Department of Neurosurgery Tianjin Medical University General Hospital Heping District Tianjin China.
Tianjin Neurological Institute Tianjin China.
Brain Behav. 2017 Oct 3;7(11):e00827. doi: 10.1002/brb3.827. eCollection 2017 Nov.
Traumatic brain injury (TBI) remains a leading cause of disability and death among young people in China. Unfortunately, no specific pharmacological agents to block the progression of secondary brain injury have been approved for clinical treatment. Recently, neuroprotective effects of erythropoietin (EPO) have been demonstrated in addition to its principal function in erythropoiesis, and hence it is viewed as a potential drug for TBI. In this study, we have investigated the neuroprotective effects of EPO associated with immune/inflammatory modulation in a mouse experimental TBI model.
EPO (5000 U/kg body weight, i.p.) was injected at 1 hr, 1, 2, and 3 days after TBI, and its effect on cognitive function, brain edema, immune/inflammatory cells including regulatory T cells (Tregs), neutrophils, CD3 T cells, and microglia, cytokines including interleukin-10 (IL-10), transforming growth factor-β (TGF-β), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were evaluated at different time points after treatment.
EPO treatment significantly decreased brain edema and improved cognitive function when compared to Saline-treated mice (<.05). EPO treatment also significantly increased Tregs level in spleen and injured brain tissue as well as significantly reduced the infiltration and activation of immune/inflammatory cells (neutrophils, CD3T cells, and microglia) in the injured hemisphere compared to Saline-treated control animals (<.05). In addition, ELISA analysis demonstrated that EPO treatment increased the expression of anti-inflammatory cytokine IL-10, but decreased the expression of proinflammatory cytokine IL-1β and TNF-α in the injured brain tissue (<.05).
These findings suggest that EPO could improve neurological and cognitive functional outcomes as well as regulate immune/inflammatory reaction in TBI.
在中国，创伤性脑损伤（TBI）仍然是导致年轻人残疾和死亡的主要原因。不幸的是，没有专门用于阻止继发性脑损伤进展的药物被批准用于临床治疗。最近，研究表明促红细胞生成素（EPO）除了其在红细胞生成中的主要功能外，还具有神经保护作用，因此被认为是一种治疗 TBI 的潜在药物。在本研究中，我们研究了 EPO 对免疫/炎症调节的神经保护作用及其在小鼠实验性 TBI 模型中的作用。
EPO（5000 U/kg 体重，腹腔注射）于 TBI 后 1 小时、1 天、2 天和 3 天注射，评估其对认知功能、脑水肿、免疫/炎症细胞（调节性 T 细胞[Tregs]、中性粒细胞、CD3 T 细胞和小胶质细胞）和细胞因子（白细胞介素 10 [IL-10]、转化生长因子-β[TGF-β]、白细胞介素 1β[IL-1β]和肿瘤坏死因子-α[TNF-α]）的影响在治疗后不同时间点。
与生理盐水治疗的小鼠相比，EPO 治疗显著降低了脑水肿并改善了认知功能（<0.05）。EPO 治疗还显著增加了脾脏和损伤脑组织中的 Tregs 水平，并显著减少了损伤半球中免疫/炎症细胞（中性粒细胞、CD3T 细胞和小胶质细胞）的浸润和激活与生理盐水治疗的对照动物相比（<0.05）。此外，ELISA 分析表明，EPO 治疗增加了抗炎细胞因子 IL-10 的表达，但降低了损伤脑组织中促炎细胞因子 IL-1β 和 TNF-α 的表达（<0.05）。
这些发现表明，EPO 可改善 TBI 中的神经和认知功能，并调节免疫/炎症反应。
