Department of Neurology, Xinqiao Hospital, The Army Medical University, Third Military Medical University, Chongqing 400037, China.
Department of Neurology, Xinqiao Hospital, The Army Medical University, Third Military Medical University, Chongqing 400037, China
Biosci Rep. 2019 May 17;39(5). doi: 10.1042/BSR20190537. Print 2019 May 31.
Aging has been shown to contribute to both the declined biofunctions of aging brain and aggravation of acute brain damage, and the former could be reversed by young plasma. These results suggest that young plasma treatment may also reduce the acute brain damage induced by intracerebral hemorrhage (ICH). In the present study, we first found that the administration of young plasma significantly reduced the mortality and neurological deficit score in aging ICH rodents, which might be due to the decreased brain water content, damaged neural cells, and increased survival neurons around the perihematomal brain tissues. Then, proteomics analysis was used to screen out the potential neuroprotective circulating factors and the results showed that many factors were changed in health human plasma among young, adult, and old population. Among these significantly changed factors, the plasma insulin-like growth factor 1 (IGF-1) level was significantly decreased with age, which was further confirmed both in human and rats detected by ELISA. Additionally, the brain IGF-1 protein level in aging ICH rats was markedly decreased when compared with young rats. Interestingly, the relative decreased brain IGF-1 level was reversed by the treatment of young plasma in aging ICH rats, while the mRNA level was non-significantly changed. Furthermore, the IGF-1 administration significantly ameliorated the acute brain injury in aging ICH rats. These results indicated that young circulating factors, like IGF-1, may enter brain tissues to exert neuroprotective effects, and young plasma may be considered as a novel therapeutic approach for the clinical treatment of aging-related acute brain injury.
衰老是导致衰老大脑生物功能下降和急性脑损伤加重的原因之一,而年轻血浆可以逆转前者。这些结果表明,年轻血浆治疗可能也会减轻脑出血(ICH)引起的急性脑损伤。在本研究中,我们首先发现,年轻血浆的给药显著降低了衰老 ICH 啮齿动物的死亡率和神经功能缺损评分,这可能是由于脑水含量降低、神经细胞受损以及围绕血肿周围的存活神经元增加所致。然后,蛋白质组学分析被用来筛选出潜在的神经保护循环因子,结果表明,在年轻、成年和老年人群中,健康人血浆中有许多因子发生了变化。在这些显著变化的因子中,血浆胰岛素样生长因子 1(IGF-1)水平随年龄增长而显著降低,这在人类和大鼠中通过 ELISA 进一步得到证实。此外,与年轻大鼠相比,衰老 ICH 大鼠大脑中的 IGF-1 蛋白水平明显降低。有趣的是,年轻血浆处理可逆转衰老 ICH 大鼠大脑中相对降低的 IGF-1 水平,而其 mRNA 水平没有显著变化。此外,IGF-1 给药可显著改善衰老 ICH 大鼠的急性脑损伤。这些结果表明,年轻的循环因子,如 IGF-1,可能进入脑组织发挥神经保护作用,年轻血浆可能被认为是治疗与衰老相关的急性脑损伤的一种新的治疗方法。