期刊
BRAIN RESEARCH
卷 1698, 期 -, 页码 1-10出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2018.05.040
关键词
Subarachnoid haemorrhage; Dexmedetomidine; Anti-inflammation; Neuroprotection; NLRP3 inflammasome; TLR4/NF-kappa B pathway
资金
- National Natural Science Foundation of China [81330029, 81700403, 81671380]
- Tianjin Research Program of Application Foundation and Advanced Technology [15JCQNJC11300]
- Science & Technology Development Fund of Tianjin Education Commission for Higher Education [2016YD02]
- Natural Science Foundation of Tianjin City [17JCZDJC35900]
- Tianjin Research Program [16PTSYJC00180]
- Technology Program Fund of Tianjin Health and Family Planning Commission [2018001]
- National Key R&D Program of China [2017YFC1104004]
Early brain injury (EBI) plays a pivotal role in the prognosis of patients with subarachnoid haemorrhage (SAH). Dexmedetomidine (DEX), a highly selective alpha(2) receptor agonist, is reported to exert multiple protective effects in many neurological diseases. This study was designed to investigate whether DEX had neuroprotective functions in EBI after SAH, and to explore the possible mechanisms. The SAH model was established by an endovascular perforation in adult male Sprague-Dawley (SD) rats. DEX (25 mu g/kg) or vehicle was administered intraperitoneally 2 h after SAH. Neurological deficits, brain oedema, inflammation, BBB damage, and cell apoptosis at 24 h after SAH were evaluated. Additionally, the expression of components of the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-kappa B) pathway, and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome were also assessed. We demonstrated that DEX treatment improved neurological scores, alleviated brain oedema, reduced the permeability of the blood-brain barrier (BBB), and up-regulated the expression of tight junction proteins. DEX treatment could reduce the neutrophil infiltration, microglial activation, and pro-inflammatory factor release. In addition, DEX alleviated cell apoptosis at 24 h after SAH. Notably, DEX could also suppress the activation of the TLR4/NF-kappa B pathway and the NLRP3 inflammasome. These findings suggested that treatment with DEX after SAH attenuated SAH-induced EBI, partially through the suppression of the TLR4/NF-kappa B pathway and the NLRP3 inflammasome. (C) 2018 Published by Elsevier B.V.
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