title: Association between toll-like receptor 4 expression and neural stem cell proliferation in the hippocampus following traumatic brain injury in mice.
abstract: Whether or how neural stem cells (NSCs) respond to toll-like receptor 4 (TLR4) in an inflammatory environment caused by traumatic brain injury (TBI) has not been understood. In the present study, association between TLR4 expression and NSCs proliferation in the hippocampus was investigated in a mouse model of TBI using controlled cortical impact (CCI). Hippocampal proliferating cells were labeled with the thymidine analog 5-bromo-2-deoxyuridine (BrdU). In order to identify NSCs, the proliferating cells were further co-labeled with BrdU/sex determination region of Y chromosome related high mobility group box gene 2 (SOX2). Morphological observation on the expression of BrdU, SOX2, and TLR4 in the hippocampus was performed by inmmunofluorescence (IF). Relative quantification of TLR4 expression at the protein and mRNA level was performed using Western blotting and real-time polymerase chain reaction (PCR). It was observed that BrdU+/SOX2+cells accounted for 95.80%±7.91% among BrdU+ cells; several BrdU+ cells and SOX2+ cells in the hippocampus were also TLR4-positive post injury, and that BrdU+ cell numbers, together with TLR4 expression at either protein or mRNA level, increased significantly in TBI mice over 1, 3, 7, 14, and 21 days survivals and changed in a similar temporal pattern with a peak at 3 day post-injury. These results indicate that hippocampal proliferating cells (suggestive of NSCs) expressed TLR4, and that there was a potential association between increased expression of TLR4 and the proliferation of NSCs post TBI. It is concluded that hippocampal TLR4 may play a potential role in endogenous neurogenesis after TBI.
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. chinayeyuqin@163.com.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. xuhy@fmmu.edu.cn.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. heartychang@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. lizewyl@163.com.
authors.forename: Ze
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. sjwkjyf@126.com.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. hexiaos@fmmu.edu.cn.
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Baylor Scott & White Health, Temple, TX 76508, USA. JHUANG@sw.org.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Huang
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D049109:Cell Proliferation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4