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Vascular endothelial growth factor is neuroprotective against ischemic brain injury by inhibiting scavenger receptor A expression on microglia
Author(s) -
Xu Zheng,
Han Kaiwei,
Chen Jigang,
Wang Chunhui,
Dong Yan,
Yu Mingkun,
Bai Rulin,
Huang Chenguang,
Hou Lijun
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14108
Subject(s) - neuroprotection , microglia , scavenger receptor , scavenger , ischemic injury , pharmacology , free radical scavenger , medicine , neuroscience , chemistry , inflammation , ischemia , biology , oxidative stress , biochemistry , cholesterol , antioxidant , lipoprotein
Vascular endothelial growth factor ( VEGF ) is a secreted mitogen associated with angiogenesis. VEGF has long been thought to be a potent neurotrophic factor for the survival of spinal cord neurons. However, the role of VEGF in the regulation of ischemic brain injury remains unclear. In this study, rats were subjected to MCAO (middle cerebral artery occlusion) followed by intraperitoneal injection of VEGF 165 (10 mg/kg) immediately after surgery and once daily until the day 10. The expression of target genes was assayed using qPCR , western blot and immunofluorescence to investigate the role of VEGF165 in regulating ischemic brain injury. We found that VEGF 165 significantly inhibited MCAO‐induced up‐regulation of Scavenger receptor class A ( SR ‐A) on microglia in a VEGFR 1‐dependent manner. VEGF 165 inhibited lipopolysaccharide (LPS)‐induced expression of proinflammatory cytokines IL ‐1β, tumor necrosis factor alpha ( TNF ‐α) and iNOS in microglia. More importantly, the role of VEGF 165 in inhibiting neuroinflammation is partially abolished by SR ‐A over‐expression. SR ‐A further reduced the protective effect of VEGF 165 in ischemic brain injury. These data suggest that VEGF 165 suppresses neuroinflammation and ischemic brain injury by inhibiting SR ‐A expression, thus offering a new target for prevention of ischemic brain injury.