2. Academic Validation
  3. Inhibition of myeloid differentiation factor 88(MyD88) by ST2825 provides neuroprotection after experimental traumatic brain injury in mice

Inhibition of myeloid differentiation factor 88(MyD88) by ST2825 provides neuroprotection after experimental traumatic brain injury in mice

  • Brain Res. 2016 Jul 15;1643:130-9. doi: 10.1016/j.brainres.2016.05.003.
Hua-Sheng Zhang 1,  Hua Li 2,  Ding-Ding Zhang 1,  Hui-Ying Yan 1,  Zi-Huan Zhang 3,  Chen-Hui Zhou 1,  Zhen-Nan Ye 4,  Qiang Chen 4,  Tian-Wei Jiang 1,  Jing-Peng Liu 4,  Chun-Hua Hang 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, PR China.
  • 2 Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, PR China.
  • 3 Department of Neurosurgery, Zhongdu Hospital, Bengbu, Anhui Province, PR China.
  • 4 Department of Neurosurgery, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, PR China.
  • 5 Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, PR China; Department of Neurosurgery, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, PR China. Electronic address: hang_neurosurgery@163.com.
PMID: 27155455 DOI: 10.1016/j.brainres.2016.05.003
Abstract

Myeloid differentiation factor 88(MyD88) is an endogenous adaptor protein that plays an important role in coordinating intracellular inflammatory responses induced by agonists of the Toll-like Receptor and interleukin-1 receptor families. MyD88 has been reported to be essential for neuronal death in animal models and may represent a therapeutic target for pharmacologic inhibition following traumatic brain injury (TBI). The purpose of the current study was to investigate the neuroprotective effect of MyD88 specific inhibitor ST2825 in an experimental mouse model of TBI. Intracerebroventricular (ICV) injection of high concentration (20μg/μL) ST2825 (15min post TBI) attenuated the development of TBI in mice, markedly improved neurological function and reduced brain edema. Decreased neural Apoptosis and increased neuronal survival were also observed. Biochemically, the high concentration of ST2825 significantly reduced the levels of MyD88, further decreased TAK1, p-TAK1, nuclear p65 and increased IκB-α. Additionally, ST2825 significantly reduced the levels of Iba-1 and inflammatory factors TNF-α and IL-1β. These data provide an experimental rationale for evaluation of MyD88 as a drug target and highlight the potential therapeutic implications of ST2825 in TBI.

Keywords

Apoptosis; Myeloid differentiation factor 88; ST2825; Traumatic brain injury.

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