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脊髓损伤中针对小胶质细胞调节的靶向治疗与深度学习见解

Targeted therapy and deep learning insights into microglia modulation for spinal cord injury.

作者信息

Petillo Emilia, Veneruso Valeria, Gragnaniello Gianluca, Brochier Lorenzo, Frigerio Enrico, Perale Giuseppe, Rossi Filippo, Cardia Andrea, Orro Alessandro, Veglianese Pietro

机构信息

Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, Milano 20156, Italy.

Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, via Mancinelli 7, Milano 20131, Italy.

出版信息

Mater Today Bio. 2024 Jun 8;27:101117. doi: 10.1016/j.mtbio.2024.101117. eCollection 2024 Aug.

DOI:10.1016/j.mtbio.2024.101117
PMID:38975239
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11225820/
Abstract

Spinal cord injury (SCI) is a devastating condition that can cause significant motor and sensory impairment. Microglia, the central nervous system's immune sentinels, are known to be promising therapeutic targets in both SCI and neurodegenerative diseases. The most effective way to deliver medications and control microglial inflammation is through nanovectors; however, because of the variability in microglial morphology and the lack of standardized techniques, it is still difficult to precisely measure their activation in preclinical models. This problem is especially important in SCI, where the intricacy of the glia response following traumatic events necessitates the use of a sophisticated method to automatically discern between various microglial cell activation states that vary over time and space as the secondary injury progresses. We address this issue by proposing a deep learning-based technique for quantifying microglial activation following drug-loaded nanovector treatment in a preclinical SCI model. Our method uses a convolutional neural network to segment and classify microglia based on morphological characteristics. Our approach's accuracy and efficiency are demonstrated through evaluation on a collection of histology pictures from injured and intact spinal cords. This robust computational technique has potential for analyzing microglial activation across various neuropathologies and demonstrating the usefulness of nanovectors in modifying microglia in SCI and other neurological disorders. It has the ability to speed development in this crucial sector by providing a standardized and objective way to compare therapeutic options.

摘要

脊髓损伤(SCI)是一种破坏性疾病,可导致严重的运动和感觉障碍。小胶质细胞作为中枢神经系统的免疫哨兵,在脊髓损伤和神经退行性疾病中都是很有前景的治疗靶点。递送药物和控制小胶质细胞炎症的最有效方法是通过纳米载体;然而,由于小胶质细胞形态的变异性以及缺乏标准化技术,在临床前模型中精确测量它们的激活状态仍然很困难。这个问题在脊髓损伤中尤为重要,因为创伤事件后胶质细胞反应的复杂性需要使用一种复杂的方法来自动区分随着继发性损伤进展而在时间和空间上变化的各种小胶质细胞激活状态。我们通过提出一种基于深度学习的技术来解决这个问题,该技术用于在临床前脊髓损伤模型中量化载药纳米载体治疗后的小胶质细胞激活情况。我们的方法使用卷积神经网络根据形态特征对小胶质细胞进行分割和分类。通过对来自受伤和完整脊髓的组织学图片集进行评估,证明了我们方法的准确性和效率。这种强大的计算技术有潜力分析各种神经病理学中的小胶质细胞激活情况,并证明纳米载体在脊髓损伤和其他神经系统疾病中修饰小胶质细胞的有效性。它有能力通过提供一种标准化和客观的方式来比较治疗方案,从而加速这一关键领域的发展。

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Adv Mater. 2024 Jan;36(3):e2307747. doi: 10.1002/adma.202307747. Epub 2023 Dec 2.
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Microglial morphometric analysis: so many options, so little consistency.小胶质细胞形态计量分析:选择众多,一致性却很差。
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Microglia morphotyping in the adult mouse CNS using hierarchical clustering on principal components reveals regional heterogeneity but no sexual dimorphism.
利用主成分层次聚类分析在成年小鼠中枢神经系统中对小胶质细胞形态进行分型,揭示了区域性异质性,但不存在性别二态性。
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Microglia morphophysiological diversity and its implications for the CNS.小胶质细胞形态生理学多样性及其对中枢神经系统的影响。
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A novel automated morphological analysis of Iba1+ microglia using a deep learning assisted model.一种使用深度学习辅助模型对Iba1+小胶质细胞进行的新型自动形态学分析。
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