2. Academic Validation
  3. Bexarotene promotes microglia/macrophages - Specific brain - Derived Neurotrophic factor expression and axon sprouting after traumatic brain injury

Bexarotene promotes microglia/macrophages - Specific brain - Derived Neurotrophic factor expression and axon sprouting after traumatic brain injury

  • Exp Neurol. 2020 Dec;334:113462. doi: 10.1016/j.expneurol.2020.113462.
Junchi He 1,  Yike Huang 2,  Han Liu 1,  Xiaochuan Sun 1,  Jingchuan Wu 1,  Zhaosi Zhang 1,  Liu Liu 1,  Chao Zhou 1,  Shaoqiu Jiang 3,  Zhijian Huang 1,  Jianjun Zhong 1,  Zongduo Guo 1,  Li Jiang 1,  Chongjie Cheng 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of Ophthalmology, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, China.
  • 3 Department of Ophthalmology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 4 Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
PMID: 32916173 DOI: 10.1016/j.expneurol.2020.113462
Abstract

Traumatic brain injury (TBI) has been regarded as one of the leading cause of injury-related death and disability. White matter injury after TBI is characterized by axon damage and demyelination, resulting in neural network impairment and neurological deficit. Brain-derived neurotrophic factor (BDNF) can promote white matter repair. The activation of Peroxisome Proliferator-activated Receptor gamma (PPARγ) has been reported to promote microglia/macrophages towards anti-inflammatory state and therefore to promote axon regeneration. Bexarotene, an agonist of retinoid X receptor (RXR), can activate RXR/PPARγ heterodimers. The aim of the present study was to identify the effect of bexarotene on BDNF in microglia/macrophages and axon sprouting after TBI in mice. Bexarotene was administered intraperitoneally in C57BL/6 mice undergoing controlled cortical impact (CCI). PPARγ dependency was determined by intraperitoneal administration of a PPARγ Antagonist T0070907. We found that bexarotene promoted axon regeneration indicated by increased growth associated protein 43 (GAP43) expression, myelin basic protein (MBP) expression, and biotinylated dextran amine (BDA)+ axon sprouting. Bexarotene also increased microglia/macrophages-specific brain derived neurotrophic factor (BDNF) expression after TBI. In addition, bexarotene reduced the number of pro-inflammatory microglia/macrophages while increased the number of anti-inflammatory microglia/macrophages after TBI. Moreover, bexaortene inhibited pro-inflammatory cytokine secretion. In addition, bexarotene treatment improved neurological scores and cognitive function of CCI-injured mice. These effects of bexarotene were partially abolished by T0070907. In conclusion, bexarotene promotes axon sprouting, increases microglia/macrophages-specific BDNF expression, and induces microglia/macrophages from a pro-inflammatory state towards an anti-inflammatory one after TBI at least partially in a PPARγ-dependent manner.

Keywords

Axon sprouting; Brain derived neurotrophic factor; Microglia/macrophages; Traumatic brain injury.

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