The Small-Molecule TrkB Agonist 7, 8-Dihydroxyflavone Decreases Hippocampal Newborn Neuron Death after Traumatic Brain Injury

Liang Chen, Xiang Gao, Shu Zhao, Weipeng Hu, Jinhui Chen

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Previous studies in rodents have shown that after a moderate traumatic brain injury (TBI) with a controlled cortical impact (CCI) device, the adult-born immature granular neurons in the dentate gyrus are the most vulnerable cell type in the hippocampus. There is no effective approach for preventing immature neuron death after TBI. We found that tyrosine-related kinase B (TrkB), a receptor of brain-derived neurotrophic factor (BDNF), is highly expressed in adult-born immature neurons. We determined that the small molecule imitating BDNF, 7, 8-dihydroxyflavone (DHF), increased phosphorylation of TrkB in immature neurons both in vitro and in vivo. Pretreatment with DHF protected immature neurons from excitotoxicity-mediated death in vitro, and systemic administration of DHF before moderate CCI injury reduced the death of adult-born immature neurons in the hippocampus 24 hours after injury. By contrast, inhibiting BDNF signaling using the TrkB antagonist ANA12 attenuated the neuroprotective effects of DHF. These data indicate that DHF may be a promising chemical compound that promotes immature neuron survival after TBI through activation of the BDNF signaling pathway.

Original languageEnglish (US)
Pages (from-to)557-567
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume74
Issue number6
DOIs
StatePublished - Jun 4 2015

Keywords

  • 7,8-dihydroxyflavone
  • Brain-derived neurotrophic factor
  • Cell death
  • Neuroprotection
  • Newborn neuron
  • Traumatic brain injury

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

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