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Acute and non-resolving inflammation associate with oxidative injury after human spinal cord injury.
人脊髓损伤后急性非消退炎症与氧化损伤相关。
- 影响因子:0
- DOI:10.1093/brain/awaa360
- 作者列表:"Zrzavy T","Schwaiger C","Wimmer I","Berger T","Bauer J","Butovsky O","Schwab JM","Lassmann H","Höftberger R
- 发表时间:2021-02-12
Abstract
:Traumatic spinal cord injury is a devastating insult followed by progressive cord atrophy and neurodegeneration. Dysregulated or non-resolving inflammatory processes can disturb neuronal homeostasis and drive neurodegeneration. Here, we provide an in-depth characterization of innate and adaptive inflammatory responses as well as oxidative tissue injury in human traumatic spinal cord injury lesions compared to non-traumatic control cords. In the lesion core, microglia were rapidly lost while intermediate (co-expressing pro- as well as anti-inflammatory molecules) blood-borne macrophages dominated. In contrast, in the surrounding rim, TMEM119+ microglia numbers were maintained through local proliferation and demonstrated a predominantly pro-inflammatory phenotype. Lymphocyte numbers were low and mainly consisted of CD8+ T cells. Only in a subpopulation of patients, CD138+/IgG+ plasma cells were detected, which could serve as candidate cellular sources for a developing humoral immunity. Oxidative neuronal cell body and axonal injury was visualized by intracellular accumulation of amyloid precursor protein (APP) and oxidized phospholipids (e06) and occurred early within the lesion core and declined over time. In contrast, within the surrounding rim, pronounced APP+/e06+ axon-dendritic injury of neurons was detected, which remained significantly elevated up to months/years, thus providing mechanistic evidence for ongoing neuronal damage long after initial trauma. Dynamic and sustained neurotoxicity after human spinal cord injury might be a substantial contributor to (i) an impaired response to rehabilitation; (ii) overall failure of recovery; or (iii) late loss of recovered function (neuro-worsening/degeneration).
摘要
: 创伤性脊髓损伤是一种毁灭性的损害,随后是进行性脊髓萎缩和神经变性。失调或非分解的炎症过程可以干扰神经元稳态并驱动神经变性。在这里,与非创伤性对照索相比,我们提供了人类创伤性脊髓损伤病变中先天和适应性炎症反应以及氧化组织损伤的深入表征。在病变核心中,小胶质细胞迅速丢失,而中间 (共表达促炎分子和抗炎分子) 血源性巨噬细胞占优势。相反,在周围的边缘中,通过局部增殖维持TMEM119 + 小胶质细胞数量,并表现出主要的促炎表型。淋巴细胞数量低,主要由CD8 + T细胞组成。仅在患者亚群中检测到CD138 +/IgG + 浆细胞,其可作为发展体液免疫的候选细胞源。氧化性神经元细胞体和轴突损伤通过淀粉样前体蛋白 (APP) 和氧化磷脂 (e06) 的细胞内积累显现,并且在病变核心内早期发生,并且随着时间的推移而下降。相比之下,在周围的边缘内,检测到神经元的明显的APP +/e06 + 轴突-树突损伤,其保持显著升高至数月/年,因此提供了在初始创伤后很长时间内持续神经元损伤的机制证据。人脊髓损伤后的动态和持续神经毒性可能是 (i) 康复反应受损; (ii) 恢复的总体失败; 或 (iii) 恢复功能的晚期丧失 (神经恶化/退化) 的主要原因。
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