Effects and Mechanism of Action of Neonatal Versus Adult Astrocytes on Neural Stem Cell Proliferation After Traumatic Brain Injury
Effects and Mechanism of Action of Neonatal Versus Adult Astrocytes on Neural Stem Cell Proliferation After Traumatic Brain Injury
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新生儿与成人星形胶质细胞对脑外伤后神经干细胞增殖的影响及作用机制
DOI：
10.1002/stem.3060
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发表时间：
2019-08-05
期刊：
影响因子：
5.2
通讯作者：
Shi, Wei
中科院分区：
文献类型：
--
作者：
Dai, Yong;Sun, Feifan;Shi, Wei
由于创伤性脑损伤（TBI）后脑组织的自我再生能力有限，内源性神经干细胞（NSCs）的动员是一个热门的研究课题。在临床上，成人与新生儿的神经原性能力差异很大，这可能与神经干细胞的功能差异有关。最近的研究表明，星形胶质细胞分泌的分子在NSC的命运决定中起重要作用。在这项研究中，条件培养基（CM）来自新生或成年大鼠星形胶质细胞，这是未经刺激或刺激的脂多糖（LPS），制备处理神经干细胞。我们的结果显示，与成年大鼠星形胶质细胞相比，无论是否受到LPS刺激，新生大鼠星形胶质细胞都能显著促进NSCs的增殖。此外，我们使用质谱法检测各组CM的成分。我们分析并筛选了一种蛋白质，Tenascin-C（TNC），它在新生儿组中高度表达，但在成人组中表达较差。我们发现TNC可以与NSC表面的表皮生长因子受体结合，并通过PI 3 K-AKT途径促进体外NSC的增殖。此外，我们在体内证实了TNC可以通过增强内源性NSC的增殖来促进TBI大鼠模型中的损伤修复。我们相信，这些发现提供了一个机制的理解，为什么新生儿表现出更好的神经再生能力比成人。这也为TBI后的损伤修复提供了潜在的未来治疗靶点TNC。
Due to the limited capacity of brain tissue to self-regenerate after traumatic brain injury (TBI), the mobilization of endogenous neural stem cells (NSCs) is a popular research topic. In the clinic, the neurogenic abilities of adults versus neonates vary greatly, which is likely related to functional differences in NSCs. Recent studies have demonstrated that the molecules secreted from astrocytes play important roles in NSC fate determination. In this study, conditioned media (CM) derived from neonatal or adult rat astrocytes, which were unstimulated or stimulated by lipopolysaccharide (LPS), were prepared to treat NSCs. Our results revealed that neonatal rat astrocytes can significantly promote the proliferation of NSCs, compared with adult rat astrocytes, regardless of whether or not they were stimulated by LPS. Furthermore, we used mass spectrometry to detect the constituents of the CM from each group. We analyzed and screened for a protein, Tenascin-C (TNC), which was highly expressed in the neonatal group but poorly expressed in the adult group. We found that TNC can bind to the NSC surface epidermal growth factor receptor and promote proliferation through the PI3K-AKT pathway in vitro. Additionally, we confirmed in vivo that TNC can promote damage repair in a rat model of TBI, through enhancing the proliferation of endogenous NSCs. We believe that these findings provide a mechanistic understanding of why neonates show better neuroregenerative abilities than adults. This also provides a potential future therapeutic target, TNC, for injury repair after TBI.