Cell based therapy reduces secondary damage and increases extent of microglial activation following cortical injury.
Cell based therapy reduces secondary damage and increases extent of microglial activation following cortical injury.
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基于细胞的治疗减少了继发性损伤并增加了皮质损伤后小胶质细胞的活化程度。
DOI：
10.1016/j.brainres.2019.04.015
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发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
Moore,TaraL
中科院分区：
文献类型：
--
作者：
Orczykowski,MaryE;Calderazzo,SamanthaM;Shobin,Eli;Pessina,MonicaA;Oblak,AdrianL;Finklestein,SethP;Kramer,BrianC;Mortazavi,Farzad;Rosene,DouglasL;Moore,TaraL
皮质损伤在脑内引起长期的细胞毒性和细胞保护机制，这些途径的平衡可以决定个体的功能结果。活性氧的产生、铁的积累以及细胞膜和髓鞘的过氧化会加剧细胞毒性。目前还没有神经修复疗法来帮助平衡皮质损伤后的细胞毒性和细胞保护机制。基于细胞的治疗是一种新兴的治疗方法，它可能在免疫调节、减少二次损伤和重组存活结构方面发挥作用。我们之前在我们的非人类灵长类动物皮质损伤模型中评估了人脐组织衍生细胞(HUTC)，该模型局限于初级运动皮质的手部区域。与车辆对照组相比，全身hUTC治疗可显著提高精细运动功能的恢复。在这里，我们研究了hUTC治疗减少氧化损伤和铁积累并增加小胶质细胞对皮质损伤反应的程度的假说。为了验证这一点，对这些猴子的大脑切片进行了免疫组织化学处理，以定量氧化损伤(4-HNE)和激活的小胶质细胞(LN3)，并使用普鲁士蓝来定量铁。HUTC治疗的受试者表现出明显的减少了皮层下白质的氧化损伤和周围区域的铁蓄积，并显着增加了白质通路上激活的小胶质细胞的程度。皮损周围铁蓄积增加与更大的皮损周围氧化损伤和更大的重建病变体积相关。这些发现支持这样的假设，即皮质损伤后24 小时全身性给予hUTC降低了细胞毒反应，同时增加了小胶质细胞的激活程度。
Cortical injury elicits long-term cytotoxic and cytoprotective mechanisms within the brain and the balance of these pathways can determine the functional outcome for the individual. Cytotoxicity is exacerbated by production of reactive oxygen species, accumulation of iron, and peroxidation of cell membranes and myelin. There are currently no neurorestorative treatments to aid in balancing the cytotoxic and cytoprotective mechanisms following cortical injury. Cell based therapies are an emerging treatment that may function in immunomodulation, reduction of secondary damage, and reorganization of surviving structures. We previously evaluated human umbilical tissue-derived cells (hUTC) in our non-human primate model of cortical injury restricted to the hand area of primary motor cortex. Systemic hUTC treatment resulted in significantly greater recovery of fine motor function compared to vehicle controls. Here we investigate the hypothesis that hUTC treatment reduces oxidative damage and iron accumulation and increases the extent of the microglial response to cortical injury. To test this, brain sections from these monkeys were processed using immunohistochemistry to quantify oxidative damage (4-HNE) and activated microglia (LN3), and Prussian Blue to quantify iron. hUTC treated subjects exhibited significantly reduced oxidative damage in the sublesional white matter and iron accumulation in the perilesional area as well as a significant increase in the extent of activated microglia along white matter pathways. Increased perilesional iron accumulation was associated with greater perilesional oxidative damage and larger reconstructed lesion volume. These findings support the hypothesis that systemic hUTC administered 24 h after cortical damage decreases the cytotoxic response while increasing the extent of microglial activation.