CNS Neuroscience & Therapeutics最新文献_第9页

The Association Between Aspartate Transaminase to Alanine Transaminase Ratio and Perioperative Ischemic Stroke in Patients With Diabetes: A Retrospective Cohort Study 谷草转氨酶与丙氨酸转氨酶比值与糖尿病患者围手术期缺血性卒中的相关性：一项回顾性队列研究。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-01-21 DOI: 10.1111/cns.70223

Siyuan Liu, Binbin Wang, Libin Ma, Huikai Yang, Min Liu, Yuxiang Song, Zhikang Zhou, Jingsheng Lou, Daming Zhou, Jiangbei Cao, Yanhong Liu, Weidong Mi, Yulong Ma

Background

Patients with diabetes are at a high risk for perioperative ischemic stroke (PIS). The use of biomarkers to identify high-risk patients and predict PIS may provide considerable reference value in clinical decision-making. The aspartate transaminase/alanine transaminase ratio (De Ritis ratio) has been proven to be associated with specific diabetic complications. However, the association between the De Ritis ratio and PIS has not been evaluated in this population. This retrospective cohort study aimed to evaluate the association between the preoperative De Ritis ratio and PIS in patients with type 2 diabetes undergoing noncardiovascular surgery.

Methods

Data from surgical patients were collected from January 2008 to August 2019. A total of 27,643 patients with type 2 diabetes mellitus (DM) undergoing noncardiovascular surgery under general anesthesia were screened. The optimal De Ritis ratio cutoff value was identified using the receiver operating characteristic (ROC) curve. Logistic regression models were used to evaluate the association between the preoperative De Ritis ratio and PIS. Propensity score matching (PSM), sensitivity analyses, and subgroup analyses were performed to further validate the robustness of this association.

Results

A total of 151 patients experienced PIS. A De Ritis ratio ≥ 1.04 was associated with an elevated risk of PIS after adjusting for baseline characteristics (OR [95% CI]: 2.25 [1.59–3.21]; p < 0.001), intraoperative parameters (2.50 [1.80–3.49]; p < 0.001), and all confounding variables (2.29 [1.61–3.29]; p < 0.001). In the propensity score-matched cohort, the association between the De Ritis ratio and PIS remained significant (2.04 [1.38–3.05]; p < 0.001). These associations were also consistently maintained in the sensitivity and subgroup analyses.

Conclusions

An elevated De Ritis ratio is strongly associated with a higher risk of PIS in patients with type 2 DM undergoing noncardiovascular surgery. This may provide additional information on PIS risk assessment in patients with type 2 DM undergoing noncardiovascular surgery.

背景：糖尿病患者是围手术期缺血性卒中（PIS）的高危人群。利用生物标志物识别高危患者并预测PIS可能对临床决策提供相当大的参考价值。天冬氨酸转氨酶/丙氨酸转氨酶比值（De Ritis ratio）已被证实与特定的糖尿病并发症有关。然而，在这一人群中，De - Ritis比率与PIS之间的关系尚未得到评估。本回顾性队列研究旨在评估接受非心血管手术的2型糖尿病患者术前De - Ritis比率与PIS之间的关系。方法：收集2008年1月至2019年8月手术患者的数据。在全麻下接受非心血管手术的2型糖尿病（DM）患者共27,643例。采用受试者工作特征（ROC）曲线确定最佳德里斯比临界值。采用Logistic回归模型评估术前De - Ritis ratio与PIS之间的关系。进行倾向评分匹配（PSM）、敏感性分析和亚组分析以进一步验证这种关联的稳健性。结果：151例患者出现PIS。在调整基线特征后，De - Ritis ratio≥1.04与PIS风险升高相关(OR [95% CI]: 2.25 [1.59-3.21]；结论：在接受非心血管手术的2型糖尿病患者中，德炎比率升高与PIS的高风险密切相关。这可能为接受非心血管手术的2型糖尿病患者的PIS风险评估提供额外的信息。

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引用次数: 0

Modulating Anxiety-Like Behaviors in Neuropathic Pain: Role of Anterior Cingulate Cortex Astrocytes Activation 神经性疼痛中焦虑样行为的调节：前扣带皮层星形胶质细胞激活的作用。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-01-21 DOI: 10.1111/cns.70227

Qingqing Zhou, Qi Zhong, Zhuang Liu, Ziyue Zhao, Jie Wang, Zongze Zhang

Aims

The comorbidity of anxiety-like symptoms in neuropathic pain (NP) is a significant yet often overlooked health concern. Anxiety sufferers may have a lower tolerance for pain, but which is difficult to treat. Accumulating evidence suggests a strong link between astrocytes and the manifestation of NP with concurrent anxiety-like behaviors. And the anterior cingulate cortex (ACC) has emerged as a key player in pain modulation and related emotional processing. However, the complex mechanisms that astrocytes in ACC influence anxiety behavior in mouse models of NP remain largely unexplored.

Methods

Utilizing the traditional spared nerve injury (SNI) surgical model, we employed chemogenetic approaches, immunofluorescence, and western blot to investigate the functional significance and interactive dynamics between ACC astrocytes and excitatory neurons.

Results

Our results revealed that SNI surgery induces NP and delayed anxiety-like behaviors, accompanied by increased astrocyte activity in the ACC. Chemogenetic manipulation demonstrated that inhibiting astrocytes alleviates anxiety symptoms, while activating them exacerbates anxiety-like behaviors, affecting local excitatory neurons and synapse density. Direct manipulation of ACC excitatory neurons also significantly impacted anxiety-like behaviors.

Conclusion

Our results highlight the pivotal role of ACC astrocytes in modulating anxiety-like behavior, suggesting a novel therapeutic strategy for anxiety associated with NP by targeting astrocyte function.

目的：神经性疼痛（NP）中焦虑样症状的共病是一个重要但经常被忽视的健康问题。焦虑患者可能对疼痛的耐受力较低，但这很难治疗。越来越多的证据表明星形胶质细胞与NP的表现与并发的焦虑样行为之间存在密切的联系。前扣带皮层（ACC）在疼痛调节和相关情绪处理中起着关键作用。然而，ACC中的星形胶质细胞影响NP小鼠焦虑行为的复杂机制在很大程度上仍未被探索。方法：利用传统的SNI手术模型，采用化学发生、免疫荧光、western blot等方法研究ACC星形胶质细胞与兴奋性神经元的功能意义及相互作用动力学。结果：我们的研究结果显示SNI手术诱导NP和延迟焦虑样行为，并伴有ACC中星形胶质细胞活性增加。化学发生操作表明，抑制星形胶质细胞可缓解焦虑症状，而激活它们会加剧焦虑样行为，影响局部兴奋性神经元和突触密度。直接操纵ACC兴奋性神经元也显著影响焦虑样行为。结论：我们的研究结果突出了ACC星形胶质细胞在调节焦虑样行为中的关键作用，为靶向星形胶质细胞功能治疗NP相关焦虑提供了一种新的治疗策略。

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引用次数: 0

Evaluating Brain Activity in Patients With Chronic Disorders of Consciousness After Traumatic Brain Injury Using EEG Microstate Analysis During Hyperbaric Oxygen Therapy 高压氧治疗期间脑电图微状态分析评价创伤性脑损伤后慢性意识障碍患者的脑活动。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-01-20 DOI: 10.1111/cns.70220

Long Xu, Jiameng Wang, Cong Wang, Qianqian Ge, Ziqi Ren, Chen He, Yun Liu, Bo Wang, Yaling Liu, Lianbi Xue, Jianghong He, Xudong Zhao, Qiuhong Yu

Background

Hyperbaric oxygen (HBO) therapy is an efficacious intervention for patients with prolonged disorders of consciousness (pDOC). Electroencephalographic (EEG) microstate analysis can provide an assessment of the global state of the brain. Currently, the misdiagnosis rate of consciousness-level assessments in patients with pDOC is high. Therefore, we aimed to assess the consciousness levels and outcomes of patients by analyzing changes in EEG signals during HBO therapy.

Methods

EEG data were collected from 32 patients with traumatic brain injury before and after 20 min of HBO therapy. EEG data were obtained during HBO therapy sessions. Modified k-means clustering was used to segment EEG signals into microstates. A paired sample t test was used to compare the microstate characteristics before and during HBO therapy.

Results

The duration, occurrence, and coverage of microstate D significantly increased in the minimally conscious state (MCS) group after therapy. Significant increases in the same parameters were observed in microstate A among patients in the unresponsive wakefulness state group. Furthermore, patients with greater improvements in Coma Recovery Scale-Revised scores (i.e., improvements of more than three points) showed significant increases in the duration, occurrence, and coverage of microstate D. Both the MCS group and the improvement group presented significant increases in the duration, occurrence, and coverage of microstate D during therapy.

Conclusions

Microstate D may be associated with the recovery of consciousness levels in patients. This study verified the safety and feasibility of real-time EEG during HBO therapy for patients with pDOC. The changes in EEG microstate characteristics during HBO therapy can serve as a significant complement to electroencephalographic assessment indices for patients with pDOC and may be useful for predicting the recovery of consciousness levels.

背景：高压氧（HBO）治疗是延长性意识障碍（pDOC）患者的有效干预手段。脑电图（EEG）微观状态分析可以提供对大脑整体状态的评估。目前，pDOC患者意识水平评估的误诊率较高。因此，我们旨在通过分析HBO治疗过程中脑电图信号的变化来评估患者的意识水平和预后。方法：收集32例颅脑外伤患者HBO治疗前后20 min的脑电图资料。在HBO治疗期间获得脑电图数据。采用改进的k-means聚类方法对脑电信号进行微观状态分割。采用配对样本t检验比较HBO治疗前后患者的微状态特征。结果：微状态D在MCS组治疗后持续时间、发生率和覆盖范围均显著增加。在无反应清醒状态组的患者中，在微状态A中观察到相同参数的显著增加。此外，昏迷恢复量表修正评分改善较大（即改善3分以上）的患者在治疗期间微状态D的持续时间、发生次数和覆盖范围均显著增加。MCS组和改善组在治疗期间微状态D的持续时间、发生次数和覆盖范围均显著增加。结论：微状态D可能与患者意识水平的恢复有关。本研究验证了实时脑电图在pDOC患者HBO治疗期间的安全性和可行性。HBO治疗期间脑电图微状态特征的变化可作为pDOC患者脑电图评估指标的重要补充，并可用于预测患者意识水平的恢复。

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引用次数: 0

Correction to “Cinchonine and Cinchonidine Alleviate Cisplatin-Induced Ototoxicity by Regulating PI3K-AKT Signaling” 更正“Cinchonine和Cinchonidine通过调节PI3K-AKT信号减轻顺铂诱导的耳毒性”。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-01-20 DOI: 10.1111/cns.70228

D. Tang, X. Wang, J. Wu, Y. Li, C. Li, X. Qiao, L. Fan, Y. Chen, H. Zhu, Z. Zhang, and Y. He, “Cinchonine and Cinchonidine Alleviate Cisplatin-Induced Ototoxicity by Regulating PI3K-AKT Signaling,” CNS Neuroscience & Therapeutics 30, no. 2 (2024): e14403, https://doi.org/10.1111/cns.14403.

We apologize for this error.

引用次数: 0

Electroacupuncture Pretreatment Reduces Ischemic Brain Injury by Inhibiting the Lactate Production and Its Derived Protein Lactylation Formation 电针预处理通过抑制乳酸生成及其衍生蛋白乳酸化形成减少缺血性脑损伤。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-01-20 DOI: 10.1111/cns.70231

Xin-Ru Pan, Yao-Dan Zhang, Yuan-Hui Gan, Jia-Hang Zhang, Su-Jin Gao, Xiao-Shuang Feng, Jia-Xin Xie, Yu-Fei Wang, Xin-Xiao Zhang, Peng-Fei Wang, Shu-Guang Yu, Yong Tang, Xiao-Yi Xiong

Aim

Given that electroacupuncture (EA) pretreatment inhibits lactate production and lactate-derived lysine lactation (Kla) aggravates ischemic brain injury, we aimed to investigate whether the formation of Kla protein is involved in EA pretreatment to alleviate ischemic brain injury.

Methods

EA was performed on the Baihui acupoint (GV20) of male C57BL/6J mice before receiving the permanent middle cerebral artery occlusion (pMCAO) surgery. Western blot and immunofluorescent staining were used to observe neuronal survival, astrocyte activation, and protein Kla levels, and the lactate levels in ischemic brains were assayed with a commercial kit. TTC staining and neurological function scores are performed to evaluate the brain damage in mice.

Results

We found that the increased lactate content and protein Kla levels were significantly decreased in ischemic brain tissue of mice after receiving EA pretreatment, and accompanied by the reduction of astrocyte activation and neuronal injury and death. Meantime, we found that EA pretreatment was effective in reversing the worsening of ischemic brain injury caused by lactate supplementation. However, EA pretreatment did not further reduce the lactate content and protein Kla levels and ameliorate brain injury in ischemic stroke mice after inhibition of glycolysis.

Conclusion

Our study reveals that EA pretreatment reduced ischemic brain damage by inhibiting lactate production and its derived protein Kla formation in mice with ischemic stroke.

目的：鉴于电针（EA）预处理抑制乳酸生成，乳酸源性赖氨酸泌乳（Kla）加重缺血性脑损伤，我们旨在探讨Kla蛋白的形成是否参与电针预处理对缺血性脑损伤的缓解作用。方法：在C57BL/6J雄性小鼠永久性大脑中动脉闭塞（pMCAO）手术前，对其百会穴（GV20）进行电刺激。采用Western blot和免疫荧光染色法观察神经元存活、星形胶质细胞活化、蛋白Kla水平，并用商品化试剂盒检测缺血脑组织乳酸水平。采用TTC染色和神经功能评分评价小鼠脑损伤。结果：我们发现EA预处理后小鼠缺血脑组织乳酸含量和蛋白Kla水平明显降低，并伴有星形胶质细胞活化和神经元损伤死亡的减少。同时，我们发现EA预处理能有效逆转乳酸补充引起的缺血性脑损伤恶化。然而，EA预处理并没有进一步降低糖酵解抑制后缺血性脑卒中小鼠的乳酸含量和蛋白Kla水平，也没有改善脑损伤。结论：我们的研究表明，EA预处理通过抑制缺血性脑卒中小鼠乳酸生成及其衍生蛋白Kla的形成来减轻缺血性脑损伤。

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引用次数: 0

What We Know About TMEM175 in Parkinson's Disease

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-01-20 DOI: 10.1111/cns.70195

Jing Wang, Xuechun Sun, Lufeng Cheng, Meijie Qu, Chanyuan Zhang, Xueting Li, Lingyan Zhou

Background

Lysosome is a highly heterogeneous membranous organelle in eukaryotic cells, which regulates many physiological processes in the cell. Studies have found that lysosomal dysfunction disrupts cellular homeostasis and is associated with Parkinson's disease (PD). Transmembrane protein 175 (TMEM175) is a lysosomal cation channel whose activity is essential for lysosomal homeostasis. At present, it has been confirmed that TMEM175 is related to the pathogenesis of PD, but the relationship between the two remains unclear.

Aims

A thorough comprehension of the structure and function of TMEM175 would greatly contribute to elucidating the achievement of this objective. In this paper, the structure, composition, and function of TMEM175 and its relationship with PD will be reviewed.

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引用次数: 0

Single-Cell Insights Into Cellular Response in Abdominal Aortic Occlusion-Induced Hippocampal Injury 单细胞观察腹主动脉闭塞诱导的海马损伤的细胞反应。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-01-20 DOI: 10.1111/cns.70154

Changhong Ren, Ling Kui, Jun Xu, Fang Tong, Xiaojie Wang, Jianping Ma, Xiaomei Tian, Guoyun Wang, Feng-Yong Liu, Sijie Li, Xunming Ji

Objective

Ischemia–reperfusion of the abdominal aorta often results in damage to distant organs, such as the heart and brain. This cellular heterogeneity within affected tissues complicates the roles of specific cell subsets in abdominal aorta occlusion model (AAO) injury. However, cell type–specific molecular pathology in the hippocampus after ischemia is poorly understood.

Aims

In this study, we adopted a mouse AAO to investigate the single-cell transcriptome in the hippocampi in AAO mice.

Methods

Male C57BL/6 mice (8 weeks old) were used to create an AAO model, with animals divided into Sham and I/R groups. The I/R group was subjected to 2 h of ischemia followed by 24 h of reperfusion, after which hippocampal tissues were collected for single-cell RNA sequencing and histological analysis. Behavioral tests, including the Rotarod, Y-maze, and new object recognition tests, were performed daily for 28 days post-surgery to evaluate neurological function. A total of 62,624 cells were corresponding 7 cell types with neuronal, glial, and vascular lineages. We next analyzed cell-specific gene alterations in AAO mice and the function of these cell-specific Genes.

Results

AAO injury upregulated astrocyte and oligodendrocyte precursor cell (OPC) proportions (p-value < 0.05). Astrocytes showed unique gene expression related to neurogenesis and mRNA processing. Five distinct astrocyte subtypes emerged post-injury. OPCs exhibited enhanced synapse organization. Microglia activation and the elevated expression level of the epithelial cell oxidative phosphorylation protein–protein interaction (PPI) module indicate an inflammatory response and metabolic changes in response to AAO injury.

Conclusions

Our scRNA-seq analysis provides insights into transcriptional changes at the single-cell level in response to AAO-induced hippocampal injury. This study illustrates how the hippocampal region responds to such injury and identifies potential therapeutic targets for intervention, thereby paving the way for future research and treatment strategies.

目的：腹主动脉缺血再灌注常导致远端脏器如心、脑的损伤。受影响组织内的细胞异质性使特定细胞亚群在腹主动脉闭塞模型（AAO）损伤中的作用复杂化。然而，缺血后海马细胞类型特异性分子病理尚不清楚。目的：本研究采用小鼠AAO对AAO小鼠海马单细胞转录组进行研究。方法：采用雄性C57BL/6小鼠（8周龄）建立AAO模型，分为Sham组和I/R组。I/R组缺血2 h，再灌注24 h，取海马组织进行单细胞RNA测序和组织学分析。术后28天每天进行行为测试，包括Rotarod、y型迷宫和新物体识别测试，以评估神经功能。共有62,624个细胞对应于神经元、胶质和血管谱系的7种细胞类型。接下来，我们分析了AAO小鼠细胞特异性基因的改变以及这些细胞特异性基因的功能。结果：AAO损伤上调星形胶质细胞和少突胶质细胞前体细胞（OPC）比例（p值）。结论：我们的scRNA-seq分析提供了单细胞水平上AAO诱导的海马损伤的转录变化。这项研究阐明了海马区对这种损伤的反应，并确定了干预的潜在治疗靶点，从而为未来的研究和治疗策略铺平了道路。

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引用次数: 0

ADAR1 Promotes the Progression and Temozolomide Resistance of Glioma Through p62-Mediated Selective Autophagy ADAR1通过p62介导的选择性自噬促进胶质瘤的进展和替莫唑胺耐药性。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-01-18 DOI: 10.1111/cns.70168

Yuyan Zhang, Huiling Guo, Jiahao Bu, Weiwei Wang, Li Wang, Zhibo Liu, Yuning Qiu, Qimeng Wang, Lijuan Zhou, Xianzhi Liu, Liwei Ma, Jianwei Wei

Background

Resistance to temozolomide (TMZ) remains is an important cause of treatment failure in patients with glioblastoma multiforme (GBM). ADAR1, as a member of the ADAR family, plays an important role in cancer progression and chemotherapy resistance. However, the mechanism by which ADAR1 regulates GBM progression and TMZ resistance is still unclear.

Methods

We first constructed stable transfected strains in which ADAR1 was knocked down and overexpressed to investigate the effect of ADAR1 on the first-line glioma chemotherapy drug TMZ. Subsequently, we validated that ADAR1 induces autophagy activation and used autophagy inhibitors to suppress autophagy, demonstrating that ADAR1 enhances TMZ resistance through autophagy. We further knocked down p62 (SQSTM1) based on the overexpression of ADAR1, and the results showed that ADAR1 regulates selective autophagy through the p62 regulation. Finally, we demonstrated through mutations at both edited and nonedited sites that ADAR1 regulates selective autophagy in an edited dependent way.

Results

Further analysis showed that in the presence of TMZ, elevated ADAR1 promoted TMZ induced autophagy activation. Further research revealed that ADAR1 enhances TMZ resistance through p62-mediated selective autophagy. Further, ADAR1 regulates selective autophagy in an edited dependent way. Our results indicate a relationship between ADAR1 levels and the response of glioma patients to TMZ treatment.

Conclusions

We found that the expression of ADAR1 is upregulated in GBM and is associated with tumor grade and TMZ resistance. Elevated expression of ADAR1 predicts poor prognosis in GBM patients and promotes tumor growth in vivo or in vitro.

背景：替莫唑胺（TMZ）耐药性仍然是多形性胶质母细胞瘤（GBM）患者治疗失败的重要原因。ADAR1作为ADAR家族的一员，在癌症进展和化疗耐药中发挥重要作用。然而，ADAR1调控GBM进展和TMZ耐药的机制尚不清楚。方法：首先构建ADAR1被敲低和过表达的稳定转染菌株，研究ADAR1对胶质瘤一线化疗药物TMZ的影响。随后，我们验证了ADAR1诱导自噬激活，并使用自噬抑制剂抑制自噬，证明ADAR1通过自噬增强TMZ抗性。我们在ADAR1过表达的基础上进一步敲低p62 (SQSTM1)，结果表明ADAR1通过调控p62调控选择性自噬。最后，我们通过编辑和非编辑位点的突变证明，ADAR1以编辑依赖的方式调节选择性自噬。结果：进一步分析发现，在TMZ存在下，ADAR1升高可促进TMZ诱导的自噬激活。进一步研究发现ADAR1通过p62介导的选择性自噬增强TMZ抗性。此外，ADAR1以编辑依赖的方式调节选择性自噬。我们的研究结果表明ADAR1水平与胶质瘤患者对TMZ治疗的反应有关。结论：我们发现ADAR1在GBM中表达上调，并与肿瘤分级和TMZ耐药性有关。ADAR1表达升高预示GBM患者预后不良，促进肿瘤在体内或体外生长。

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引用次数: 0

CHOP-Mediated Disruption of Hippocampal Synaptic Plasticity and Neuronal Activity Contributes to Chronic Pain-Related Cognitive Deficits chop介导的海马突触可塑性和神经元活动的破坏有助于慢性疼痛相关的认知缺陷。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-01-16 DOI: 10.1111/cns.70160

Qingsheng Meng, Songxue Su, Lei Lei, Yubing Zhang, Jiabin Duan, Xiuhua Ren, Yihang Song, Xiaoyu Hu, Shiyue Chen, Weidong Zang, Zhen Zhang, Jing Cao

Objectives

Endoplasmic reticulum (ER) stress-induced protein homeostasis perturbation is a core pathological element in the pathogenesis of neurodegenerative diseases. This study aims to clarify the unique role played by C/EBP homologous protein (CHOP) as a biomarker of the unfolded protein response (UPR) in the etiology of chronic pain and related cognitive impairments following chronic constrictive nerve injury (CCI).

Methods

The memory capability following CCI was assessed utilizing the Morris water maze (MWM) and fear conditioning test (FCT). Activation of the UPR was quantified by assessing levels of CHOP and key ER stress sensors. The terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay and the levels of cleaved caspase-3 were utilized to assess apoptosis level. Synaptic plasticity was assessed via a modified Golgi-Cox staining method, and long-term potentiation (LTP) measurements were taken. Neuronal activity was determined by immunofluorescence and fiber photometry. Knockdown of CHOP and alleviation of ER stress were selectively induced by LV-Ddit3-shRNAs and the chemical chaperone 4-phenylbutyric acid (4-PBA), respectively.

Results

Mice subjected to CCI displayed enduring pain and cognitive impairments evident on Days 21–28 post-surgery. Following CCI, changes in the dorsal CA1 (dCA1) manifested as ER dilation, upregulation of CHOP and upstream signaling molecules, reduced dendritic spine density, and PSD95 levels, and impaired LTP. Additionally, the co-localization of CaMKIIα/c-Fos and CaMKIIα^dCA1-mediated calcium signaling was significantly reduced, while the activation of CaMKIIα was found to mitigate cognitive impairments in CCI mice. Selective knockdown of CHOP enhanced synaptic plasticity and CaMKIIα neuron activity, while 4-PBA treatment alleviated ER stress, synergistically improving cognitive deficits associated with chronic pain.

Conclusion

CCI-induced CHOP upregulation impairs dCA1 synaptic plasticity and neuronal activity, leading to chronic pain-related cognitive deficits.

目的：内质网应激引起的蛋白稳态紊乱是神经退行性疾病发病的核心病理因素。本研究旨在阐明C/EBP同源蛋白（CHOP）作为未折叠蛋白反应（UPR）的生物标志物在慢性缩窄性神经损伤（CCI）后慢性疼痛和相关认知障碍病因学中的独特作用。方法：采用Morris水迷宫（MWM）和恐惧条件反射测试（FCT）对CCI后的记忆能力进行评估。通过评估CHOP和关键内质网应力传感器的水平来量化UPR的激活。采用末端脱氧核苷酸转移酶（TdT） dUTP镍端标记法（TUNEL）和cleaved caspase-3水平评估细胞凋亡水平。采用改良的高尔基-考克斯染色法评估突触可塑性，并进行长期增强（LTP）测量。采用免疫荧光法和纤维光度法测定神经元活性。lv - ddit3 - shrna和化学伴侣4-苯基丁酸（4-PBA）分别选择性诱导CHOP的下调和内质网应激的缓解。结果：CCI小鼠在术后21-28天表现出明显的持续疼痛和认知障碍。CCI后，背侧CA1 （dCA1）的变化表现为内质网扩张，CHOP和上游信号分子上调，树突棘密度和PSD95水平降低，LTP受损。此外，CaMKIIα/c-Fos和CaMKIIα dca1介导的钙信号共定位显著降低，而CaMKIIα的激活可以减轻CCI小鼠的认知障碍。选择性敲低CHOP可增强突触可塑性和CaMKIIα神经元活性，而4-PBA治疗可缓解内质网应激，协同改善慢性疼痛相关的认知缺陷。结论：cci诱导的CHOP上调损害dCA1突触可塑性和神经元活性，导致慢性疼痛相关认知障碍。

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引用次数: 0

Is Overlain Display a Right Choice for AR Navigation? A Qualitative Study of Head-Mounted Augmented Reality Surgical Navigation on Accuracy for Large-Scale Clinical Deployment 重叠显示是AR导航的正确选择吗？头戴式增强现实手术导航对大规模临床部署准确性的定性研究。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-01-16 DOI: 10.1111/cns.70217

Jian Ye, Qingwen Chen, Tao Zhong, Jian Liu, Han Gao

Background

During the course of the past two decades, head-mounted augmented reality surgical navigation (HMARSN) systems have been increasingly employed in a variety of surgical specialties as a result of both advancements in augmented reality–related technologies and surgeons' desires to overcome some drawbacks inherent to conventional surgical navigation systems. In the present time, most experimental HMARSN systems adopt overlain display (OD) that overlay virtual models and planned routes of surgical tools on corresponding physical tissues, organs, lesions, and so forth, in a surgical field so as to provide surgeons with an intuitive and direct view to gain better hand–eye coordination as well as avoid attention shift and loss of sight (LOS), among other benefits during procedures. Yet, its system accuracy, which is the most crucial performance indicator of any surgical navigation system, is difficult to ascertain because it is highly subjective and user-dependent. Therefore, the aim of this study was to review presently available experimental OD HMARSN systems qualitatively, explore how their system accuracy is affected by overlain display, and find out if such systems are suited to large-scale clinical deployment.

Method

We searched PubMed and ScienceDirect with the following terms: head mounted augmented reality surgical navigation, and 445 records were returned in total. After screening and eligibility assessment, 60 papers were finally analyzed. Specifically, we focused on how their accuracies were defined and measured, as well as whether such accuracies are stable in clinical practice and competitive with corresponding commercially available systems.

Results and Conclusions

The primary findings are that the system accuracy of OD HMARSN systems is seriously affected by a transformation between the spaces of the user's eyes and the surgical field, because measurement of the transformation is heavily individualized and user-dependent. Additionally, the transformation itself is potentially subject to changes during surgical procedures, and hence unstable. Therefore, OD HMARSN systems are not suitable for large-scale clinical deployment.

背景：在过去的二十年中，由于增强现实相关技术的进步和外科医生希望克服传统手术导航系统固有的一些缺点，头戴式增强现实手术导航（HMARSN）系统越来越多地应用于各种外科专业。目前，大多数实验HMARSN系统采用重叠显示（overain display， OD），将手术工具的虚拟模型和规划路线叠加在手术区域内相应的物理组织、器官、病变等上，为外科医生提供直观、直接的观察，以获得更好的手眼协调，避免手术过程中的注意力转移和视力丧失等好处。然而，它的系统精度是任何手术导航系统最重要的性能指标，很难确定，因为它是高度主观和用户依赖的。因此，本研究的目的是定性地回顾目前可用的实验OD HMARSN系统，探讨重叠显示如何影响其系统精度，并找出这些系统是否适合大规模临床部署。方法：用头戴式增强现实外科导航检索PubMed和ScienceDirect，共检索到445条记录。经过筛选和合格性评估，最终对60篇论文进行分析。具体来说，我们关注的是如何定义和测量它们的准确性，以及这种准确性在临床实践中是否稳定，是否与相应的商业可用系统具有竞争力。结果和结论：主要发现OD HMARSN系统的系统精度受到用户眼睛空间和手术视野之间转换的严重影响，因为转换的测量是高度个性化和用户依赖的。此外，在手术过程中，变形本身可能会发生变化，因此不稳定。因此，OD HMARSN系统不适合大规模临床部署。

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引用次数: 0