Thrombospondin-1 Gene Deficiency Worsens the Neurological Outcomes of Traumatic Brain Injury in Mice
| Autor: | Chongjie Cheng, Changhong Xing, Yinghua Jiang, Song Zhao, Xiaochuan Sun, Xiaoying Wang, Michael J. Whalen, Yong-Guang Yang, Zhengbu Liao, Zhanyang Yu, Eng H. Lo |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Time Factors Morris water navigation task Thrombospondin 1 angiogenesis Mice chemistry.chemical_compound Cognition 0302 clinical medicine synaptogenesis Neurotrophic factors Medicine Evans Blue Cerebral Cortex Mice Knockout biology traumatic brain injury General Medicine Up-Regulation medicine.anatomical_structure Blood-Brain Barrier Cerebral cortex medicine.symptom Research Paper medicine.medical_specialty Thromspondin-1 (TSP-1) Traumatic brain injury Synaptophysin Neovascularization Physiologic blood-brain-barrier Lesion 03 medical and health sciences Internal medicine Angiopoietin-1 Animals Maze Learning Brain-derived neurotrophic factor neurological severity score (NSS) business.industry Brain-Derived Neurotrophic Factor Recovery of Function medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology nervous system chemistry morris water maze (MWM) Brain Injuries biology.protein business Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Medical Sciences |
| ISSN: | 1449-1907 |
| Popis: | 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. 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. 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. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|