Brain Research最新文献_第4页

Retraction notice to "Sulforaphane protects brains against hypoxic-ischemic injury through induction of Nrf2-dependent phase 2 enzyme" [Brain Res. 1343 (2010) 178-185]. “萝卜硫素通过诱导nrf2依赖的2期酶来保护大脑免受缺氧缺血性损伤”的撤回通知[脑科学进展]. 1343(2010)178-185。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-03-13 DOI: 10.1016/j.brainres.2026.150255

Zhang Ping, Wenwu Liu, Zhimin Kang, Jianmei Cai, Qiusha Wang, Ni Cheng, Sujian Wang, Shizhong Wang, John H Zhang, Xuejun Sun

引用次数: 0

Ding-zhi-xiao-wan attenuates Alzheimer's disease pathology and cognitive deficits in mouse model. 定智消丸减轻阿尔茨海默病小鼠模型的病理和认知缺陷。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-03-11 DOI: 10.1016/j.brainres.2026.150263

Zhulei Miao, Zhiling Yang, Qilin Huang, Jianhua Fan, Jinxia Sun, Lixin Wang, Yuejuan Zheng, Guizhen Yang

Background: Ding-zhi-xiao-wan (DZXW) is a classic prescription applied for the therapy of forgetfulness and dizziness. However, the mechanisms of DZXW in ameliorating cognition deficits in Alzheimer's disease (AD) have not been fully determined. To comprehensively illuminate the overall beneficial effects and the underlying molecular mechanisms of DZXW to AD.

Methods: An initial network pharmacology analysis was performed, including of construction of multiple networks and enrichment of gene ontology, and analysis of signal pathway. Furthermore, animal experiments were performed to validate the predicted molecular mechanisms from network pharmacology.

Results: 39 active compounds in DZXW corresponding to 224 genes related to AD protection were found. The therapeutic mechanisms of DZXW to protect AD predicted from the network pharmacology were primarily related to the negative regulation of neuroinflammation and oxidative stress. Compared to AD model mice, DZXW-administeredmice explored new objects more often, demonstrated a significantly shorter escape latency, passed through the platform more frequently, and stayed in the platform quadrant longer. Furthermore, DZXW-administeredmice showed a markedly less burden of Aβ plaques, lower number of activated microglias in the mice brain, enhanced activity of superoxide dismutase (SOD) and glutathione (GSH), and lower level of malondialdehyde (MDA) in mice.

Conclusions: DZXW could be a therapeutic candidate for AD by inhibiting neuroinflammation and oxidative stress.

背景：定智消丸是治疗健忘头晕的经典方药。然而，DZXW改善阿尔茨海默病（AD）认知缺陷的机制尚未完全确定。全面阐明DZXW对AD的整体有益作用及其潜在的分子机制。方法：进行初步网络药理学分析，包括构建多网络、丰富基因本体、分析信号通路等。此外，通过动物实验验证了网络药理学预测的分子机制。结果：DZXW中发现了39个活性化合物，对应224个AD保护相关基因。网络药理学预测DZXW对AD的治疗机制主要与神经炎症和氧化应激的负调控有关。与AD模型小鼠相比，dzxw给药小鼠探索新物体的频率更高，逃避潜伏期明显缩短，通过平台的频率更高，在平台象限停留的时间更长。此外，dzxw给药小鼠的a β斑块负担明显减轻，小鼠脑内激活的小胶质细胞数量减少，超氧化物歧化酶（SOD）和谷胱甘肽（GSH）活性增强，丙二醛（MDA）水平降低。结论：DZXW可能通过抑制神经炎症和氧化应激成为治疗AD的候选药物。

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引用次数: 0

Sex- and age- dependent modulation of synaptic proteins and behavioral variability in a postnatal valproic acid model. 出生后丙戊酸模型中突触蛋白和行为变异的性别和年龄依赖性调节。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-03-10 DOI: 10.1016/j.brainres.2026.150261

Emre Tughan, Halime Dana, Ozge Nur Yilmaz, Fatma Kocum, Cicek Demiruz, Esra Demirci, Elif Funda Sener

Valproic acid (VPA) exposure is widely used to model autism spectrum disorder (ASD)-like phenotypes; however, the developmental timing and sex-specific molecular consequences of postnatal exposure remain incompletely understood. Disruptions in synaptogenesis and synaptic protein dynamics are considered central to the neurobiological underpinnings of ASD. This study investigated age- and sex-dependent behavioral and synaptic alterations following postnatal VPA administration during a critical developmental window (P30-P60). C57BL/6 female and male mice were exposed to a single intraperitoneal dose of VPA on postnatal day 14. Behavioral assessments included social interaction, open field, olfactory preference, and Morris water maze tests. Molecular analyses focused on the postsynaptic proteins Neurogranin (Nrgn) and PSD-95 (Dlg4) across the hippocampus, prefrontal cortex, and olfactory bulb. Postnatal VPA exposure produced age- and sex-dependent behavioral variability rather than uniform deficits. Males exhibited more pronounced modulation in locomotor and social parameters, whereas females showed relative resilience in spatial learning measures. In the hippocampus, VPA induced a significant increase in Nrgn mRNA and PSD-95 protein in 1-month-old males, suggesting temporally restricted synaptic remodeling during early maturation. These molecular alterations were region-specific and interaction-driven, with limited treatment effects observed in the prefrontal cortex and olfactory bulb. Importantly, protein levels were primarily influenced by age and sex rather than treatment alone, indicating tightly regulated developmental modulation rather than sustained synaptic loss. Collectively, these findings demonstrate that postnatal VPA exposure perturbs the temporal dynamics of synaptic maturation in a sex- and region-dependent manner, highlighting hippocampal vulnerability during adolescence. The results emphasize the importance of incorporating developmental stage and biological sex in mechanistic studies of ASD-related neuroplasticity.

丙戊酸（VPA）暴露被广泛用于模拟自闭症谱系障碍（ASD）样表型；然而，出生后暴露的发育时间和性别特异性分子后果仍不完全清楚。突触发生和突触蛋白动力学的中断被认为是ASD的神经生物学基础的核心。本研究调查了出生后在关键发育窗口期（P30-P60）服用VPA后的年龄和性别依赖性行为和突触改变。C57BL/6雌性和雄性小鼠于出生后第14天单次腹腔注射VPA。行为评估包括社会互动、野外、嗅觉偏好和Morris水迷宫测试。分子分析主要集中在海马、前额叶皮层和嗅球的突触后蛋白神经粒蛋白（Nrgn）和PSD-95 （Dlg4）。出生后VPA暴露产生了年龄和性别依赖的行为变异，而不是统一的缺陷。男性在运动和社会参数方面表现出更明显的调节，而女性在空间学习方面表现出相对的弹性。在海马体中，VPA诱导1月龄雄性海马Nrgn mRNA和PSD-95蛋白显著增加，提示早熟期突触重构受到暂时性限制。这些分子改变是区域特异性和相互作用驱动的，在前额叶皮层和嗅球中观察到的治疗效果有限。重要的是，蛋白质水平主要受年龄和性别的影响，而不是单独的治疗，这表明严格调节的发育调节，而不是持续的突触丧失。总的来说，这些发现表明，出生后的VPA暴露以性别和区域依赖的方式扰乱了突触成熟的时间动态，突出了青春期海马的脆弱性。这些结果强调了将发育阶段和生理性别纳入asd相关神经可塑性机制研究的重要性。

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引用次数: 0

Retraction notice to "Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress" [Brain Res. 1328 (2010) 152-161]. “富氢盐水通过减少氧化应激改善淀粉样β诱导的阿尔茨海默病大鼠模型的记忆功能”[脑科学进展，2010,28(1):152-161]。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-03-06 DOI: 10.1016/j.brainres.2026.150251

Jian Li, Cai Wang, John H Zhang, Jian-Mei Cai, Yun-Peng Cao, Xue-Jun Sun

引用次数: 0

Retraction notice to "Granulocyte-colony stimulating factor inhibits apoptotic neuron loss after neonatal hypoxia-ischemia in rats" [Brain Res. 1145 (2007) 227-238]. “粒细胞集落刺激因子对大鼠新生儿缺氧缺血后凋亡神经元损失的抑制作用”[脑科学杂志]. 1145(2007)227-238]。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-03-05 DOI: 10.1016/j.brainres.2026.150250

Kenichiro Yata, Gerald A Matchett, Tamiji Tsubokawa, Jiping Tang, Kenji Kanamaru, John H Zhang

引用次数: 0

A mouse model of a patient derived P544L mutation in the Slc6a8 gene shows hypoactivity and cognitive deficits 患者衍生的Slc6a8基因P544L突变的小鼠模型显示出多动症和认知缺陷。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-03-01 Epub Date: 2026-01-05 DOI: 10.1016/j.brainres.2026.150151

Marla K. Perna , Lara N. Gechijian , Heather S. Blanchette , Rosalyn Liou , Michael T. Williams , Charles V. Vorhees , Matthew R. Skelton

Creatine (CR) is essential for normal brain function. A lack of brain CR results in intellectual disability, epilepsy, and language delay in humans. The most common cause of CR deficiency in humans results from mutations in the CR transporter (SLC6A8). Several large deletion models of Slc6a8 have been characterized and are excellent models for global creatine loss. However, other SLC6A8 variants are reported in humans with creatine transporter deficiency (CTD), including missense mutations, deletions, and point mutations resulting in phenotypes ranging from mild to severe in humans. The purpose of these experiments was to determine if mice carrying a point mutation of the Slc6a8 gene showed cognitive deficits, further validating a new model of CTD. These Slc6a8 knock-in (Slc6a8^P544L) mice carry the P544L proline to leucine substitution seen in some humans with CTD. The Slc6a8^P544L mice have lower overall body weight and lower brain creatine content. Behavioral assessment revealed deficits in spatial memory but not associative or object recognition memory in Slc6a8^P544L mice. These findings are in line with clinical findings and other CTD models. In addition, we show that Slc6a8^P544L mice are hypoactive in a home-cage environment. These experiments support the use of Slc6a8^P544L mice as a valid representative of behavioral changes in human patients and to develop targeted therapies to rescue specific behavioral deficits in CTD.

肌酸（CR）是正常脑功能所必需的。大脑CR的缺乏会导致人类的智力残疾、癫痫和语言迟缓。人类CR缺乏的最常见原因是CR转运体（SLC6A8）的突变。Slc6a8的几个大缺失模型已经被表征，并且是全球肌酸损失的优秀模型。然而，其他SLC6A8变异在肌酸转运蛋白缺乏症（CTD）患者中也有报道，包括错义突变、缺失和点突变，导致人类的表型从轻微到严重不等。这些实验的目的是确定携带Slc6a8基因点突变的小鼠是否存在认知缺陷，进一步验证一种新的CTD模型。这些Slc6a8敲入（Slc6a8P544L）小鼠携带P544L脯氨酸到亮氨酸的替代，在一些患有CTD的人身上看到。Slc6a8P544L小鼠总体体重较低，脑肌酸含量较低。行为评估显示Slc6a8P544L小鼠存在空间记忆缺陷，但不存在联想记忆和物体识别记忆缺陷。这些发现与临床结果和其他CTD模型一致。此外，我们发现Slc6a8P544L小鼠在家庭笼环境中活性降低。这些实验支持使用Slc6a8P544L小鼠作为人类患者行为变化的有效代表，并开发靶向治疗来挽救CTD中的特定行为缺陷。

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引用次数: 0

Elevated FKBP5 expression associates with epilepsy-related molecular changes and promotes neuronal hyperexcitability FKBP5表达升高与癫痫相关的分子变化有关，并促进神经元的高兴奋性。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-03-01 Epub Date: 2026-01-08 DOI: 10.1016/j.brainres.2026.150157

Meng Cai , Shuyang Wang , Mingsu Liu , Bin Lai , Chen Chen , Jing Ding , Xin Wang

Objective

Epilepsy is one of the neurological disorders, characterized by recurrent, spontaneous seizures arising from neuronal hyperexcitability and hypersynchrony in the brain. The mechanisms of epilepsy are intricate and remain elusive. FKBP5 has emerged as a significant protein implicated in neurological disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This study aims to investigate the role of FKBP5 in a kainic acid (KA)-induced intrahippocampal epilepsy model and assessed how FKBP5 gain-of-function and FKBP51 inhibition influence neurotransmitter dynamics and neuronal excitability.

Methods

We examined the expression of FKBP5 in the hippocampus of the kainic acid (KA)-induced epilepsy model. To explore the impact of FKBP5 on neuronal activity, we overexpressed FKBP5 in primary cortical neurons and astrocytes, assessing extracellular glutamate levels in neuron–astrocytes co-cultures with or without the FKBP51-selective inhibitor SAFit2 (250 nM). Intrinsic excitability, voltage-gated Na⁺ currents, and network activity were evaluated using whole-cell patch-clamp recordings and high-density microelectrode arrays (HD-MEAs).

Results

We observed an elevated level of FKBP5 in the hippocampus of a kainic acid (KA)-induced chronic epilepsy mouse model, whereas cortical FKBP5 did not show clear changes across the examined post-insult time points.. Moreover, FKBP5 overexpression induced a remarkable increase in the extracellular glutamate level in co-cultured primary cortical neurons and astrocytes. Intriguingly, FKBP5 overexpression modifies the electrophysiological properties of primary neurons, resulting in increased intrinsic excitability and enhanced Na⁺ currents. Additionally, the network activity exhibits hyperexcitability with FKBP5 overexpression. Notably, SAFit2 treatment was also associated with elevated extracellular glutamate in the co-culture system, while intracellular FKBP5 and EAAT2 protein levels showed no significant group differences in the current dataset.

Conclusion

These findings suggested that FKBP5 played a significant role in regulating neuronal excitability and extracellular glutamate homeostasis. However, due to discrete sampling and the lack of continuous seizure monitoring, the present in vivo data do not establish a definitive causal contribution of FKBP5 to epileptogenesis, warranting future studies integrating longitudinal EEG and cell-type-specific manipulations.

目的：癫痫是一种神经系统疾病，其特征是由大脑神经元的高兴奋性和高同步性引起的反复、自发发作。癫痫的机制是复杂的，仍然难以捉摸。FKBP5是一种与阿尔茨海默病（AD）和帕金森病（PD）等神经系统疾病有关的重要蛋白。本研究旨在探讨FKBP5在kainic acid （KA）诱导的海马内癫痫模型中的作用，并评估FKBP5的功能获得和FKBP51的抑制如何影响神经递质动力学和神经元兴奋性。方法：检测kainic acid （KA）诱导癫痫模型海马中FKBP5的表达。为了探索FKBP5对神经元活性的影响，我们在原代皮质神经元和星形胶质细胞中过表达FKBP5，评估在有或没有fkbp51选择性抑制剂SAFit2（250 nM）的情况下，神经元-星形胶质细胞共培养的细胞外谷氨酸水平。使用全细胞膜片钳记录和高密度微电极阵列（hd - mea）来评估固有兴奋性、电压门控Na+电流和网络活性。结果：我们观察到kainic酸（KA）诱导的慢性癫痫小鼠模型海马中FKBP5水平升高，而皮质FKBP5在检查后损伤时间点没有显示出明显的变化。此外，FKBP5过表达诱导共培养皮层神经元和星形胶质细胞的胞外谷氨酸水平显著升高。有趣的是，FKBP5过表达改变了初级神经元的电生理特性，导致内在兴奋性增加和Na+电流增强。此外，FKBP5过表达时，网络活动表现出高兴奋性。值得注意的是，在共培养系统中，SAFit2处理也与细胞外谷氨酸升高有关，而细胞内FKBP5和EAAT2蛋白水平在当前数据集中没有显着的组差异。结论：FKBP5在调节神经元兴奋性和细胞外谷氨酸稳态中发挥重要作用。然而，由于离散采样和缺乏连续的癫痫监测，目前的体内数据并不能确定FKBP5与癫痫发生的明确因果关系，因此未来的研究需要结合纵向脑电图和细胞类型特异性操作。

{"title":"Elevated FKBP5 expression associates with epilepsy-related molecular changes and promotes neuronal hyperexcitability","authors":"Meng Cai , Shuyang Wang , Mingsu Liu , Bin Lai , Chen Chen , Jing Ding , Xin Wang","doi":"10.1016/j.brainres.2026.150157","DOIUrl":"10.1016/j.brainres.2026.150157","url":null,"abstract":"<div><h3>Objective</h3><div>Epilepsy is one of the neurological disorders, characterized by recurrent, spontaneous seizures arising from neuronal hyperexcitability and hypersynchrony in the brain. The mechanisms of epilepsy are intricate and remain elusive. FKBP5 has emerged as a significant protein implicated in neurological disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This study aims to investigate the role of FKBP5 in a kainic acid (KA)-induced intrahippocampal epilepsy model and assessed how FKBP5 gain-of-function and FKBP51 inhibition influence neurotransmitter dynamics and neuronal excitability.</div></div><div><h3>Methods</h3><div>We examined the expression of FKBP5 in the hippocampus of the kainic acid (KA)-induced epilepsy model. To explore the impact of FKBP5 on neuronal activity, we overexpressed FKBP5 in primary cortical neurons and astrocytes, assessing extracellular glutamate levels in neuron–astrocytes co-cultures with or without the FKBP51-selective inhibitor SAFit2 (250 nM). Intrinsic excitability, voltage-gated Na<sup>+</sup> currents, and network activity were evaluated using whole-cell patch-clamp recordings and high-density microelectrode arrays (HD-MEAs).</div></div><div><h3>Results</h3><div>We observed an elevated level of FKBP5 in the hippocampus of a kainic acid (KA)-induced chronic epilepsy mouse model, whereas cortical FKBP5 did not show clear changes across the examined post-insult time points.. Moreover, FKBP5 overexpression induced a remarkable increase in the extracellular glutamate level in co-cultured primary cortical neurons and astrocytes. Intriguingly, FKBP5 overexpression modifies the electrophysiological properties of primary neurons, resulting in increased intrinsic excitability and enhanced Na<sup>+</sup> currents. Additionally, the network activity exhibits hyperexcitability with FKBP5 overexpression. Notably, SAFit2 treatment was also associated with elevated extracellular glutamate in the co-culture system, while intracellular FKBP5 and EAAT2 protein levels showed no significant group differences in the current dataset.</div></div><div><h3>Conclusion</h3><div>These findings suggested that FKBP5 played a significant role in regulating neuronal excitability and extracellular glutamate homeostasis. However, due to discrete sampling and the lack of continuous seizure monitoring, the present <em>in vivo</em> data do not establish a definitive causal contribution of FKBP5 to epileptogenesis, warranting future studies integrating longitudinal EEG and cell-type-specific manipulations.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1874 ","pages":"Article 150157"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lysergic acid diethylamide modulates hippocampal and cortical local field potential oscillatory rhythms in male mice 麦角酸二乙胺调节雄性小鼠海马和皮质局部场电位振荡节律

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-03-01 Epub Date: 2026-01-02 DOI: 10.1016/j.brainres.2025.150142

B.S. Rabinovitch , N. Silverman , D. Ji , D. Shizgal , E.C. Lewis , P.L. Carlen

Background and rationale

Lysergic acid diethylamide (LSD) is a promising therapeutic for psychiatric disorders, but its physiological profile on the nervous system remains elusive. Rodent electrophysiological data has utilized in vivo single-unit electrophysiology recordings, while clinical neurophysiology studies have focused on spectral signatures using electroencephalography (EEG) and magnetoencephalography (MEG). No study to date has examined these spectral signatures in freely-behaving mice. Studying neural activity when an animal is physically restricted (i.e. head-fixed recordings) is stressful to animals, which informed our decision to avoid this confound of additional physical stress on observed effects. Moreover, how LSD acutely modulates intracranial oscillatory rhythms is not known.

Experimental approach

Here we present the first in vivo electrophysiological investigation of LSD’s cortico-hippocampal effects in freely-behaving male C57BL/6J mice using intracranial EEG (iEEG) recordings. We did not posit a hypothesis concerning the specific effects of LSD on power spectral density (PSD) due to the lack of preclinical literature as well as LSD’s promiscuous pharmacological profile. This study was purely exploratory.

Key results

Following intraperitoneal (IP) administration of 30 µg/kg LSD, there was a global decrease in PSD signal power in both broadband and discrete narrow band oscillatory rhythms of the ventral hippocampus CA1 and CA3 regions. Similar but less robust effects were observed in the somatosensory and medial prefrontal cortices. These data confer with the existing clinical neurophysiology data. Lastly, LSD increased between-subject PSD signal power variance, suggesting individual-specific effects.

Conclusion and implications

Our data lends further credibility to the entropic brain theory of psychedelic drug actions. We conclude that the preclinical intracranial acute spectral signatures of LSD coincide with their clinical counterparts. Further work is needed to study cross-regional connectivity, such as frequency coupling.

背景与理由麦角酸二乙胺（LSD）是一种很有前景的治疗精神疾病的药物，但其对神经系统的生理作用尚不清楚。啮齿动物电生理数据利用体内单单元电生理记录，而临床神经生理学研究则集中在使用脑电图（EEG）和脑磁图（MEG）的频谱特征上。到目前为止，还没有研究在自由行为的老鼠身上检测这些光谱特征。当动物受到身体限制（即头部固定录音）时，研究神经活动对动物来说是有压力的，这告诉我们决定避免这种额外的身体压力对观察效果的混淆。此外，LSD如何剧烈调节颅内振荡节律尚不清楚。实验方法在此，我们首次使用脑电（iEEG）记录在自由行为的雄性C57BL/6J小鼠中进行了LSD皮质-海马效应的体内电生理研究。由于缺乏临床前文献以及LSD混杂的药理学特征，我们没有提出关于LSD对功率谱密度（PSD）的具体影响的假设。这项研究纯粹是探索性的。主要结果：腹腔注射30µg/kg LSD后，海马腹侧CA1和CA3区宽带和离散窄带振荡节律的PSD信号功率均下降。在体感觉和内侧前额叶皮层中观察到类似但不那么强大的效应。这些数据与现有的临床神经生理学数据一致。最后，LSD增加了受试者之间的PSD信号功率差异，表明个体特异性效应。结论和意义我们的数据进一步证实了迷幻药物作用的熵脑理论。我们得出结论，LSD的临床前颅内急性谱特征与临床相吻合。需要进一步研究跨区域的连通性，如频率耦合。

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引用次数: 0

Plasma protein signatures associated with functional outcome heterogeneity in rtPA-treated acute ischemic stroke 血浆蛋白特征与rtpa治疗的急性缺血性卒中功能结局异质性相关。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-03-01 Epub Date: 2025-12-31 DOI: 10.1016/j.brainres.2025.150121

Lanjing Wang , Tong Shen , Shuangfeng Huang , Yue Hu , Yumin Luo , Sijie Li

Objectives

The mechanisms underlying heterogeneous neurological functional outcomes following recombinant tissue plasminogen activator (rtPA) therapy in acute ischemic stroke (AIS) remain elusive. This exploratory study aimed to explore proteomic signatures associated with rtPA response using data-independent acquisition (DIA) mass spectrometry.

Methods

We performed plasma proteomic profiling on 10 AIS patients (6 with favorable outcomes [90-day mRS ≤ 2], 4 with unfavorable outcomes [90-day mRS > 2]) and 6 healthy controls. Differential protein expression analysis, functional enrichment (GO, KEGG), and weighted gene co-expression network analysis (WGCNA) were applied to identify outcome-related proteins and pathways.

Results

AIS induced significant perturbations in energy metabolism, inflammatory responses, and oxidative stress responses, with more pronounced proteomic dysregulation observed in unfavorable-outcome patients. The differentially expressed proteins (DEPs) associated with rtPA therapy (such as CP, CA1, CA2, ABCC2, COL1A2) were functionally linked to oxidative stress, metabolic transport, and transforming growth factor (TGF)-β receptor signaling. Pathway analysis revealed enrichment in porphyrin metabolism, nitrogen metabolism, and ABC transporter pathways. Additionally, DEPs between patients with distinct outcomes demonstrated significant enrichment in NF-κB signaling pathway and ABC transporters.

Conclusions

This exploratory study suggests that rtPA may influence acid-base balance, redox homeostasis, and TGF-β signaling. The association of NF-κB signaling and ABC transporters with outcome heterogeneity highlights their potential for further investigation as therapeutic targets. These findings provide preliminary mechanistic insights that warrant validation in larger cohorts.

目的：重组组织型纤溶酶原激活剂（rtPA）治疗急性缺血性卒中（AIS）后异质性神经功能预后的机制尚不明确。本探索性研究旨在利用数据独立获取（DIA）质谱法探索与rtPA反应相关的蛋白质组学特征。方法：我们对10例AIS患者（6例预后良好[90天mRS ≤ 2]，4例预后不良[90天mRS ≤ 2]）和6名健康对照进行了血浆蛋白质组学分析。应用差异蛋白表达分析、功能富集（GO， KEGG）和加权基因共表达网络分析（WGCNA）来鉴定结果相关蛋白和途径。结果：AIS诱导了能量代谢、炎症反应和氧化应激反应的显著扰动，在预后不良的患者中观察到更明显的蛋白质组失调。与rtPA治疗相关的差异表达蛋白（DEPs）（如CP、CA1、CA2、ABCC2、COL1A2）在功能上与氧化应激、代谢转运和转化生长因子(TGF)-β受体信号传导相关。通路分析显示卟啉代谢、氮代谢和ABC转运蛋白通路富集。此外，不同结局患者之间的dep显示NF-κB信号通路和ABC转运蛋白显著富集。结论：本探索性研究提示rtPA可能影响酸碱平衡、氧化还原稳态和TGF-β信号传导。NF-κB信号传导和ABC转运蛋白与结果异质性的关联突出了它们作为治疗靶点的进一步研究潜力。这些发现提供了初步的机制见解，值得在更大的队列中验证。

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引用次数: 0

Aperiodic slope reflects glutamatergic tone in the human brain 非周期斜率反映人脑的谷氨酸能张力。

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.brainres.2026.150161

Aislin A. Sheldon , Hannah R. Moser , Kamar S. Abdullahi , Karly D. Allison , Carter B. Mulder , Samantha A. Montoya , Scott R. Sponheim , Małgorzata Marjańska , Michael-Paul Schallmo

Excitatory and inhibitory neural processes are essential for every aspect of brain function, but current non-invasive neuroimaging methods to study these in the human brain are limited. Recent studies which separate oscillatory and aperiodic components of electrophysiological power spectra have highlighted a relationship between aperiodic activity and functional brain states. Studies in both animal models and humans suggest that the aperiodic slope of electrophysiological power spectra reflects the local balance of excitatory:inhibitory (E:I) synaptic transmission. Aperiodic slope varies across individuals, brain states, and clinical populations, which may reflect important differences in E:I balance. However, there is currently a lack of evidence linking aperiodic slope to other measures of excitation and inhibition in the human brain. Here, we show that flatter (less steep) aperiodic slopes from human electroencephalography (EEG) are associated with higher concentrations of the excitatory neural metabolite glutamate measured with 7 T magnetic resonance spectroscopy (MRS) in the occipital lobe at rest. This suggests that individual differences in aperiodic neural activity reflect cortical glutamate concentrations, providing important insight for understanding changes in neural excitation across brain states and neuropsychiatric populations (e.g., schizophrenia) where glutamatergic function may differ. Our results support the use of aperiodic slope as a non-invasive marker for excitatory tone in the human brain.

兴奋性和抑制性神经过程对于脑功能的各个方面都是必不可少的，但目前在人脑中研究这些过程的非侵入性神经成像方法是有限的。最近的研究分离了电生理功率谱的振荡和非周期成分，强调了非周期活动与脑功能状态之间的关系。动物模型和人体研究表明，电生理功率谱的非周期斜率反映了兴奋性：抑制性（E:I）突触传递的局部平衡。非周期斜率因个体、大脑状态和临床人群而异，这可能反映了E:I平衡的重要差异。然而，目前缺乏将非周期斜率与人脑中其他兴奋和抑制措施联系起来的证据。在这里，我们发现，人类脑电图（EEG）显示的更平坦（不太陡峭）的非周期斜坡与静止时枕叶中7 T磁共振波谱（MRS）测量的兴奋性神经递质谷氨酸浓度较高有关。这表明非周期性神经活动的个体差异反映了皮质谷氨酸浓度，为理解谷氨酸能功能可能不同的大脑状态和神经精神人群（如精神分裂症）的神经兴奋变化提供了重要见解。我们的研究结果支持使用非周期斜率作为人类大脑兴奋性张力的非侵入性标记。

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引用次数: 0