低了社交焦虑,产生了一条倒U型曲线,口服中等剂量(300-600 mg),但不是以更低或更高的剂量。四氢大麻酚降低(较低剂量,6-7.5 mg)或增加(更高剂量)社交焦虑测量。CBD可减弱四氢大麻酚的致焦虑作用。四氢大麻酚和CBD在焦虑中的作用与额边缘区域的调节有关。仍有必要对男性和女性患者以及更大的队列进行进一步的临床试验,以巩固这些结果。
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引用次数: 0
Frontmatter 头版头条
3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-10-01 DOI: 10.1515/revneuro-2023-frontmatter7
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引用次数: 0
Understanding visual processing of motion: completing the picture using experimentally driven computational models of MT. 理解运动的视觉处理:使用实验驱动的MT计算模型完成图片。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-09-20 Print Date: 2024-04-25 DOI: 10.1515/revneuro-2023-0052
Parvin Zarei Eskikand, David B Grayden, Tatiana Kameneva, Anthony N Burkitt, Michael R Ibbotson

Computational modeling helps neuroscientists to integrate and explain experimental data obtained through neurophysiological and anatomical studies, thus providing a mechanism by which we can better understand and predict the principles of neural computation. Computational modeling of the neuronal pathways of the visual cortex has been successful in developing theories of biological motion processing. This review describes a range of computational models that have been inspired by neurophysiological experiments. Theories of local motion integration and pattern motion processing are presented, together with suggested neurophysiological experiments designed to test those hypotheses.

计算建模有助于神经科学家整合和解释通过神经生理学和解剖学研究获得的实验数据,从而提供一种我们可以更好地理解和预测神经计算原理的机制。视觉皮层神经元通路的计算建模在发展生物运动处理理论方面取得了成功。这篇综述描述了一系列受神经生理学实验启发的计算模型。介绍了局部运动积分和模式运动处理的理论,以及为验证这些假设而设计的神经生理学实验。
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引用次数: 0
Automated diagnosis of autism with artificial intelligence: State of the art. 人工智能自动诊断自闭症:最新技术。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-09-08 Print Date: 2024-02-26 DOI: 10.1515/revneuro-2023-0050
Amir Valizadeh, Mana Moassefi, Amin Nakhostin-Ansari, Soheil Heidari Some'eh, Hossein Hosseini-Asl, Mehrnush Saghab Torbati, Reyhaneh Aghajani, Zahra Maleki Ghorbani, Iman Menbari-Oskouie, Faezeh Aghajani, Alireza Mirzamohamadi, Mohammad Ghafouri, Shahriar Faghani, Amir Hossein Memari

Autism spectrum disorder (ASD) represents a panel of conditions that begin during the developmental period and result in impairments of personal, social, academic, or occupational functioning. Early diagnosis is directly related to a better prognosis. Unfortunately, the diagnosis of ASD requires a long and exhausting subjective process. We aimed to review the state of the art for automated autism diagnosis and recognition in this research. In February 2022, we searched multiple databases and sources of gray literature for eligible studies. We used an adapted version of the QUADAS-2 tool to assess the risk of bias in the studies. A brief report of the methods and results of each study is presented. Data were synthesized for each modality separately using the Split Component Synthesis (SCS) method. We assessed heterogeneity using the I 2 statistics and evaluated publication bias using trim and fill tests combined with ln DOR. Confidence in cumulative evidence was assessed using the GRADE approach for diagnostic studies. We included 344 studies from 186,020 participants (51,129 are estimated to be unique) for nine different modalities in this review, from which 232 reported sufficient data for meta-analysis. The area under the curve was in the range of 0.71-0.90 for all the modalities. The studies on EEG data provided the best accuracy, with the area under the curve ranging between 0.85 and 0.93. We found that the literature is rife with bias and methodological/reporting flaws. Recommendations are provided for future research to provide better studies and fill in the current knowledge gaps.

自闭症谱系障碍(ASD)是一种始于发育期并导致个人、社交、学习或职业功能障碍的疾病。早期诊断直接关系到更好的预后。遗憾的是,ASD 的诊断需要一个漫长而费力的主观过程。本研究旨在回顾自闭症自动诊断和识别的最新进展。2022 年 2 月,我们在多个数据库和灰色文献中搜索了符合条件的研究。我们使用改编版的 QUADAS-2 工具来评估研究的偏倚风险。本文简要报告了每项研究的方法和结果。我们采用拆分成分综合法(SCS)分别对每种方式的数据进行了综合。我们使用I 2统计量评估异质性,并使用修剪和填充检验结合ln DOR评估发表偏倚。我们采用诊断研究的 GRADE 方法评估了累积证据的可信度。我们在本综述中纳入了九种不同方式的 344 项研究,涉及 186,020 名参与者(估计有 51,129 名参与者是唯一的),其中 232 项研究报告了足够的数据用于荟萃分析。所有模式的曲线下面积均在 0.71-0.90 之间。关于脑电图数据的研究提供了最好的准确性,曲线下面积在 0.85 至 0.93 之间。我们发现,文献中充斥着偏见和方法/报告缺陷。我们为今后的研究提出了建议,以提供更好的研究并填补目前的知识空白。
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引用次数: 0
"Brain-breath" interactions: respiration-timing-dependent impact on functional brain networks and beyond. "大脑与呼吸 "之间的相互作用:呼吸计时对大脑功能网络及其他方面的影响。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-09-01 Print Date: 2024-02-26 DOI: 10.1515/revneuro-2023-0062
Nozomu H Nakamura, Yoshitaka Oku, Masaki Fukunaga

Breathing is a natural daily action that one cannot do without, and it sensitively and intensely changes under various situations. What if this essential act of breathing can impact our overall well-being? Recent studies have demonstrated that breathing oscillations couple with higher brain functions, i.e., perception, motor actions, and cognition. Moreover, the timing of breathing, a phase transition from exhalation to inhalation, modulates specific cortical activity and accuracy in cognitive tasks. To determine possible respiratory roles in attentional and memory processes and functional neural networks, we discussed how breathing interacts with the brain that are measured by electrophysiology and functional neuroimaging: (i) respiration-dependent modulation of mental health and cognition; (ii) respiratory rhythm generation and respiratory pontomedullary networks in the brainstem; (iii) respiration-dependent effects on specific brainstem regions and functional neural networks (e.g., glutamatergic PreBötzinger complex neurons, GABAergic parafacial neurons, adrenergic C1 neurons, parabrachial nucleus, locus coeruleus, temporoparietal junction, default-mode network, ventral attention network, and cingulo-opercular salience network); and (iv) a potential application of breathing manipulation in mental health care. These outlines and considerations of "brain-breath" interactions lead to a better understanding of the interoceptive and cognitive mechanisms that underlie brain-body interactions in health conditions and in stress-related and neuropsychiatric disorders.

呼吸是一个人每天都离不开的自然动作,它在各种情况下都会发生敏感而强烈的变化。如果呼吸这一基本动作会影响我们的整体健康呢?最新研究表明,呼吸振荡与大脑的高级功能(即感知、运动和认知)相关联。此外,呼吸的时间(从呼气到吸气的阶段转换)会调节特定的大脑皮层活动和认知任务的准确性。为了确定呼吸在注意力和记忆过程以及功能神经网络中可能发挥的作用,我们讨论了呼吸如何与大脑相互作用,并通过电生理学和功能神经影像学进行了测量:(i) 呼吸对心理健康和认知的调控;(ii) 呼吸节奏的产生和脑干中的呼吸髓质网络;(iii) 呼吸对特定脑干区域和功能神经网络的影响(例如,谷氨酸能PreB、谷氨酸能前伯兴格复合神经元、GABA 能面旁神经元、肾上腺素能 C1 神经元、腕旁核、皮质室、颞顶交界处、缺省模式网络、腹侧注意网络和脑瓢虫显著性网络)的影响;以及 (iv) 呼吸调节在心理保健中的潜在应用。这些关于 "大脑-呼吸 "相互作用的概述和考虑有助于更好地理解在健康状况下以及在压力相关和神经精神疾病中大脑-身体相互作用的互感和认知机制。
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引用次数: 0
In vivo C6 glioma models: an update and a guide toward a more effective preclinical evaluation of potential anti-glioblastoma drugs. 体内C6胶质瘤模型:更新并指导对潜在抗胶质母细胞瘤药物进行更有效的临床前评估。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-09-01 Print Date: 2024-02-26 DOI: 10.1515/revneuro-2023-0067
Safura Pournajaf, Nastaran Afsordeh, Mohammad Hossein Pourgholami

Glioblastoma multiform (GBM) is the most common primary brain tumor with a poor prognosis and few therapeutic choices. In vivo, tumor models are useful for enhancing knowledge of underlying GBM pathology and developing more effective therapies/agents at the preclinical level, as they recapitulate human brain tumors. The C6 glioma cell line has been one of the most widely used cell lines in neuro-oncology research as they produce tumors that share the most similarities with human GBM regarding genetic, invasion, and expansion profiles and characteristics. This review provides an overview of the distinctive features and the different animal models produced by the C6 cell line. We also highlight specific applications of various C6 in vivo models according to the purpose of the study and offer some technical notes for more convenient/repeatable modeling. This work also includes novel findings discovered in our laboratory, which would further enhance the feasibility of the model in preclinical GBM investigations.

多形性胶质母细胞瘤(GBM)是最常见的原发性脑肿瘤,预后较差,治疗选择很少。体内肿瘤模型能再现人类脑肿瘤,有助于增强对多形性胶质母细胞瘤潜在病理的了解,并在临床前开发出更有效的疗法/制剂。C6 胶质瘤细胞系是神经肿瘤学研究中使用最广泛的细胞系之一,因为它们产生的肿瘤在遗传、侵袭和扩增特征方面与人类 GBM 最为相似。本综述概述了 C6 细胞系的显著特征和不同的动物模型。我们还根据研究目的强调了各种 C6 体内模型的具体应用,并为更方便/可重复建模提供了一些技术说明。这项工作还包括我们实验室发现的新发现,这些发现将进一步提高该模型在临床前 GBM 研究中的可行性。
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引用次数: 0
An update to pain management after spinal cord injury: from pharmacology to circRNAs. 脊髓损伤后疼痛管理的最新进展:从药理学到环状rna。
IF 4.1 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-08-28 DOI: 10.1515/revneuro-2022-0089
Graciela L Mazzone, María F Coronel, Miranda Mladinic, Cynthia Sámano

Neuropathic pain (NP) following a spinal cord injury (SCI) is often hard to control and therapies should be focused on the physical, psychological, behavioral, social, and environmental factors that may contribute to chronic sensory symptoms. Novel therapeutic treatments for NP management should be based on the combination of pharmacological and nonpharmacological options. Some of them are addressed in this review with a focus on mechanisms and novel treatments. Several reports demonstrated an aberrant expression of non-coding RNAs (ncRNAs) that may represent key regulatory factors with a crucial role in the pathophysiology of NP and as potential diagnostic biomarkers. This review analyses the latest evidence for cellular and molecular mechanisms associated with the role of circular RNAs (circRNAs) in the management of pain after SCI. Advantages in the use of circRNA are their stability (up to 48 h), and specificity as sponges of different miRNAs related to SCI and nerve injury. The present review discusses novel data about deregulated circRNAs (up or downregulated) that sponge miRNAs, and promote cellular and molecular interactions with mRNAs and proteins. This data support the concept that circRNAs could be considered as novel potential therapeutic targets for NP management especially after spinal cord injuries.

脊髓损伤(SCI)后的神经性疼痛(NP)通常难以控制,治疗应侧重于可能导致慢性感觉症状的生理、心理、行为、社会和环境因素。NP管理的新治疗方法应基于药物和非药物选择的结合。本文对其中的一些问题进行了综述,重点介绍了机制和新的治疗方法。一些报告表明,非编码rna (ncRNAs)的异常表达可能代表了在NP病理生理中起关键作用的关键调节因子,并作为潜在的诊断生物标志物。这篇综述分析了与环状rna (circRNAs)在脊髓损伤后疼痛管理中的作用相关的细胞和分子机制的最新证据。使用circRNA的优势在于其稳定性(可达48小时),以及作为与脊髓损伤和神经损伤相关的不同mirna海绵的特异性。本综述讨论了关于释放环状rna(上调或下调)的新数据,这些环状rna会吸收miRNAs,并促进细胞和分子与mrna和蛋白质的相互作用。这些数据支持circRNAs可以被视为NP治疗的新的潜在治疗靶点,特别是在脊髓损伤后。
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引用次数: 0
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Reviews in the Neurosciences
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