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重复性轻度闭合性颅脑损伤导致突触丢失及局部BOLD-fMRI信号同质性增加。

Repetitive Mild Closed-Head Injury Induced Synapse Loss and Increased Local BOLD-fMRI Signal Homogeneity.

作者信息

Markicevic Marija, Mandino Francesca, Toyonaga Takuya, Cai Zhengxin, Fesharaki-Zadeh Arman, Shen Xilin, Strittmatter Stephen M, Lake Evelyn M R

机构信息

Department of Radiology and Biomedical Imaging, School of Medicine, Yale University, New Haven, Connecticut, USA.

Department of Neurology, School of Medicine, Yale University, New Haven, Connecticut, USA.

出版信息

J Neurotrauma. 2024 Dec;41(23-24):2528-2544. doi: 10.1089/neu.2024.0095. Epub 2024 Sep 20.

Abstract

Repeated mild head injuries due to sports, or domestic violence and military service are increasingly linked to debilitating symptoms in the long term. Although symptoms may take decades to manifest, potentially treatable neurobiological alterations must begin shortly after injury. Better means to diagnose and treat traumatic brain injuries requires an improved understanding of the mechanisms underlying progression and means through which they can be measured. Here, we employ a repetitive mild traumatic brain injury (rmTBI) and chronic variable stress mouse model to investigate emergent structural and functional brain abnormalities. Brain imaging is achieved with [F]SynVesT-1 positron emission tomography, with the synaptic vesicle glycoprotein 2A ligand marking synapse density and BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI). Animals were scanned six weeks after concluding rmTBI/Stress procedures. Injured mice showed widespread in synaptic density coupled with an i in local BOLD-fMRI synchrony detected as regional homogeneity. Injury-affected regions with synapse density showed a in fMRI regional homogeneity. Taken together, these observations may reflect compensatory mechanisms following injury. Multimodal studies are needed to provide deeper insights into these observations.

摘要

因运动、家庭暴力或军事服役导致的反复轻度头部损伤与长期衰弱症状的关联日益增加。尽管症状可能需要数十年才会显现,但潜在可治疗的神经生物学改变必须在受伤后不久就开始。更好地诊断和治疗创伤性脑损伤需要更好地理解其进展的潜在机制以及测量这些机制的方法。在这里,我们采用重复性轻度创伤性脑损伤(rmTBI)和慢性可变应激小鼠模型来研究新出现的大脑结构和功能异常。通过[F]SynVesT-1正电子发射断层扫描进行脑成像,突触囊泡糖蛋白2A配体标记突触密度,并通过血氧水平依赖性功能磁共振成像(BOLD-fMRI)进行功能磁共振成像。在完成rmTBI/应激程序六周后对动物进行扫描。受伤小鼠的突触密度普遍降低,同时局部BOLD-fMRI同步性增加,表现为区域同质性增加。突触密度降低的损伤影响区域在功能磁共振成像区域同质性方面增加。综上所述,这些观察结果可能反映了损伤后的代偿机制。需要进行多模态研究以更深入地了解这些观察结果。

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