1. Academic Validation
  2. Inhibition of myeloid differentiation primary response protein 88 provides neuroprotection in early brain injury following experimental subarachnoid hemorrhage

Inhibition of myeloid differentiation primary response protein 88 provides neuroprotection in early brain injury following experimental subarachnoid hemorrhage

  • Sci Rep. 2017 Nov 17;7(1):15797. doi: 10.1038/s41598-017-16124-8.
Huiying Yan 1 Dingding Zhang 1 Yongxiang Wei 1 Hongbin Ni 1 Weibang Liang 1 Huasheng Zhang 1 Shuangying Hao 2 Wei Jin 3 Kuanyu Li 4 Chun-Hua Hang 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhongshan Road 321, Nanjing, 210008, China.
  • 2 Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, 22 Hankou Road, Nanjing, 210093, China.
  • 3 Department of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhongshan Road 321, Nanjing, 210008, China. [email protected].
  • 4 Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, 22 Hankou Road, Nanjing, 210093, China. [email protected].
  • 5 Department of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhongshan Road 321, Nanjing, 210008, China. [email protected].
Abstract

Accumulating of evidence suggests that activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) exacerbates early brain injury (EBI) following subarachnoid hemorrhage (SAH) by provoking pro-inflammatory and pro-apoptotic signaling. Myeloid differentiation primary response protein 88 (MyD88) is an endogenous adaptor protein in the toll-like receptors (TLRs) and interleukin (IL) -1β family signaling pathways and acts as a bottle neck in the NF-κB and MAPK pathways. Here, we used ST2825, a selective inhibitor of MyD88, to clarify whether inhibiting MyD88 could provide neuroprotection in EBI following SAH. Our results showed that the expression of MyD88 was markedly increased at 24 h post SAH. Intracerebroventricular injection of ST2825 significantly reduced the expression of MyD88 at 24 h post SAH. Involvement of MAPKs and NF-κB signaling pathways was revealed that ST2825 inhibited SAH-induced phosphorylation of TAK1, p38 and JNK, the nuclear translocation of NF-κB p65, and degradation of IκBα. Further, ST2825 administration diminished the SAH-induced inflammatory response and Apoptosis. As a result, SAH-induced EBI was alleviated and neurological deficits caused by SAH were reversed. Our findings suggest that MyD88 inhibition confers marked neuroprotection against EBI following SAH. Therefore, MyD88 might be a promising new molecular target for the treatment of SAH.

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