Alterations in Endogenous Stem Cell Populations in the Acute Phase of Blast-Induced Spinal Cord Injury.

IF 2.5 4区 医学 Q3 NEUROSCIENCES
David Valenti, Carly Norris, Margaret Yuan, Benita Luke, Rachel Thomas, Josiah Thomas, Susan Murphy, Pamela VandeVord, Kelly C S Roballo
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引用次数: 0

Abstract

Background: Blast-induced spinal cord injury (bSCI) is prevalent among military populations and frequently leads to irreversible spinal cord tissue damage that manifests as sensorimotor and autonomic nervous system dysfunction. Clinical recovery from bSCI has been proven to be multifactorial, as it is heavily dependent on the function of numerous cell populations in the tissue environment, as well as extensive ongoing inflammatory processes. This varied recovery process is thought to be due to irreversible spinal cord damage after 72 hours post-injury. Stem cell therapy for spinal cord injuries has long been investigated due to these cells' proliferative nature, ability to enhance neuro-regeneration, neuroprotection, remyelination of axons, and modulation of the immune and inflammatory responses. Therefore, this study hypothesizes that the impaired function after injury is due to a lack of specific ectoderm and neural stem cell population activity at the injury site.

Methods: This study aimed to elucidate changes in endogenous stem cell patterns by evaluating immunohistochemical staining densities of various stem cell markers using a preclinical thoracolumbar bSCI model. Analysis was performed 24-, 48-, and 72 hours following blast exposure. Behavior tests to assess sensory and mechanical functions were also performed.

Results: The following Cluster of differentiation (CD) markers CD105, CD45, CD133, and Vimentin, Nanog homebox (NANOG), and sex determining region Y HMG-box 2 (SOX2) positive cell populations were significantly elevated with trending increases in Octamer-binding transcription factor 4 (OCT4) in the thoracolumbar region of spinal cord tissue at 72 hours following bSCI (p < 0.05). Behavior analyses showed significant decreases in paw withdrawal thresholds in the hind limbs and changes in locomotion at 48- and 72 hours post-injury (p < 0.05).

Conclusions: The significant increase in mesenchymal, pluripotent, and neural stem cell populations within the thoracolumbar region post-injury suggests that migratory patterns of stem cell populations are likely altered in response to bSCI. Behavioral deficits were consistent with those experienced by military personnel, such as increased pain-like behavior, reduced proprioception and coordination, and increased anxiety-like behavior post-bSCI, which underlines the translational capabilities of this model. While further research is vital to understand better the intrinsic and synergistic chemical and mechanical factors driving the migration of stem cells after traumatic injury, increased endogenous stem cell populations at the injury site indicate that stem cell-based treatments in patients suffering from bSCI could prove beneficial.

爆炸诱发脊髓损伤急性期内源性干细胞群的变化
背景:爆炸诱发的脊髓损伤(bSCI)在军事人群中十分普遍,经常导致不可逆转的脊髓组织损伤,表现为感觉运动和自主神经系统功能障碍。事实证明,bSCI 的临床恢复是多因素的,因为它在很大程度上取决于组织环境中众多细胞群的功能以及广泛持续的炎症过程。这种不同的恢复过程被认为是由于损伤后 72 小时后脊髓不可逆转的损伤所致。由于干细胞具有增殖特性,能够促进神经再生、神经保护、轴突再髓鞘化以及调节免疫和炎症反应,因此治疗脊髓损伤的干细胞疗法已被研究了很长时间。因此,本研究假设,损伤后功能受损是由于损伤部位缺乏特定的外胚层和神经干细胞群活动:本研究旨在利用临床前胸腰椎损伤模型,通过评估各种干细胞标记物的免疫组化染色密度,阐明内源性干细胞模式的变化。分析在爆炸暴露后24、48和72小时进行。还进行了行为测试,以评估感觉和机械功能:结果:bSCI 72 小时后,脊髓组织胸腰部的下列分化簇(CD)标记物 CD105、CD45、CD133 和波形蛋白、Nanog 同源盒(NANOG)以及性别决定区 Y HMG-box 2(SOX2)阳性细胞群显著升高,八聚体结合转录因子 4(OCT4)也呈上升趋势(p < 0.05)。行为分析表明,在损伤后48小时和72小时,后肢爪退出阈值显著下降,运动也发生了变化(p < 0.05):结论:损伤后胸腰部间充质干细胞、多能干细胞和神经干细胞群明显增加,这表明干细胞群的迁移模式可能会对bSCI发生改变。行为缺陷与军事人员经历的行为缺陷一致,如损伤后疼痛样行为增加、本体感觉和协调能力降低以及焦虑样行为增加,这强调了该模型的转化能力。虽然进一步的研究对更好地了解创伤后驱动干细胞迁移的内在和协同化学与机械因素至关重要,但损伤部位内源性干细胞群的增加表明,基于干细胞的治疗可能对脑损伤患者有益。
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来源期刊
CiteScore
2.80
自引率
5.60%
发文量
173
审稿时长
2 months
期刊介绍: JIN is an international peer-reviewed, open access journal. JIN publishes leading-edge research at the interface of theoretical and experimental neuroscience, focusing across hierarchical levels of brain organization to better understand how diverse functions are integrated. We encourage submissions from scientists of all specialties that relate to brain functioning.
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