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Author Notes:

Corresponding author: Shan Ping Yu, MD/PhD, 101 Woodruff circle, Emory University School of Medicine, Atlanta, GA 30322; Ling Wei, M.D., 101 Woodruff Circle, Woodruff Memorial Research Building, Suite 617, Emory University School of Medicine, Atlanta, GA 30322, lwei7@emory.edu, Tel. 404-712-8221; Fax: 404-727-6300.

NBP was a gift from Shijiazhuang Pharmaceutical Group Ouyi Pharma Co., Ltd, (Shijiazhuang, China). No competing financial interests exist.

Subjects:

Research Funding:

This study was supported by NS075338 (LW), NS085568 (LW/SPY), NS091585 (LW), AHA Postdoctoral Fellowship 15POST25680013 (JHL), and a VA Merit grant RX000666 (SPY).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Neurosciences
  • Neurosciences & Neurology
  • NBP
  • Traumatic brain injury
  • Regeneration
  • Inflammation
  • Depression
  • FOCAL CEREBRAL-ISCHEMIA
  • PHARMACOLOGICALLY INDUCED HYPOTHERMIA
  • ADULT-RAT HIPPOCAMPUS
  • NEURAL STEM
  • CHIRAL 3-N-BUTYLPHTHALIDE
  • PARKINSONS-DISEASE
  • PROGENITOR CELLS
  • DENTATE GYRUS
  • NITRIC-OXIDE
  • HEAD-INJURY

DL-3-n-butylphthalide induced neuroprotection, regenerative repair, functional recovery and psychological benefits following traumatic brain injury in mice

Tools:

Journal Title:

Neurochemistry International

Volume:

Volume 111

Publisher:

, Pages 82-92

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Previous investigations suggest that DL-3-n-butylphthalide (NBP) is a promising multifaceted drug for the treatment of stroke. It is not clear whether NBP can treat traumatic brain injury (TBI) and what could be the mechanisms of therapeutic benefits. To address these issues, TBI was induced by a controlled cortical impact in adult male mice. NBP (100 mg/kg) or saline was intraperitoneally administered within 5 min after TBI. One day after TBI, apoptotic events including caspase-3/9 activation, cytochrome c release from the mitochondria, and apoptosis-inducing factor (AIF) translocation into the nucleus in the pericontusion region were attenuated in NBP-treated mice compared to TBI-saline controls. In the assessment of the nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway, NBP ameliorated the p65 expression and the p-IκB-α/IκB-α ratio, indicating reduced NF-κB activation. Consistently, NBP reduced the upregulation of proinflammatory cytokines such as tumor necrotizing factor-alpha (TNF-α) and interleukin-1beta (IL-1β) after TBI. In sub-acute treatment experiments, NBP was intranasally delivered once daily for 3 days. At 3 days after TBI, this repeated NBP treatment significantly reduced the contusion volume and cell death in the pericontusion region. In chronic experiments up to 21 days after TBI, continues daily intranasal NBP treatment increased neurogenesis, angiogenesis, and arteriogenesis in the post-TBI brain, accompanied with upregulations of regenerative genes including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), endothelial-derived nitric oxide synthase (eNOS), and matrix metallopeptidase 9 (MMP-9). The NBP treatment significantly improved sensorimotor functional recovery and reduced post-TBP depressive behavior. These new findings demonstrate that NBP shows multiple therapeutic benefits after TBI.

Copyright information:

© 2017 Elsevier Ltd

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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