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发育中和成熟大鼠对急性脊髓损伤的细胞反应差异凸显了炎症反应的潜在重要性。

Differences in the Cellular Response to Acute Spinal Cord Injury between Developing and Mature Rats Highlights the Potential Significance of the Inflammatory Response.

作者信息

Sutherland Theresa C, Mathews Kathryn J, Mao Yilin, Nguyen Tara, Gorrie Catherine A

机构信息

Neural Injury Research Unit, School of Medical and Molecular Bioscience, University of Technology Sydney Ultimo, NSW, Australia.

Discipline of Biomedical Sciences and Brain and Mind Centre, Sydney Medical School, The University of Sydney Sydney, NSW, Australia.

出版信息

Front Cell Neurosci. 2017 Jan 13;10:310. doi: 10.3389/fncel.2016.00310. eCollection 2016.

Abstract

There exists a trend for a better functional recovery from spinal cord injury (SCI) in younger patients compared to adults, which is also reported for animal studies; however, the reasons for this are yet to be elucidated. The post injury tissue microenvironment is a complex milieu of cells and signals that interact on multiple levels. Inflammation has been shown to play a significant role in this post injury microenvironment. Endogenous neural progenitor cells (NPC), in the ependymal layer of the central canal, have also been shown to respond and migrate to the lesion site. This study used a mild contusion injury model to compare adult (9 week), juvenile (5 week) and infant (P7) Sprague-Dawley rats at 24 h, 1, 2, and 6 weeks post-injury ( = 108). The innate cells of the inflammatory response were examined using counts of ED1/IBA1 labeled cells. This found a decreased inflammatory response in the infants, compared to the adult and juvenile animals, demonstrated by a decreased neutrophil infiltration and macrophage and microglial activation at all 4 time points. Two other prominent cellular contributors to the post-injury microenvironment, the reactive astrocytes, which eventually form the glial scar, and the NPC were quantitated using GFAP and Nestin immunohistochemistry. After SCI in all 3 ages there was an obvious increase in Nestin staining in the ependymal layer, with long basal processes extending into the parenchyma. This was consistent between age groups early post injury then deviated at 2 weeks. The GFAP results also showed stark differences between the mature and infant animals. These results point to significant differences in the inflammatory response between infants and adults that may contribute to the better recovery indicated by other researchers, as well as differences in the overall injury progression and cellular responses. This may have important consequences if we are able to mirror and manipulate this response in patients of all ages; however much greater exploration in this area is required.

摘要

与成年患者相比,年轻患者脊髓损伤(SCI)后的功能恢复趋势更佳,动物研究也有类似报道;然而,其原因尚待阐明。损伤后组织微环境是一个由细胞和信号构成的复杂环境,它们在多个层面相互作用。炎症已被证明在这种损伤后微环境中起重要作用。中央管室管膜层中的内源性神经祖细胞(NPC)也已被证明会对损伤部位做出反应并迁移至该部位。本研究使用轻度挫伤损伤模型,比较成年(9周龄)、幼年(5周龄)和幼龄(P7)的Sprague-Dawley大鼠在损伤后24小时、1周、2周和6周时的情况(每组n = 108)。通过计数ED1/IBA1标记的细胞来检查炎症反应的固有细胞。结果发现,与成年和幼年动物相比,幼龄动物的炎症反应减弱,在所有4个时间点均表现为中性粒细胞浸润减少以及巨噬细胞和小胶质细胞活化减弱。使用GFAP和巢蛋白免疫组织化学对损伤后微环境的另外两个重要细胞成分——最终形成胶质瘢痕的反应性星形胶质细胞和NPC进行定量分析。在所有3个年龄组的脊髓损伤后,室管膜层中的巢蛋白染色均明显增加,其长的基底突起延伸至实质内。损伤后早期各年龄组之间情况一致,但在2周时出现差异。GFAP结果也显示成熟动物和幼龄动物之间存在明显差异。这些结果表明,幼龄和成年动物在炎症反应方面存在显著差异,这可能是其他研究人员所指出的幼龄动物恢复更好的原因,同时也表明在整体损伤进展和细胞反应方面存在差异。如果我们能够在所有年龄段的患者中模拟和控制这种反应,可能会产生重要影响;然而,该领域还需要进行更多的探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba86/5233684/7ed8570c6ecd/fncel-10-00310-g0001.jpg

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