Original Research ARTICLE
2-BFI provides neuroprotection against inflammation and necroptosis in a rat model of traumatic brain injury
- 1Zhangjiagang City First People's Hospital, China
- 2First Affiliated Hospital of Soochow University, China
Inflammation and programmed necrosis (necroptosis) are the 2 hallmark pathological changes after traumatic brain injury (TBI) that contribute to aggravated brain damage. 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) has been shown to exert both anti-inflammatory and programmed cell death effects. Therefore, the aim of the present study was to evaluate the potential beneficial effects of 2-BFI in a rat model of TBI induced by a weight-drop device. 2-BFI or vehicle was given via intraperitoneal injection starting at 30 min post trauma and then twice daily for three consecutive days. Following a neurofunctional test at 72 hours after injury, histological, molecular, and immunohistochemistry analyses were performed on the pericontusional areas of the brain. 2-BFI treatment significantly attenuated neurological deficits, brain edema and blood-brain barrier permeability after TBI. Also, treatment with 2-BFI significantly reduced microglial activation, neutrophil infiltration, and proinflammatory cytokine interleukin (IL)-1β secretion, which is related to nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation after TBI. In addition, 2-BFI treatment markedly reduced cortical tissue loss as well as repressed TBI-induced increases in necroptosis and necroptosis-associated proteins, including receptor-interacting protein (RIP1), RIP3, and mixed linkage kinase domain-like (MLKL) in the pericontusional brain tissue. Taken together, these findings indicate that 2-BFI may be an effective neuroprotectant after brain trauma and warrants further study.
Keywords: 2-BFI, Inflammation, necroptosis, Neuroprotection, Traumatic Brain Injury
Received: 25 Apr 2019;
Accepted: 12 Jun 2019.
Edited by:Luis F. Callado, University of the Basque Country, Spain
Reviewed by:Kevin D. Broad, Institute of Ophthalmology, Faculty of Brain Sciences, University College London, United Kingdom
M. Julia Garcia-Fuster, University of the Balearic Islands, Spain
Copyright: © 2019 Ni, Qui, Lin, Li, Liu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Huixiang Liu, Zhangjiagang City First People's Hospital, Zhangjiagang, China, firstname.lastname@example.org