Transplantation of Human Umbilical Cord Blood Mononuclear Cells Attenuated Ischemic Injury in MCAO Rats via Inhibition of NF-κB and NLRP3 Inflammasome. (15th January 2018)

• Record Type: Journal Article
• Authors: Liu, Lu; Cen, Juan; Man, Yong; Li, Jianbin; Zhang, Dahuan; Wang, Fei; Li, Jinhua; Ma, Ji; Wang, Xiaoming; Ji, Biansheng
• Is Part Of: Neuroscience. Volume 369(2018)
• Page Start: 314
• Page End: 324
• Publication Date: 2018-01-15
• Subjects: Ang-1 angiopoietin-1 -- BrdU bromodeoxyuridine -- CAT catalase -- cbMNCs cord blood mononuclear cells -- GSH glutathion -- HUCB human umbilical cord blood -- ICA internal carotid artery -- IHC immunohistochemistry -- IL-1β interleukin-1β -- LCBF local cerebral blood flow -- LDF laser-Doppler fluxmetry -- MCAO middle cerebral artery occlusion -- mNSS modified neurologic severity score -- NF-κB nuclear factor-κB -- PBS phosphate-buffered saline solution -- ROS reactive oxygen species -- SOD superoxide dismutase -- Tie-2 tyrosine kinase 2 -- tPA tissue plasminogen activator -- VEGF vascular endothelial growth factor; human umbilical cord blood mononuclear cells -- Transplantation -- middle cerebral artery occlusion; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.11.027
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: cbMNCs reduced cerebral infarct volume and cell apoptosis in the brain of the MCAO rats. cbMNCs improved neurologic deficits, learning and memory function. cbMNCs enhanced angiogenesis, VEGF release and Ang-1/Tie-2 signaling pathway. cbMNCs inhibited NF-κB pathway and NLRP3 inflammasome. Abstract: Accumulated evidence displayed that transplantation of stem cells may be a promising approach for the treatment of neurological disorders. However, the underlying mechanisms remain to be well elucidated. Moreover, some investigators cannot reproduce similar results as the previous. The present results showed that transplantation of fresh human umbilical cord blood mononuclear cells (cbMNCs) attenuated ischemic damage in middle cerebral artery occlusion (MCAO) rats, accompanied with improvement of neurologic deficits, learning and memory function. The increase in neovascularization and related molecules such as vascular endothelial growth factor (VEGF), Angiopoietin-1 (Ang-1) and endothelium-specific receptor tyrosine kinase 2 (Tie-2) in the injured brain was observed in cbMNCs-treated rats. Moreover, nuclear factor-κB (NF-κB) activation and nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome were also inhibited by the cells graft, resulting in reduction in cleaved caspase-1 and mature interleukin-1β (IL-1β) content. These results suggested that the protective actions of the cells on the cerebral ischemia may be related to inhibition of NF-κB pathway and NLRP3 inflammasome.