TY  - JOUR
PY  - 2017//
TI  - Thrombospondin-1 gene deficiency worsens the neurological outcomes of traumatic brain injury in mice
JO  - International journal of medical sciences
A1  - Cheng, Chongjie
A1  - Yu, Zhanyang
A1  - Zhao, Song
A1  - Liao, Zhengbu
A1  - Xing, Changhong
A1  - Jiang, Yinghua
A1  - Yang, Yong-Guang
A1  - Whalen, Michael J.
A1  - Lo, Eng H.
A1  - Sun, Xiaochuan
A1  - Wang, Xiaoying
SP  - 927
EP  - 936
VL  - 14
IS  - 10
N2  - BACKGROUND: Thrombospondin-1 (TSP-1) is an extracellular matrix protein that plays multiple physiological and pathophysiological roles in the brain. Experimental reports suggest that TSP-1 may have an adverse role in neuronal function recovery under certain injury conditions. However, the roles of TSP-1 in traumatic brain injury (TBI) have not been elucidated. In this study we for the first time investigated the roles of TSP-1 in a controlled cortical impact (CCI) model of TBI in TSP-1 knockout (TSP-1 KO) and wild type (WT) mice. <br><br>METHODS: We examined blood brain-barrier (BBB) damage using at 1 day post-TBI by measuring Evans Blue leakage, and neurological functional recovery at 3 weeks post-TBI by measuring neurological severity score (NSS), wire gripping, corner test and Morris Water Maze (MWM). Mechanistically, we quantified pro-angiogenic biomarkers including cerebral vessel density, vascular endothelial growth factors (VEGF) and angiopoietin-1 (Ang-1) protein expression, synaptic biomarker synaptophysin, and synaptogenesis marker brain-derived neurotrophic factor (BDNF) protein expression in contralateral and ipsilateral (peri-lesion) cortex at 21 days after TBI using immunohistochemistry and Western Blot. <br><br>RESULTS: TSP-1 is upregulated at early phase of TBI in WT mice. Compared to WT mice, TSP-1 KO (1) significantly worsened TBI-induced BBB leakage at 1 day after TBI; (2) had similar lesion size as WT mice at 3 weeks after TBI; (3) exhibited a significantly worse neurological deficits in motor and cognitive functions; (4) had no significant difference in cerebral vessel density, but significant increase of VEGF and Ang-1 protein expressions in peri-lesion cortex; (5) significantly increased BDNF but not synaptophysin protein level in peri-lesion cortex compared to sham, but both synaptophysin and BDNF expressions were significantly decreased in contralateral cortex compared to WT. <br><br>CONCLUSION: Our results suggest that TSP-1 may be beneficial for maintaining BBB integrity in the early phase and functional recovery in late phase after TBI. The molecular mechanisms of TSP-1 in early BBB pathophysiology, and long-term neurological function recovery after TBI need to be further investigated.<p />  <p>Language: en</p>
LA  - en
SN  - 1449-1907
UR  - http://dx.doi.org/10.7150/ijms.18812
ID  - ref1
ER  -