Affiliations: Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Correspondence:
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Correspondence to: Lin Zhang, Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth
People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 600 Yishan Road, Xuhui District, Shanghai
200233, China. Tel.: +86 18930170167; E-mail: [email protected].
Abstract: Traumatic brain injury (TBI), a brain disorder that causes death and long-term disability in humans, is increasing in prevalence, though there is a lack of protective or therapeutic strategies for mitigating the damage after TBI and for preserving neurological functionality. Microglia cells play a key role in neuroinflammation following TBI, but their regulation and polarization by a member of the vascular endothelial growth factor (VEGF) family, VEGF-C, is unknown. Here, we show that VEGF-C induced M2 polarization in a murine microglia cell line, BV-2, in vitro, by a mechanism that required signaling from its unique receptor, VEGF receptor 3 (VEGFR3). Moreover, in a TBI model in rats, VEGF-C administration induced M2 polarization of microglia cells, significantly improved motor deficits after experimental TBI, and significantly improved neurological function following TBI, likely through a reduction in cell apoptosis. Together, our data reveal a previously unknown role of VEGF-C/VEGFR3 signaling in the regulation of post-TBI microglia cell polarization, which appears to be crucial for recovery from TBI.
