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Int. J. Mol. Sci. 2014, 15(7), 12651-12664; doi:10.3390/ijms150712651

Association between Toll-Like Receptor 4 Expression and Neural Stem Cell Proliferation in the Hippocampus Following Traumatic Brain Injury in Mice

1
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
2
Department of Neurosurgery, Second Affiliated Hospital of Hunan Normal University (PLA 163 Hospital), Changsha 410000, China
3
Department of Neurosurgery, Baylor Scott & White Health, Temple, TX 76508, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 30 April 2014 / Revised: 3 July 2014 / Accepted: 4 July 2014 / Published: 17 July 2014
(This article belongs to the Special Issue Neurological Injuries’ Monitoring, Tracking and Treatment)
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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. View Full-Text
Keywords: toll-like receptor 4 (TLR4); neural stem cells (NSCs); hippocampus; traumatic brain injury (TBI); mice toll-like receptor 4 (TLR4); neural stem cells (NSCs); hippocampus; traumatic brain injury (TBI); mice
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MDPI and ACS Style

Ye, Y.; Xu, H.; Zhang, X.; Li, Z.; Jia, Y.; He, X.; Huang, J.H. Association between Toll-Like Receptor 4 Expression and Neural Stem Cell Proliferation in the Hippocampus Following Traumatic Brain Injury in Mice. Int. J. Mol. Sci. 2014, 15, 12651-12664.

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