Experimental Neurology最新文献_第3页

β-1, 3-galactosyltransferase 2 promotes cerebral angiogenesis and neurological recovery during the ischemic repair phase through glycosylation modification of TGF-βR(II)/ALK1 β- 1,3 -半乳糖转移酶2通过TGF-βR(II)/ALK1的糖基化修饰促进缺血修复期脑血管生成和神经系统恢复

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology

Pub Date : 2026-01-19 DOI: 10.1016/j.expneurol.2026.115651

Chang Liu , Yao Ma , Jiachen Li , Yunhao Xu , Meixuan Li , Hong Li , Zongze Li , Zhanyou Wang , Jia Liang , Peng Wang

β-1,3-galactosyltransferase 2 (B3galt2) has been increasingly recognized as an essential mediator in the pathogenesis of ischemic stroke (IS); nonetheless, its exact functional role has not been fully elucidated. This research aimed to clarify the regulatory mechanisms by which B3galt2 influences cerebral angiogenesis during the repair phase following ischemic injury. A mouse model of cerebral ischemia/reperfusion (I/R) injury was generated by subjecting animals to 1-h middle cerebral artery occlusion (MCAO), succeeded by reperfusion for varying time intervals. Recombinant human B3galt2 (rh-B3galt2) was administered intranasally beginning on day one post-injury and continued until tissue collection. Experimental outcomes revealed that rh-B3galt2 substantially diminished brain atrophy and enhanced neurological recovery during the repair phase of ischemia. Furthermore, rh-B3galt2 facilitated angiogenesis through increased expression of vascular endothelial growth factor A (VEGFA) and the tight junction proteins, occludin and claudin 5. Moreover, rh-B3galt2 activated the TGF-βR(II)/ALK1/Smad1/5 pathway. The galactosylation levels of TGF-βR(II) and ALK1 were increased after rh-B3galt2 treatment, suggesting that B3galt2 may regulate TGF-βR(II) and ALK1 through glycosylation modification. Moreover, the advantageous impacts of rh-B3galt2 on reducing brain atrophy and alleviating neurological deficits were reversed upon treatment with the ALK1 inhibitor, ML347. ML347 also counteracted the angiogenic promotion induced by rh-B3galt2, demonstrating that inhibition of ALK1 abolishes the protective benefits mediated by rh-B3galt2. Collectively, the results indicated that rh-B3galt2 significantly promotes angiogenesis and neurological function recovery during the cerebral ischemic repair stage, likely by regulating TGF-βR(II)/ALK1/Smad1/5 signaling pathway through glycosylation modification.

β-1,3-半乳糖转移酶2 （B3galt2）越来越被认为是缺血性卒中（IS）发病机制的重要介质；然而，其确切的功能作用尚未完全阐明。本研究旨在阐明B3galt2在缺血性损伤修复阶段影响脑血管新生的调控机制。采用大脑中动脉阻断（MCAO） 1h，再灌注不同时间间隔的方法，建立脑缺血再灌注（I/R）损伤小鼠模型。重组人B3galt2 （rh-B3galt2）从损伤后第一天开始经鼻给药，一直持续到组织收集。实验结果显示，在缺血修复阶段，rh-B3galt2显著减少脑萎缩，促进神经恢复。此外，rh-B3galt2通过增加血管内皮生长因子A （VEGFA）和紧密连接蛋白occludin和claudin 5的表达促进血管生成。此外，rh-B3galt2激活了TGF-βR(II)/ALK1/Smad1/5通路。rh-B3galt2处理后TGF-βR（II）和ALK1半乳糖基化水平升高，提示B3galt2可能通过糖基化修饰调节TGF-βR（II）和ALK1。此外，rh-B3galt2在减少脑萎缩和减轻神经功能缺陷方面的有利作用在使用ALK1抑制剂ML347治疗后被逆转。ML347还抵消了rh-B3galt2诱导的血管生成促进作用，表明对ALK1的抑制消除了rh-B3galt2介导的保护作用。综上所述，rh-B3galt2可能通过糖基化修饰调控TGF-βR(II)/ALK1/Smad1/5信号通路，显著促进脑缺血修复阶段血管生成和神经功能恢复。

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引用次数: 0

Long-term dietary interventions fail to mitigate functional connectivity loss and cognitive decline in the TgF344-AD rat model of Alzheimer's disease 在TgF344-AD大鼠阿尔茨海默病模型中，长期饮食干预不能减轻功能连接丧失和认知能力下降

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology

Pub Date : 2026-01-14 DOI: 10.1016/j.expneurol.2026.115647

Judith R.A. van Rooij , Monica van den Berg , Manoy Van Vosselen , Elke Calus , Tamara Vasilkovska , Lauren Kosten , Ignace Van Spilbeeck , Johan Van Audekerke , Debby Van Dam , Daniele Bertoglio , Mohit H. Adhikari , Marleen Verhoye

Short-term caloric restriction (CR) and resveratrol (Rsv) supplementation have shown potential in preserving brain function in aging and neurodegenerative diseases such as AD. However, there is a lack of knowledge regarding the potential benefits of long-term CR or Rsv on brain health in context of AD. Therefore, we aimed to assess the effects of short-term (1 month) CR and Rsv administration on resting-state functional connectivity (rs-FC), as well as the effect of long-term (8 months) CR or Rsv supplementation on rs-FC, spatial memory, amyloid burden, and neuroinflammation in male and female TgF344-AD (Tg) and wild-type (WT) rats. In Tg rats, short-term CR decreased rs-FC in female rats, while long-term CR decreased rs-FC and modestly improved spatial memory in male rats. Long-term CR and Rsv altered regional amyloid burden, and CR decreased IBA-1 in males without affecting GFAP. Overall, long-term CR and Rsv failed to mitigate FC loss and cognition, underscoring the potentially limited impact of these dietary interventions in AD.

短期热量限制（CR）和白藜芦醇（Rsv）补充剂已显示出在衰老和神经退行性疾病（如AD）中保持脑功能的潜力。然而，关于长期CR或Rsv对AD患者大脑健康的潜在益处，目前还缺乏相关知识。因此，我们旨在评估短期（1个月）CR和Rsv给药对静息状态功能连通性（rs-FC）的影响，以及长期（8个月）CR或Rsv补充对雄性和雌性TgF344-AD （Tg）和野生型（WT）大鼠rs-FC、空间记忆、淀粉样蛋白负担和神经炎症的影响。在Tg大鼠中，短期CR降低雌性大鼠的rs-FC，而长期CR降低雄性大鼠的rs-FC并适度改善空间记忆。长期CR和Rsv改变了区域淀粉样蛋白负荷，CR降低了男性的IBA-1，但不影响GFAP。总体而言，长期CR和Rsv未能减轻FC损失和认知，强调了这些饮食干预对AD的潜在有限影响。

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引用次数: 0

A mouse model for cerebral/cortical visual impairment (CVI) impairs vision and disrupts the spatial frequency tuning of neurons in visual cortex 脑/皮质视觉障碍（CVI）小鼠模型损害视觉并破坏视觉皮层神经元的空间频率调谐。

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology

Pub Date : 2026-01-14 DOI: 10.1016/j.expneurol.2026.115648

Dana K. Oakes , Cecilia A. Attaway , Wenxin Zeng , Jun Cai , William Guido , Aaron W. McGee

Cerebral/cortical visual impairment (CVI) is a visual disorder often associated with perinatal hypoxic injury. The pathophysiology of CVI is poorly understood in part because of the lack of an animal model. Here we developed a murine model of CVI from existing rodent early postnatal hypoxia models for periventricular leukomalacia. Exposure to hypoxia during the equivalent to the human third trimester did not perturb gross motor function but caused severe impairments in binocular depth perception and visual acuity measured with behavioral assays. Impaired vision was associated with normal retinal function assessed with electroretinograms, but reduced size of the visual thalamus, and aberrant tuning for spatial frequency by populations of excitatory neurons in primary visual cortex calculated from in vivo calcium imaging experiments. This murine model of CVI provides a framework for triangulating circuit deficits with the severity of visual impairment and testing potential therapeutic interventions.

脑/皮质视觉障碍（CVI）是一种视觉障碍，通常与围产期缺氧损伤有关。由于缺乏动物模型，对CVI的病理生理学知之甚少。在这里，我们从现有的啮齿动物出生后早期心室周围白质软化缺氧模型中建立了小鼠CVI模型。在相当于人类妊娠晚期的缺氧环境中，大肌肉运动功能没有受到干扰，但双眼深度感知和视觉灵敏度受到严重损害。视力受损与视网膜电图评估的正常视网膜功能有关，但视丘脑尺寸减小，并且从体内钙成像实验中计算出初级视觉皮层兴奋性神经元群体对空间频率的异常调节。这种小鼠CVI模型为三角测量电路缺陷与视觉损伤的严重程度和测试潜在的治疗干预提供了一个框架。

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引用次数: 0

The metabolic reprogramming of lactate in the nervous system 乳酸盐在神经系统中的代谢重编程

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology

Pub Date : 2026-01-14 DOI: 10.1016/j.expneurol.2026.115643

Yu Gu, Botao Zhang, Chunyan Lei, Yanjiao Guan, Binger Fan, Wenyan Xu, Ansong Jin, Qionghua Deng, Ruolong Xue, Xinglong Yang, Xiaoyan Zhu

Lactate, a critical energetic substrate and signaling molecule in the central nervous system (CNS), plays a pivotal role in maintaining neurophysiological homeostasis and driving the pathogenesis of neurodegenerative disorders through metabolic reprogramming. Herein, this review systematically summarizes recent progress in molecular mechanisms governing lactate metabolic reprogramming as well as its multiple biological functions in the central nervous system. Under physiological conditions, lactate regulates energy distribution via the astrocyte-neuron lactate shuttle, while mediates neural communication through receptors including G Protein-Coupled Receptor 81 and N-Methyl-d-Aspartate Receptor, thereby modulating synaptic plasticity and memory consolidation. In neurodegenerative pathologies (such as Alzheimer's and Parkinson's diseases), dysregulated lactate reprogramming is observed in the form of dynamic lactate imbalance, altered expression of monocarboxylate transporters and lactate dehydrogenase, and defective mitochondrial energy coupling. These perturbations further enhance neuronal damage by triggering neuroinflammation and perturbing epigenomic homeostasis (e.g., histone lactylation). Critical knowledge gaps remain unresolved: (1) The temporal dynamics of lactate flux during disease progression remain uncharacterized; (2) The spatial heterogeneity of lactate distribution across brain nuclei and its regulatory mechanisms are debated; (3) Consensus is lacking regarding functional alterations of core lactate metabolic components; and (4) The precise signaling cascades through which lactate modulates neurodegeneration require elucidation. By integrating contemporary research on central nervous system lactate reprogramming, this work provides novel perspectives on neurodegenerative disease mechanisms and establishes a theoretical framework for developing targeted therapeutic strategies that modulate lactate metabolism.

乳酸是中枢神经系统（CNS）中重要的能量底物和信号分子，在维持神经生理稳态和通过代谢重编程驱动神经退行性疾病的发病机制中起关键作用。本文就乳酸代谢重编程的分子调控机制及其在中枢神经系统中的多种生物学功能的研究进展作一综述。生理条件下，乳酸通过星形胶质细胞-神经元乳酸穿梭调节能量分布，同时通过G蛋白偶联受体81和n-甲基-d-天冬氨酸受体等受体介导神经通讯，从而调节突触可塑性和记忆巩固。在神经退行性疾病（如阿尔茨海默病和帕金森病）中，乳酸重编程失调表现为动态乳酸失衡、单羧酸转运体和乳酸脱氢酶表达改变以及线粒体能量偶联缺陷。这些扰动通过触发神经炎症和扰乱表观基因组稳态（如组蛋白乳酸化）进一步增强神经元损伤。关键的知识差距仍未得到解决：(1)疾病进展期间乳酸通量的时间动态仍未表征；(2)探讨了乳酸盐在脑核分布的空间异质性及其调控机制；(3)核心乳酸代谢成分的功能改变缺乏共识；(4)乳酸调节神经退行性变的精确信号级联需要阐明。通过整合中枢神经系统乳酸重编程的当代研究，本工作为神经退行性疾病的机制提供了新的视角，并为制定调节乳酸代谢的靶向治疗策略建立了理论框架。

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引用次数: 0

Imipramine improves motor impairments in a rat model of Parkinson's disease induced by 6-hydroxydopamine; the role of oxidative stress and neurotrophic factors 丙咪嗪改善6-羟多巴胺诱导的帕金森病大鼠模型的运动损伤氧化应激与神经营养因子的作用。

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology

Pub Date : 2026-01-13 DOI: 10.1016/j.expneurol.2026.115646

Mahdi Hajibabaei , Bagher Jafarvand , Elmira Beirami , Neda Valian

Introduction

Parkinson's disease (PD) is a progressive neurological disorder characterized by the loss of dopaminergic neurons in the substantia nigra and is associated with neuroinflammation, apoptosis, oxidative stress, and motor impairment. Imipramine, a tricyclic antidepressant, has a wide range of biological effects such as anti-inflammatory, anti-apoptotic, and free radical scavenging activities. The present study was designed to investigate the neuroprotective effect of imipramine in a rat model of PD induced by 6-hydroxydopamine (6-OHDA).

Methods

Male Wistar rats were treated with daily intraperitoneal administration of imipramine (20 mg/kg, for 14 days) starting 72 h after 6-OHDA injection (20 μg/rat; 4 μl in the right medial forebrain bundle (MFB)). The motor performance was assessed using the rotarod, beam, pole, and apomorphine-induced rotation tests. The protein levels of neurotrophic factors (BDNF, GDNF, and NT3) and factors involved in oxidative stress (MDA, CAT, SOD, GST, and GSH) were measured in the striatum by ELISA technique. The neuronal survival was also evaluated by Nissl staining.

Results

Our results showed that 6-OHDA caused motor impairments and neuronal cell death. It also significantly reduced the protein levels of neurotrophic factors and induced an oxidative stress response in the striatum of rats. Whereas, imipramine treatment effectively reduced 6-OHDA-induced motor deficits and neuronal cell death. This improvement was accompanied by an increase in neurotrophic factors, especially GDNF, as well as a reduction in oxidative stress through increased SOD levels.

Conclusion

These findings provide direct evidence that imipramine treatment contributes to improve of neuronal cell death and motor deficits, perhaps by increasing the striatal levels of SOD and GDNF, which play a key role in the survival of dopaminergic neurons. Further studies are also needed to elucidate the precise underlying molecular mechanisms of neuroprotective effects of imipramine.

简介：帕金森病（PD）是一种进行性神经系统疾病，以黑质多巴胺能神经元的丧失为特征，与神经炎症、细胞凋亡、氧化应激和运动障碍有关。丙咪嗪是一种三环抗抑郁药，具有广泛的生物效应，如抗炎、抗凋亡和自由基清除活性。本研究旨在探讨丙咪嗪对6-羟多巴胺（6-OHDA）诱导的PD大鼠模型的神经保护作用。方法：雄性Wistar大鼠注射6-OHDA(20 μl /大鼠，右侧内侧前脑束4 μl) 72 h后，每天腹腔注射丙咪嗪（20 mg/kg，连续14 d）。通过旋转杆、梁、杆和阿吗啡诱导旋转试验评估运动性能。采用ELISA法测定纹状体中神经营养因子（BDNF、GDNF、NT3）和氧化应激相关因子（MDA、CAT、SOD、GST、GSH）的蛋白水平。采用尼氏染色法观察神经元存活情况。结果：6-羟多巴胺可引起运动障碍和神经元细胞死亡。它还显著降低了大鼠纹状体中神经营养因子的蛋白质水平，并诱导了氧化应激反应。然而，丙咪嗪治疗可有效减少6-羟多巴胺诱导的运动缺陷和神经元细胞死亡。这种改善伴随着神经营养因子的增加，特别是GDNF，以及通过增加SOD水平减少氧化应激。结论：这些发现为丙咪嗪治疗有助于改善神经元细胞死亡和运动缺陷提供了直接证据，可能是通过增加纹状体中SOD和GDNF的水平，这在多巴胺能神经元的存活中起关键作用。还需要进一步的研究来阐明丙咪嗪神经保护作用的确切潜在分子机制。

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引用次数: 0

CCR2 knockdown attenuates post-hemorrhagic hydrocephalus and improves glymphatic function after intraventricular hemorrhage CCR2敲低可减轻出血性脑积水，改善脑室内出血后的淋巴功能。

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology

Pub Date : 2026-01-13 DOI: 10.1016/j.expneurol.2026.115644

Huajiang Deng , Shuang Zhang , Haoxiang Wang , Xiaoyin Liu , Kunhong Zhong , Keru Huang , Yuanyou Li , Ziang Deng , Aiping Tong , Liangxue Zhou

Post-hemorrhagic hydrocephalus (PHH) is a severe complication of intraventricular hemorrhage (IVH), yet its underlying mechanisms remain unclear. The glymphatic system (GS), a key pathway involved in cerebrospinal fluid (CSF) circulation and metabolic waste clearance, has recently been implicated in the pathogenesis of PHH. In this study, we employed a mouse model of IVH (n = 6 per group, assessed from 6 h to 28 days post-IVH) to investigate the role of the CCL2/CCR2 signaling axis in GS dysfunction and PHH progression. Behavioral tests, CSF tracer imaging, immunofluorescence, and Western blot analyses were used to assess CSF dynamics, AQP4 polarization, and relevant protein levels. The results showed that IVH induced upregulation of CCL2/CCR2, endoplasmic reticulum stress, and NF-κB activation, accompanied by the loss of AQP4 polarization and impairment of GS function. Notably, CCR2 inhibition was significantly associated with restored AQP4 polarization, improved CSF clearance, reduced ventricular enlargement, and ameliorated neurological deficits. These findings suggest that the CCL2/CCR2 signaling pathway may contribute to GS dysfunction in PHH and provide a foundation for exploring its therapeutic potential.

出血性脑积水（PHH）是脑室内出血（IVH）的严重并发症，但其潜在机制尚不清楚。glymphatic system （GS）是参与脑脊液（CSF）循环和代谢废物清除的关键途径，最近被认为与PHH的发病机制有关。在这项研究中，我们采用IVH小鼠模型（每组n = 6，IVH后6 h至28 天评估）来研究CCL2/CCR2信号轴在GS功能障碍和PHH进展中的作用。行为测试、脑脊液示踪成像、免疫荧光和Western blot分析用于评估脑脊液动力学、AQP4极化和相关蛋白水平。结果表明，IVH诱导CCL2/CCR2上调、内质网应激、NF-κB活化，同时伴有AQP4极化缺失和GS功能损伤。值得注意的是，CCR2抑制与恢复AQP4极化、改善CSF清除率、减少心室增大和改善神经功能缺陷显著相关。这些发现提示CCL2/CCR2信号通路可能参与PHH中GS功能障碍，并为探索其治疗潜力提供了基础。

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引用次数: 0

Prolonged antibiotic treatment accelerates neurological recovery and reduces long-term neuroinflammatory gene expression after experimental TBI in mice 长期抗生素治疗可加速小鼠实验性脑外伤后神经系统恢复并降低长期神经炎症基因表达。

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology

Pub Date : 2026-01-13 DOI: 10.1016/j.expneurol.2026.115645

Katharina Ritter , Katharina Petri , Julian Denninger , Yi Zhang , Yong Wang , Michael K.E. Schäfer

Background

Neuroprotective effects of antibiotic medications are reported in the context of experimental traumatic brain injury (TBI), but the choice of substances and treatment intervals are inconsistent.

Methods

In this study, we tested whether continuous posttraumatic administration of a combined broad-spectrum antibiotic regimen of vancomycin, amoxicillin, and clavulanic acid affects neurological recovery, structural brain damage and neuroinflammation following experimental TBI by controlled cortical impact in 80 adult male C57BL/6 mice.

Results

Antibiotic treatment led to accelerated recovery from posttraumatic neuromotor impairment and exploratory behavioural disorders. Reduced astrocytic activation and neuronal loss in the ipsilesional thalamic region in the early (5 days post injury, dpi) and attenuated neuroinflammatory gene expression in the late (30 dpi) period were observed alongside a severe disruption of the intestinal microbial spectrum after five days of antibiotic treatment, while the structural brain damage remained unaffected.

Conclusion

We demonstrated accelerated neurological recovery and long-lasting effects of antibiotic treatment on the neuroinflammatory response after experimental TBI. Increased plasma levels of lipopolysaccharide-binding protein and short-chain fatty acids were evaluated, yet not identified as potential modulators. As the observed effects can not entirely be linked to the intestinal dysbiosis, direct modulation of secondary brain damage by the antibiotic substances should be considered as an alternate mechanism.

背景：在实验性创伤性脑损伤（TBI）的背景下，已有抗生素药物的神经保护作用的报道，但药物的选择和治疗间隔并不一致。方法：在这项研究中，我们测试了80只成年雄性C57BL/6小鼠创伤后持续使用万古霉素、阿莫西林和克拉维酸联合广谱抗生素方案是否会影响实验性TBI后的神经恢复、结构性脑损伤和神经炎症。结果：抗生素治疗可加速创伤后神经运动障碍和探索性行为障碍的恢复。在早期（损伤后5 天）观察到同伤丘脑区域星形细胞激活减少和神经元丢失，在晚期（30 dpi）观察到神经炎症基因表达减弱，同时在5天抗生素治疗后肠道微生物谱严重破坏，而结构性脑损伤未受影响。结论：我们证明了抗生素治疗对实验性TBI后神经炎症反应的加速恢复和持久效果。血浆中脂多糖结合蛋白和短链脂肪酸水平的升高被评估，但未被确定为潜在的调节剂。由于观察到的影响不能完全与肠道生态失调有关，抗生素物质直接调节继发性脑损伤应被视为一种替代机制。

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引用次数: 0

Spatiotemporal multi-omics profiling of secondary brain injury after intracerebral hemorrhage in an optimized autologous blood-induced mouse model with human tissue validation 优化的自体血诱导小鼠脑出血后继发性脑损伤的时空多组学分析。

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology

Pub Date : 2026-01-13 DOI: 10.1016/j.expneurol.2026.115650

Yang Du , Guangshuo Li , Yijun Lin , Zeqiang Ji , Yiwei Shi , Xiaojing Zhang , Na Zhou , Jia Zhang , Kaijiang Kang , Xingquan Zhao , Liheng Bian

Background

Secondary brain injury (SBI) following intracerebral hemorrhage (ICH) involves complex molecular events such as oxidative stress, inflammation, and immune cell infiltration. Understanding their spatiotemporal patterns is essential for identifying therapeutic targets and optimal intervention windows.

Methods

We optimized an autologous blood-induced ICH mouse model and performed neuroimaging, behavioral testing, histological evaluation, and transcriptomic and proteomic analyses across multiple time points (Days 1, 3, 5, 8, and 12). Time-resolved analyses focused on dynamic changes in SBI-related pathways, including oxidative stress, ferroptosis, leukocyte migration, neutrophil extracellular trap (NET) formation, and phagocytic–lysosomal activity, with spatial validation by immunofluorescence and histology. Model refinements reduced blood coagulation and leakage, improving procedural success and reproducibility. In addition, imaging and perihematomal tissue from a patient 66 h after ICH onset were examined for comparison.

Results

Principal component and clustering analyses revealed a time-dependent molecular trajectory, with rapid early transcriptional changes followed by delayed but sustained protein-level responses. Markers of oxidative stress and ferroptosis (HMOX1, FTH1), adhesion molecules (VCAM1, CD11b), and phagocytic activity (CD68, CTSD) displayed distinct temporal and spatial expression patterns. NET formation peaked between Days 3 and 5 and then gradually declined. Human ICH tissue demonstrated similar activation of oxidative, inflammatory, and phagocytic pathways.

Conclusions

This study delineates the spatiotemporal dynamics of key pathways and molecules involved in secondary brain injury after ICH, revealing stage-specific molecular features and potential therapeutic windows. The optimized autologous blood-induced ICH model exhibits good stability, reproducibility, and relevance to human pathology.

背景：脑出血（ICH）后继发性脑损伤（SBI）涉及复杂的分子事件，如氧化应激、炎症和免疫细胞浸润。了解它们的时空模式对于确定治疗靶点和最佳干预窗口是必不可少的。方法：我们优化了自体血源性脑出血小鼠模型，并在多个时间点（第1、3、5、8和12天）进行神经影像学、行为测试、组织学评估以及转录组学和蛋白质组学分析。时间分辨分析侧重于sbi相关通路的动态变化，包括氧化应激、铁死亡、白细胞迁移、中性粒细胞胞外陷阱（NET）形成和吞噬细胞溶酶体活性，并通过免疫荧光和组织学进行空间验证。模型的改进减少了血液凝固和泄漏，提高了手术的成功率和可重复性。此外，影像学和血肿周围组织从患者66 h脑出血发作后检查进行比较。结果：主成分和聚类分析揭示了一个时间依赖的分子轨迹，快速的早期转录变化随后是延迟但持续的蛋白质水平反应。氧化应激和铁凋亡标志物（HMOX1, FTH1），粘附分子（VCAM1, CD11b）和吞噬活性（CD68， CTSD）表现出不同的时空表达模式。NET的形成在第3天至第5天达到顶峰，然后逐渐下降。人脑出血组织表现出类似的氧化、炎症和吞噬途径的激活。结论：本研究揭示了脑出血后继发性脑损伤关键通路和分子的时空动态，揭示了阶段性分子特征和潜在的治疗窗口。优化后的自体血源性脑出血模型具有良好的稳定性、可重复性和与人类病理的相关性。

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引用次数: 0

Machine learning for discovery of clinical pain biomarkers following spinal cord injury 用机器学习发现脊髓损伤后的临床疼痛生物标志物

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology

Pub Date : 2026-01-13 DOI: 10.1016/j.expneurol.2026.115649

Roxana Florea , Ki-Soo Jeong , Carl Y. Saab

Chronic pain is highly prevalent in patients with spinal cord injury (SCI) and further degrades the quality of life in individuals already struggling with somatic, motor, and autonomic deficits. The management of SCI pain is challenging, mainly due to the lack of reliable, FDA-approved diagnostics, effective therapies, and incomplete understanding of the underlying mechanisms. These limitations have led to increased efforts dedicated to the identification of objective pain biomarkers. However, the FDA has yet to approve a physiologically relevant biomarker for the assessment of pain in populations with SCI. Given the multidimensional nature of pain, there is increasing recognition that composite biomarkers are needed. In this paper, we review several candidate pain signatures and discuss how the inclusion of multi-modal features such as self-reported questionnaires and behavioural measures should also be considered in the identification of comprehensive biomarkers of SCI pain. Since multi-modal, large-scale data presents a particular computational challenge, we further argue that AI and ML approaches enable novel combinatorial designs of SCI pain biomarkers. The advantages of AI and ML methods, which continue to evolve at a rapid pace, include computational efficiency, discovery of latent or embedded patterns in complex data architectures, personalized diagnostics, and minimization of potential bias. We also caution against over-reliance on physiological or neural imaging features that ignore the demographic, motivational, emotional, cognitive and cultural dimensions of pain, while advocating for AI/ML models with improved interpretability.

慢性疼痛在脊髓损伤（SCI）患者中非常普遍，并且进一步降低了已经与躯体、运动和自主神经缺陷作斗争的个体的生活质量。脊髓损伤疼痛的管理是具有挑战性的，主要是由于缺乏可靠的，fda批准的诊断，有效的治疗方法，以及对其潜在机制的不完全了解。这些限制导致越来越多的努力致力于识别客观疼痛生物标志物。然而，FDA尚未批准用于评估脊髓损伤人群疼痛的生理相关生物标志物。鉴于疼痛的多维性，人们越来越认识到需要复合生物标志物。在本文中，我们回顾了几种候选的疼痛特征，并讨论了在识别脊髓损伤的综合生物标志物时应如何考虑多模态特征，如自我报告的问卷和行为测量。由于多模态、大规模数据提出了特殊的计算挑战，我们进一步认为人工智能和机器学习方法可以实现SCI疼痛生物标志物的新型组合设计。人工智能和机器学习方法的优势继续以快速的速度发展，包括计算效率、发现复杂数据架构中的潜在或嵌入模式、个性化诊断和最小化潜在偏差。我们还警告不要过度依赖生理或神经成像特征，这些特征忽略了疼痛的人口统计学、动机、情感、认知和文化维度，同时提倡具有更好可解释性的AI/ML模型。

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Letter to the Editor. Effect of encephalomyosynangiosis procedure on post stroke recovery in a permanent model of ischemic stroke. 给编辑的信。脑肌病合并术对永久性缺血性脑卒中模型脑卒中后恢复的影响。

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology

Pub Date : 2026-01-10 DOI: 10.1016/j.expneurol.2026.115641

Pian Gong, Yichun Zou

This correspondence comments on the methodological issues of Anthony et al. on encephalomyosynangiosis (EMS) for acute ischemic stroke in mice. The central issue is the clinically unrealistic intervention time of 4 h post-occlusion, which limits the translational relevance of the reported benefits in infarct reduction and recovery. Furthermore, the surgical design-specifically, the differential handling of the temporalis muscle between groups-introduces a potential confounder, as the excision in controls may alter baseline intracranial pressure compared to the preserved muscle in the EMS group. Details on sham procedures were also lacking. We suggest that employing a later, clinically pertinent time point and a more standardized surgical control would significantly strengthen the experimental model and the validity of its conclusions.

本文对Anthony等人关于小鼠急性缺血性中风脑肌病（EMS）的方法学问题进行了评论。中心问题是临床上不现实的4 h闭塞后干预时间，这限制了报道的梗死减少和恢复益处的转化相关性。此外，手术设计-特别是两组之间颞肌的不同处理-引入了潜在的混杂因素，因为与EMS组中保留的肌肉相比，对照组的切除可能会改变基线颅内压。虚假程序的细节也缺乏。我们建议采用更晚的临床相关时间点和更规范的手术控制将显著加强实验模型及其结论的有效性。

引用次数: 0