Effects and Mechanism of Action of Neonatal Versus Adult Astrocytes on Neural Stem Cell Proliferation After Traumatic Brain Injury

• Published in: Stem cells (Dayton, Ohio) Vol. 37; no. 10; pp. 1344 - 1356
• Main Authors: Dai, Yong, Sun, Feifan, Zhu, Hui, Liu, Qianqian, Xu, Xide, Gong, Peipei, Jiang, Rui, Jin, Guohua, Qin, Jianbing, Chen, Jian, Zhang, Xinghua, Shi, Wei
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.10.2019; Oxford University Press
• Subjects: 1-Phosphatidylinositol 3-kinase; Adults; AKT protein; Astrocytes; Brain; Cell proliferation; Conditioning; Differentiation; Epidermal growth factor; Growth factors; Head injuries; Injury prevention; Lipopolysaccharides; Mass spectrometry; Mass spectroscopy; Microenvironment; Neonates; Neural stem cells; Proliferation; Repair; Stem cell transplantation; Stem cells; Tenascin; Therapeutic applications; Traumatic brain injury; Neural stem cells; Microenvironment; Proliferation; Differentiation; Astrocytes
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.3060

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. Stem Cells 2019;37:1344–1356 Neonatal rat astrocytes can significantly promote the proliferation of neural stem cells, compared with adult rat astrocytes. We analyzed and screened for a protein, Tenascin‐C (TNC), which was highly expressed in the neonatal astrocytes, but poorly expressed in the adult astrocytes. TNC can bind to the NSC surface epidermal growth factor receptor, and promote proliferation through the PI3K‐AKT pathway.