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Carthamin yellow attenuates brain injury in a neonatal rat model of ischemic-hypoxic encephalopathy by inhibiting neuronal ferroptosis in the hippocampus. 在缺血缺氧性脑病新生大鼠模型中,卡他明黄通过抑制海马神经元的铁突变减轻脑损伤。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2023-12-31 eCollection Date: 2023-01-01 DOI: 10.1515/tnsci-2022-0331
Yuanyu Zhou, Yuebin Wang, Xiaoqing Wu, Junjie Wu, Jianhui Yan, Wei Su

Hypoxic-ischemic encephalopathy (HIE) is a common neurological disorder characterized by ischemia and hypoxia in the perinatal period, which seriously affects the growth and development of newborns. To date, there is no specific drug for the treatment of HIE. Previous studies have shown that ferroptosis plays an important role in the pathogenesis of HIE. Carthamin yellow (CY) is believed to have antioxidant and anti-inflammatory effects. However, no studies have reported the role of CY in ferroptosis in HIE in vivo until now. The aim of this study was to investigate the effect and mechanism of CY on HIE in vivo and to provide an experimental basis for the clinical treatment of HIE. The results demonstrated that CY increased the expression of NeuN in the neonatal rat hypoxic-ischemic brain damage (HIBD) model. Further exploration revealed that CY increased the expression of glutathione peroxidase 4 and ferritin heavy chain 1 while it decreased the expression of PTGS2 and ACSL2. Moreover, CY decreased malondialdehyde expression and increased superoxide dismutase and glutathione expression in vivo. The findings also indicated that CY downregulated the expression of Nrf2 and Keap-1. In conclusion, this study demonstrated that CY attenuated brain injury in an experimental HIBD model, potentially by alleviating hippocampal neuronal ferroptosis through inhibition of the Nrf2/Keap-1 signaling pathway. These findings provide a novel therapeutic strategy for the clinical treatment of HIE.

缺氧缺血性脑病(HIE)是一种常见的神经系统疾病,其特点是围产期缺血缺氧,严重影响新生儿的生长发育。迄今为止,还没有治疗 HIE 的特效药物。以往的研究表明,高铁血症在 HIE 的发病机制中起着重要作用。卡他明黄(CY)被认为具有抗氧化和抗炎作用。然而,迄今为止还没有研究报道 CY 在 HIE 体内铁蛋白沉积中的作用。本研究旨在探讨 CY 对体内 HIE 的影响和机制,为临床治疗 HIE 提供实验依据。结果表明,在新生大鼠缺氧缺血性脑损伤(HIBD)模型中,CY能增加NeuN的表达。进一步研究发现,CY能增加谷胱甘肽过氧化物酶4和铁蛋白重链1的表达,同时降低PTGS2和ACSL2的表达。此外,CY 还能降低丙二醛的表达,增加超氧化物歧化酶和谷胱甘肽的表达。研究结果还表明,CY 下调了 Nrf2 和 Keap-1 的表达。总之,本研究表明,CY 可通过抑制 Nrf2/Keap-1 信号通路减轻海马神经元铁突变,从而减轻实验性 HIBD 模型的脑损伤。这些发现为临床治疗 HIE 提供了一种新的治疗策略。
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引用次数: 0
Myeloarchitectonic maps of the human cerebral cortex registered to surface and sections of a standard atlas brain. 根据标准地图集大脑表面和切片绘制的人类大脑皮层髓质结构图。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2023-12-26 eCollection Date: 2023-01-01 DOI: 10.1515/tnsci-2022-0325
Juergen K Mai, Milan Majtanik

C. and O. Vogt had set up a research program with the aim of establishing a detailed cartography of the medullary fiber distribution of the human brain. As part of this program, around 200 cortical fields were differentiated based on their myeloarchitectural characteristics and mapped with regard to their exact location in the isocortex. The typical features were graphically documented and classified by a sophisticated linguistic coding. Their results have only recently received adequate attention and applications. The reasons for the revival of this spectrum of their research include interest in the myeloarchitecture of the cortex as a differentiating feature of the cortex architecture and function, as well as the importance for advanced imaging methodologies, particularly tractography and molecular imaging. Here, we describe our approach to exploit the original work of the Vogts and their co-workers to construct a myeloarchitectonic map that is referenced to the Atlas of the Human Brain (AHB) in standard space. We developed a semi-automatic pipeline for processing and integrating the various original maps into a single coherent map. To optimize the precision of the registration between the published maps and the AHB, we augmented the maps with topographic landmarks of the brains that were originally analyzed. Registration of all maps into the AHB opened several possibilities. First, for the majority of the fields, multiple maps from different authors are available, which allows for sophisticated statistical integration, for example, unification with a label-fusion technique. Second, each field in the myeloarchitectonic surface map can be visualized on the myelin-stained cross-section of the AHB at the best possible correspondence. The features of each field can be correlated with the fiber-stained cross-sections in the AHB and with the extensive published materials from the Vogt school and, if necessary, corrected. Third, mapping to the AHB allows the relationship between fiber characteristics of the cortex and the subcortex to be examined. Fourth, the cytoarchitectonic maps from Brodmann and von Economo and Koskinas, which are also registered to the AHB, can be compared. This option allows the study of the correspondence between cyto- and myeloarchitecture in each field. Finally, by using our "stripe" technology - where any other feature registered to the same space can be directly compared owing to the linear and parallel representation of the correlated cortex segments - this map becomes part of a multidimensional co-registration platform.

C.和O.沃格特制定了一项研究计划,旨在绘制人脑髓质纤维分布的详细地图。作为该计划的一部分,大约 200 个皮质区域根据其髓质结构特征进行了区分,并绘制了它们在等皮层中的确切位置图。典型特征以图形记录下来,并通过复杂的语言编码进行分类。他们的研究成果直到最近才得到足够的重视和应用。他们的这一研究领域重获新生的原因包括:人们对皮层髓质结构作为皮层结构和功能区分特征的兴趣,以及对先进成像方法,特别是束成像和分子成像的重视。在此,我们介绍了我们利用 Vogts 及其合作者的原创性工作来构建髓质结构图的方法,该图以标准空间中的《人脑图谱》(AHB)为参照。我们开发了一个半自动管道,用于处理各种原始地图并将其整合为一个单一的连贯地图。为了优化已发布地图与 AHB 之间的配准精度,我们在地图上添加了最初分析的大脑的地形地标。将所有地图注册到 AHB 中提供了几种可能性。首先,对于大多数字段来说,不同作者的多幅地图都是可用的,这样就可以进行复杂的统计整合,例如使用标签融合技术进行统一。其次,髓鞘结构表面图中的每个字段都可以在髓鞘染色的 AHB 截面上以最佳的对应关系进行可视化。每个区域的特征都可以与 AHB 纤维染色横截面以及沃格特学派出版的大量资料进行关联,并在必要时进行修正。第三,映射到 AHB 可以检查皮层和皮层下纤维特征之间的关系。第四,布罗德曼(Brodmann)、冯-伊科诺姆(von Economo)和科斯基纳斯(Koskinas)的细胞结构图也被登记到 AHB 上,可以进行比较。通过这种方法可以研究每个领域中细胞和髓质结构之间的对应关系。最后,通过使用我们的 "条纹 "技术--由于相关皮层片段的线性和平行表示,在同一空间注册的任何其他特征都可以直接进行比较--该地图成为多维共同注册平台的一部分。
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引用次数: 0
Preoperatively administered single dose of dexketoprofen decreases pain intensity on the first 5 days after craniotomy: A single-centre placebo-controlled, randomized trial. 术前服用单剂量右酮洛芬可降低开颅手术后头 5 天的疼痛强度:单中心安慰剂对照随机试验。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2023-12-16 eCollection Date: 2023-01-01 DOI: 10.1515/tnsci-2022-0323
Éva Simon, Csaba Csipkés, Dániel Andráskó, Veronika Kovács, Zoltán Szabó-Maák, Béla Tankó, Gyula Buchholcz, Béla Fülesdi, Csilla Molnár

Background and purpose: Headache attributed to craniotomy is an underestimated and under-treated condition. Previous studies confirmed the efficacy of preemptive analgesia with non-steroidal anti-inflammatory agents. The aim of the present work was to test the hypothesis of whether a single preoperatively administered dose of dexketoprofen (DEX) has the potency to decrease postcraniotomy headache (PCH) as compared to placebo (PL).

Patients and methods: This is a single-centre, randomized, PL-controlled trial comparing the effect of a single oral dose of 25 mg DEX to PL on the intensity of PCH. Patients undergoing craniotomy were randomly allocated to DEX and PL groups. Patients rated their actual and worst daily pain using visual analogue scale (VAS) scores during intrahospital treatment (0-5 days) and 30 and 90 days postoperatively.

Results: Two hundred patients were included. DEX decreased the worst daily pain intensity in the first 24 h only; the 5-days cumulative score of actual pain was 9.7 ± 7.9 cm for the DEX group and 12.6 ± 10.5 cm for the PL group, respectively (p = 0.03). This difference disappeared in the late, 30-, and 90-day follow-up period. No differences in VAS scores could be detected in supra- and infratentorial cases among the DEX and PL groups.

Conclusions: A single preoperative dose of 25 mg of DEX slightly decreases the intensity of PCH in the first 5 days after craniotomy but it does not have an effect on chronic headaches and postoperative analgesic requirements.

背景和目的:开颅手术引起的头痛是一种被低估和治疗不足的病症。之前的研究证实了使用非甾体类抗炎药物进行术前镇痛的疗效。本研究的目的是检验以下假设:与安慰剂(PL)相比,术前单次给药右酮洛芬(DEX)是否能有效减轻开颅术后头痛(PCH):这是一项单中心、随机、安慰剂对照试验,比较单次口服 25 毫克 DEX 和安慰剂对 PCH 强度的影响。接受开颅手术的患者被随机分配到DEX组和PL组。患者在院内治疗期间(0-5天)以及术后30天和90天内使用视觉模拟量表(VAS)对其实际疼痛和最严重的日常疼痛进行评分:结果:共纳入 200 名患者。DEX仅在最初的24小时内降低了最严重的日常疼痛强度;DEX组和PL组5天的实际疼痛累积评分分别为9.7 ± 7.9 cm和12.6 ± 10.5 cm(P = 0.03)。这一差异在后期、30 天和 90 天的随访中消失。DEX组和PL组的上腹部和下腹部病例的VAS评分没有差异:结论:术前单次服用 25 毫克 DEX 可轻微降低开颅手术后头 5 天的 PCH 强度,但对慢性头痛和术后镇痛需求没有影响。
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引用次数: 0
Nanopharmacology as a new approach to treat neuroinflammatory disorders. 纳米药理学是治疗神经炎症性疾病的新方法。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2023-12-16 eCollection Date: 2023-01-01 DOI: 10.1515/tnsci-2022-0328
Sebastián García Menéndez, Walter Manucha

Neuroinflammation, a complex process involving the activation of microglia, astrocytes, and other immune cells in the brain, plays a role in neurodegeneration and psychiatric disorders. Current therapeutic strategies for neuroinflammation are limited, necessitating the development of improved approaches. Nanopharmacology offers unprecedented opportunities to access and treat neuroinflammatory disorders at the brain level. Nanoscaffolds can target specific cells or tissues and protect drugs from degradation or elimination, making them ideal candidates for treating neurodegenerative and psychiatric diseases. Recent advancements in nanoparticle development have enabled the targeting of microglia, astrocytes, and other immune cells in the brain, reducing neuroinflammation and protecting neurons from injury. Nanoparticles targeting specific neurons have also been developed. Clinical trials are in progress to evaluate the safety and efficacy of nano drugs for treating neuroinflammatory, neurodegenerative, and psychiatric diseases. The successful development of these nanodrugs holds immense promise for treating these devastating and increasingly prevalent conditions. On the other hand, several limitations and unanswered questions remain. First, the long-term effects of nanoparticles on the brain need to be thoroughly investigated to ensure their safety. Second, optimizing the targeting and delivery of nanoparticles to specific brain regions remains a challenge. Understanding the complex interplay between nanoparticles and the brain's immune system is crucial for developing effective nanotherapies. Despite these limitations, nanopharmacology presents a transformative approach to treating neuroinflammatory disorders. Future research should address the aforementioned limitations and further elucidate the mechanisms of nanoparticle-mediated therapy. The successful development of safe and effective nanodrugs can revolutionize the treatment of neuroinflammatory disorders, alleviating the suffering of millions.

神经炎症是大脑中涉及小胶质细胞、星形胶质细胞和其他免疫细胞激活的一个复杂过程,在神经变性和精神疾病中扮演着重要角色。目前针对神经炎症的治疗策略有限,因此有必要开发出更好的方法。纳米药理学提供了前所未有的机会,在大脑水平上获取和治疗神经炎症性疾病。纳米支架可以靶向特定细胞或组织,保护药物不被降解或清除,是治疗神经退行性疾病和精神疾病的理想选择。纳米粒子开发的最新进展使其能够靶向大脑中的小胶质细胞、星形胶质细胞和其他免疫细胞,从而减少神经炎症并保护神经元免受损伤。针对特定神经元的纳米粒子也已研制成功。目前正在进行临床试验,以评估纳米药物治疗神经炎症、神经退行性疾病和精神疾病的安全性和有效性。这些纳米药物的成功开发为治疗这些破坏性和日益普遍的疾病带来了巨大希望。另一方面,仍存在一些局限性和悬而未决的问题。首先,需要彻底研究纳米颗粒对大脑的长期影响,以确保其安全性。其次,优化纳米粒子的靶向性并将其输送到特定脑区仍然是一项挑战。了解纳米粒子与大脑免疫系统之间复杂的相互作用对于开发有效的纳米疗法至关重要。尽管存在这些局限性,但纳米药理学为治疗神经炎症性疾病提供了一种变革性的方法。未来的研究应解决上述局限性,并进一步阐明纳米粒子介导的治疗机制。安全有效的纳米药物的成功开发可彻底改变神经炎症性疾病的治疗方法,减轻数百万人的痛苦。
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引用次数: 0
EGCG promotes the sensory function recovery in rats after dorsal root crush injury by upregulating KAT6A and inhibiting pyroptosis. EGCG可通过上调KAT6A和抑制脓毒症促进大鼠背根挤压伤后的感觉功能恢复。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2023-12-14 eCollection Date: 2023-01-01 DOI: 10.1515/tnsci-2022-0326
Jianjun Wang, Zuer Yu, Yichun Hu, Fuyu Li, Xiaoyu Huang, Xiangyue Zhao, Yaqi Tang, Shujuan Fang, Yinjuan Tang

Dorsal root injury usually leads to irreversible sensory function loss and lacks effective treatments. (-)-epigallocatechin-3-gallate (EGCG) is reported to exert neuroprotective roles in the nervous systems. However, the function of EGCG in treating dorsal root injury remains unclear. Hence, we built the dorsal root crush injury (DRCI) rat model to be treated with EGCG, followed by the western blot, Enzyme-linked immunosorbent assay, and sensory behavior tests. We observed that EGCG can upregulate the Lysine acetyltransferase 6A (KAT6A) level and inhibit the pyroptosis, indicated by downregulated gasdermin-D, caspase-1, and interleukin 18 protein levels, and alleviate the neuropathic pain, indicated by the decreased paw withdraw threshold in Plantar test and decreased paw withdraw latency in von Frey test, and downregulated calcitonin gene-related peptide, nerve growth factor, and c-Fos protein levels. But EGCG cannot alleviate the neuropathic pain when the KAT6A was inhibited by CTX-0124143 and pyroptosis was activated by Miltirone. These combined results indicated that EGCG can promote the sensory function recovery in rats after DRCI via upregulating KAT6A and inhibiting pyroptosis, laying the foundation for EGCG to be a novel candidate for the treatment of dorsal root injury.

背根损伤通常会导致不可逆的感觉功能丧失,而且缺乏有效的治疗方法。(据报道,(-)-表没食子儿茶素-3-棓酸盐(EGCG)对神经系统具有保护作用。然而,EGCG 在治疗背根损伤方面的功能仍不清楚。因此,我们建立了背根挤压伤(DRCI)大鼠模型,用EGCG对其进行治疗,然后进行Western印迹、酶联免疫吸附试验和感觉行为试验。我们观察到,EGCG能上调赖氨酸乙酰转移酶6A(KAT6A)水平,抑制热蛋白沉积,表现为gasdermin-D、caspase-1和白细胞介素18蛋白水平下调;缓解神经病理性疼痛,表现为Plantar试验中爪抽出阈值降低,von Frey试验中爪抽出潜伏期缩短,降钙素基因相关肽、神经生长因子和c-Fos蛋白水平下调。但是,当 CTX-0124143 抑制 KAT6A 和 Miltirone 激活热变态反应时,EGCG 并不能缓解神经病理性疼痛。这些综合结果表明,EGCG可通过上调KAT6A和抑制热蛋白沉积促进背根损伤后大鼠感觉功能的恢复,为EGCG成为治疗背根损伤的新型候选药物奠定了基础。
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引用次数: 0
Predicting functional outcome in acute ischemic stroke patients after endovascular treatment by machine learning. 用机器学习预测急性缺血性脑卒中患者血管内治疗后的功能结局。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2023-11-27 eCollection Date: 2023-01-01 DOI: 10.1515/tnsci-2022-0324
Zhenxing Liu, Renwei Zhang, Keni Ouyang, Botong Hou, Qi Cai, Yu Xie, Yumin Liu

Background: Endovascular therapy (EVT) was the standard treatment for acute ischemic stroke with large vessel occlusion. Prognosis after EVT is always a major concern. Here, we aimed to explore a predictive model for patients after EVT.

Method: A total of 156 patients were retrospectively enrolled. The primary outcome was functional dependence (defined as a 90-day modified Rankin Scale score ≤ 2). Least absolute shrinkage and selection operator and univariate logistic regression were used to select predictive factors. Various machine learning algorithms, including multivariate logistic regression, linear discriminant analysis, support vector machine, k-nearest neighbors, and decision tree algorithms, were applied to construct prognostic models.

Result: Six predictive factors were selected, namely, age, baseline National Institute of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early CT (ASPECT) score, modified thrombolysis in cerebral infarction score, symptomatic intracerebral hemorrhage (sICH), and complications (pulmonary infection, gastrointestinal bleeding, and cardiovascular events). Based on these variables, various models were constructed and showed good discrimination. Finally, a nomogram was constructed by multivariate logistic regression and showed a good performance.

Conclusion: Our nomogram, which was composed of age, baseline NIHSS score, ASPECT score, recanalization status, sICH, and complications, showed a very good performance in predicting outcome after EVT.

背景:血管内治疗(EVT)是急性缺血性脑卒中合并大血管闭塞的标准治疗方法。EVT后的预后一直是主要关注的问题。在这里,我们旨在探索EVT患者的预测模型。方法:回顾性纳入156例患者。主要结局为功能依赖(定义为90天修正Rankin量表评分≤2)。最小绝对收缩、选择算子和单变量逻辑回归用于选择预测因素。各种机器学习算法,包括多元逻辑回归、线性判别分析、支持向量机、k近邻和决策树算法,被用于构建预测模型。结果:选取6个预测因素,分别为年龄、美国国立卫生研究院卒中量表(NIHSS)基线评分、阿尔伯塔卒中计划早期CT (ASPECT)评分、脑梗死改良溶栓评分、症状性脑出血(siich)、并发症(肺部感染、胃肠道出血、心血管事件)。基于这些变量,构建了各种模型,并表现出良好的判别性。最后,通过多元逻辑回归构造了一个nomogram,并取得了良好的效果。结论:我们的nomogram由年龄、基线NIHSS评分、ASPECT评分、再通状态、siich和并发症组成,对EVT的预后有很好的预测作用。
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引用次数: 0
PPARα agonist fenofibrate prevents postoperative cognitive dysfunction by enhancing fatty acid oxidation in mice. PPARα激动剂非诺贝特通过增强小鼠脂肪酸氧化来预防术后认知功能障碍。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2023-11-15 eCollection Date: 2023-01-01 DOI: 10.1515/tnsci-2022-0317
Tiantian Liu, Xinlu Chen, Ziqi Wei, Xue Han, Yujia Liu, Zhengliang Ma, Tianjiao Xia, Xiaoping Gu

Background: Due to high rates of incidence and disability, postoperative cognitive dysfunction (POCD) currently receives a lot of clinical attention. Disturbance of fatty acid oxidation is a potential pathophysiological manifestation underlying POCD. Peroxisome proliferator-activated receptor α (PPARα) is a significant transcription factor of fatty acid oxidation that facilitates the transfer of fatty acids into the mitochondria for oxidation. The potential role of PPARα intervention in POCD warrants consideration.

Objective: The present study is aimed to investigate whether PPARα agonist fenofibrate (FF) could protect long-term isoflurane anesthesia-induced POCD model and to explore the potential underlying function of fatty acid oxidation in the process.

Methods: We established the POCD model via 6 h long-term isoflurane anesthesia in vivo with C57BL/6J mice and in vitro with N2a cells. Cells and mice were pretreated with PPARα agonist FF before anesthesia, after which fatty acid oxidation and cognitive function were assessed. The level of fatty acid oxidation-related proteins was determined using western blotting. The contextual fear conditioning test was utilized to evaluate mice's learning and memory.

Results: Our results showed that 6 h long-term isoflurane anesthesia induced contextual memory damage in mice, accompanied by decreases of fatty acid oxidation-related proteins (peroxisome proliferator-activated receptor γ coactivator 1α, carnitine palmitoyltransferase 1A, and PPARα) both in the hippocampus of POCD mice and in N2a cells. In the N2a cell model, pretreatment of PPARα agonist FF led to the upregulation of fatty acid oxidation-related proteins. In vivo results showed that preconditioned FF reached similar effects. More crucially, FF has been shown to reduce cognitive damage in mice after long-term isoflurane anesthesia. Additionally, our data showed that after blocking fatty acid oxidation by Etomoxir, FF failed to protect cognitive function from long-term isoflurane anesthesia.

Conclusions: Pretreatment of PPARα agonist FF can protect against long-term isoflurane anesthesia-induced POCD by enhancing fatty acid oxidation.

背景:术后认知功能障碍(POCD)由于其高发病率和致残率,目前受到了临床的广泛关注。脂肪酸氧化障碍是POCD潜在的病理生理表现。过氧化物酶体增殖体激活受体α (PPARα)是脂肪酸氧化的重要转录因子,促进脂肪酸转移到线粒体氧化。PPARα干预POCD的潜在作用值得考虑。目的:研究PPARα激动剂非诺贝特(非诺贝特,FF)是否对长期异氟醚麻醉诱导的POCD模型具有保护作用,并探讨脂肪酸氧化在此过程中的潜在作用。方法:采用长时间异氟醚麻醉C57BL/6J小鼠体内和N2a细胞体外建立POCD模型。在麻醉前用PPARα激动剂FF对细胞和小鼠进行预处理,然后评估脂肪酸氧化和认知功能。western blotting检测脂肪酸氧化相关蛋白水平。采用情境恐惧条件反射法评价小鼠的学习记忆能力。结果:我们的研究结果表明,长时间异氟醚麻醉可引起小鼠情境记忆损伤,并伴有POCD小鼠海马和N2a细胞中脂肪酸氧化相关蛋白(过氧化物酶体增殖体激活受体γ共激活因子1α、肉碱棕榈酰基转移酶1A和PPARα)的减少。在N2a细胞模型中,预处理PPARα激动剂FF导致脂肪酸氧化相关蛋白上调。体内实验结果表明,预处理后的FF也达到了类似的效果。更重要的是,FF已被证明可以减少长期异氟醚麻醉后小鼠的认知损伤。此外,我们的数据显示,在用依托莫西阻断脂肪酸氧化后,FF不能保护长期异氟醚麻醉后的认知功能。结论:PPARα激动剂FF预处理可通过增强脂肪酸氧化作用,保护长期异氟醚麻醉诱导的POCD。
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引用次数: 0
Evaluation of the improvement of walking ability in patients with spinal cord injury using lower limb rehabilitation robots based on data science. 基于数据科学的下肢康复机器人对脊髓损伤患者行走能力改善的评价
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2023-11-11 eCollection Date: 2023-01-01 DOI: 10.1515/tnsci-2022-0320
Hui Zhao, Jingyi Yang, Jie Yang, Hongying Jiang, Yecai Qin, Qian Lei

Spinal cord injury (SCI) is a serious disabling injury, and the main factors causing SCI in patients include car accidents, falls from heights, as well as heavy blows and falls. These factors can all cause spinal cord compression or even complete rupture. After SCI, problems with the movement, balance, and walking ability of the lower limbs are most common, and SCI can cause abnormalities in patient's movement, sensation, and other aspects. Therefore, in the treatment of SCI, it is necessary to strengthen the rehabilitation training (RT) of patients based on data science to improve their motor ability and play a positive role in the recovery of their walking ability. This article used lower limb rehabilitation robot (LLRR) to improve the walking ability of SCI patients and applied them to SCI rehabilitation. The purpose is to improve the limb movement function of patients by imitating and assisting their limb movements, thereby achieving pain relief and muscle strength enhancement and promoting rehabilitation. The experimental results showed that the functional ambulation category (FAC) scale scores of Group A and Group B were 0.79 and 0.81, respectively, in the first 10 weeks of the experiment. After 10 weeks of the experiment, the FAC scores of Group A and Group B were 2.42 and 4.36, respectively. After the experiment, the FAC score of Group B was much higher than that of Group A, indicating that Group B was more effective in improving patients' walking ability compared to Group A. This also indicated that LLRR rehabilitation training can enhance the walking ability of SCI patients.

脊髓损伤(Spinal cord injury, SCI)是一种严重的致残性损伤,造成患者脊髓损伤的主要因素包括车祸、高空坠落、重击、摔伤等。这些因素都可能导致脊髓受压甚至完全断裂。脊髓损伤后,下肢运动、平衡和行走能力的问题最为常见,脊髓损伤可导致患者运动、感觉等方面的异常。因此,在脊髓损伤的治疗中,有必要加强基于数据科学的患者康复训练(RT),以提高患者的运动能力,对其行走能力的恢复起到积极的作用。本文利用下肢康复机器人(LLRR)提高SCI患者的行走能力,并将其应用于SCI康复。目的是通过模仿和辅助患者的肢体运动,改善患者的肢体运动功能,从而达到缓解疼痛,增强肌肉力量,促进康复的目的。实验结果显示,实验前10周,A组和B组的功能行走类别(FAC)量表得分分别为0.79和0.81。实验10周后,A组和B组FAC评分分别为2.42和4.36。实验结束后,B组的FAC评分远高于A组,说明B组在改善患者行走能力方面比A组更有效。这也说明LLRR康复训练可以增强SCI患者的行走能力。
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引用次数: 0
Long-term sevoflurane exposure relieves stress-enhanced fear learning and anxiety in PTSD mice. 长期接触七氟醚可以缓解创伤后应激障碍小鼠的压力增强的恐惧学习和焦虑。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2023-10-28 eCollection Date: 2023-01-01 DOI: 10.1515/tnsci-2022-0313
Ying Du, Minhui Xu, Yan Su, Yujia Liu, Yiming Zhou, Xiaoping Gu, Tianjiao Xia

Objectives: Post-traumatic stress disorder (PTSD) is characterized by recurrent episodes of severe anxiety after exposure to traumatic events. It is believed that these episodes are triggered at least in part by environmental stimuli associated with the precipitating trauma through classical conditioning, termed conditioned fear. However, traditional methods of conditioned fear memory extinction are frequently ineffective for PTSD treatment due to the contribution of non-associative sensitization caused by trauma. Anesthetics have shown promise for treating various psychiatric diseases such as depression.

Methods: In this study, we examined if the inhaled anesthetic sevoflurane can suppress stress-enhanced fear learning (SEFL) in PTSD model mice. Model mice exposed to 2.4% sevoflurane for 6 h exhibited reduced freezing time and behavioral anxiety compared to sham-treated model mice. To explore the underlying mechanisms, we evaluated the regional expression levels of glucocorticoid receptors (GRs), cannabinoid CB1 receptors (CB1Rs), D1 dopamine receptors (D1Rs), and D2 dopamine receptors (D2Rs).

Results: We verified that both GR and CB1R were significantly upregulated in the hippocampus, amygdaloid nucleus, and prefrontal cortex (PFC) of model mice, while D1R and D2R were downregulated. All of these expression changes were partially normalized in the PFC by 6 h but not with 2 h sevoflurane exposure.

Conclusions: These results showed that sevoflurane exposure following traumatic events may be an effective treatment for PTSD.

目的:创伤后应激障碍(PTSD)的特点是暴露于创伤事件后反复出现严重焦虑。据信,这些发作至少部分是由环境刺激引发的,这些环境刺激通过经典的条件反射(称为条件反射恐惧)引发创伤。然而,传统的条件性恐惧记忆消除方法对于创伤后应激障碍的治疗往往是无效的,因为创伤引起的非联想致敏作用。麻醉剂已显示出治疗抑郁症等各种精神疾病的前景。方法:在本研究中,我们检测了吸入麻醉剂七氟醚是否能抑制创伤后应激障碍模型小鼠的应激增强恐惧学习(SEFL)。模型小鼠暴露于2.4%七氟醚6天 与假手术处理的模型小鼠相比,h表现出冷冻时间和行为焦虑减少。为了探索潜在的机制,我们评估了糖皮质激素受体(GR)、大麻素CB1受体(CB1Rs)、D1多巴胺受体(D1Rs)和D2多巴胺受体(D2Rs)的区域表达水平,而D1R和D2R被下调。所有这些表达变化在PFC中被6 h,但不带2 h七氟醚暴露。结论:这些结果表明,创伤后七氟醚暴露可能是治疗创伤后应激障碍的有效方法。
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引用次数: 0
Cdk5 activation promotes Cos-7 cells transition towards neuronal-like cells. Cdk5激活促进Cos-7细胞向神经元样细胞过渡。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2023-10-25 eCollection Date: 2023-01-01 DOI: 10.1515/tnsci-2022-0318
Li Bao, Xiao-Mei Lan, Guo-Qing Zhang, Xi Bao, Bo Li, Dan-Na Ma, Hong-Yan Luo, Shi-Lu Cao, Shun-Yao Liu, E Jing, Jian-Zhong Zhang, Ya-Li Zheng

Objectives: Cyclin-dependent kinase 5 (Cdk5) activity is specifically active in neurogenesis, and Cdk5 and neocortical neurons migration related biomarker are expressed in Cos-7 cells. However, the function of Cdk5 on the transformation of immortalized Cos-7 cells into neuronal-like cells is not clear.

Methods: Cdk5 kinase activity was measured by [γ-32P] ATP and p81 phosphocellulose pads based method. The expression of neuron liker markers was evaluated by immunofluorescence, real-time PCR, Western blot, and Elisa.

Results: P35 overexpression upregulated Cdk5 kinase activity in Cos-7 cells. p35 mediated Cdk5 expression promoted the generation of nerite-like outgrowth. Compared with the empty vector, p35-induced Cdk5 activation resulted in time-dependent increase in neuron-like marker, including Tau, NF-H, NF-H&M, and TuJ1. Tau-5 and NF-M exhibited increased expression at 48 h while TuJ1 was only detectable after 96 h in p35 expressed Cos-7 cells. Additionally, the neural cell biomarkers exhibited well colocation with p35 proteins. Next-generation RNA sequence showed that p35 overexpression significantly upregulated the level of nerve growth factor (NGF). Gene set enrichment analysis showed significant enrichment of multiple neuron development pathways and increased NGF expression after p35 overexpression.

Conclusion: p35-mediated Cdk5 activation promotes the transformation of immortalized Cos-7 cells into neuronal-like cells by upregulating NGF level.

目的:细胞周期蛋白依赖性激酶5(Cdk5)活性在神经发生中具有特异性活性,并且Cdk5和新皮质神经元迁移相关生物标志物在Cos-7细胞中表达。然而,Cdk5对永生化的Cos-7细胞转化为神经元样细胞的作用尚不清楚。方法:采用[γ-32P]ATP和p81磷酸纤维素垫法测定Cdk5激酶活性。通过免疫荧光、实时PCR、Western印迹和Elisa评估神经元样标记物的表达。结果:P35过表达上调了Cos-7细胞中Cdk5激酶的活性。p35介导的Cdk5表达促进了苦苣苔样生长物的产生。与空载体相比,p35诱导的Cdk5激活导致神经元样标记物的时间依赖性增加,包括Tau、NF-H、NF-H&M和TuJ1。Tau-5和NF-M在48 h,而TuJ1仅在96 h在p35表达的Cos-7细胞中表达。此外,神经细胞生物标志物与p35蛋白表现出良好的共定位。下一代RNA序列显示p35过表达显著上调神经生长因子(NGF)水平。基因集富集分析显示,p35过表达后,多种神经元发育途径显著富集,NGF表达增加。结论:p35介导的Cdk5激活通过上调NGF水平促进永生化Cos-7细胞向神经元样细胞转化。
{"title":"Cdk5 activation promotes Cos-7 cells transition towards neuronal-like cells.","authors":"Li Bao,&nbsp;Xiao-Mei Lan,&nbsp;Guo-Qing Zhang,&nbsp;Xi Bao,&nbsp;Bo Li,&nbsp;Dan-Na Ma,&nbsp;Hong-Yan Luo,&nbsp;Shi-Lu Cao,&nbsp;Shun-Yao Liu,&nbsp;E Jing,&nbsp;Jian-Zhong Zhang,&nbsp;Ya-Li Zheng","doi":"10.1515/tnsci-2022-0318","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0318","url":null,"abstract":"<p><strong>Objectives: </strong>Cyclin-dependent kinase 5 (Cdk5) activity is specifically active in neurogenesis, and Cdk5 and neocortical neurons migration related biomarker are expressed in Cos-7 cells. However, the function of Cdk5 on the transformation of immortalized Cos-7 cells into neuronal-like cells is not clear.</p><p><strong>Methods: </strong>Cdk5 kinase activity was measured by [γ-<sup>32</sup>P] ATP and p81 phosphocellulose pads based method. The expression of neuron liker markers was evaluated by immunofluorescence, real-time PCR, Western blot, and Elisa.</p><p><strong>Results: </strong>P35 overexpression upregulated Cdk5 kinase activity in Cos-7 cells. p35 mediated Cdk5 expression promoted the generation of nerite-like outgrowth. Compared with the empty vector, p35-induced Cdk5 activation resulted in time-dependent increase in neuron-like marker, including Tau, NF-H, NF-H&M, and TuJ1. Tau-5 and NF-M exhibited increased expression at 48 h while TuJ1 was only detectable after 96 h in p35 expressed Cos-7 cells. Additionally, the neural cell biomarkers exhibited well colocation with p35 proteins. Next-generation RNA sequence showed that p35 overexpression significantly upregulated the level of nerve growth factor (NGF). Gene set enrichment analysis showed significant enrichment of multiple neuron development pathways and increased NGF expression after p35 overexpression.</p><p><strong>Conclusion: </strong>p35-mediated Cdk5 activation promotes the transformation of immortalized Cos-7 cells into neuronal-like cells by upregulating NGF level.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"14 1","pages":"20220318"},"PeriodicalIF":2.1,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Translational Neuroscience
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