Journal Home > Volume 8 , Issue 2
Journal of Neurorestoratology 2020, 8(2): 122-130 https://doi.org/10.26599/JNR.2020.9040015
Research Article | Open Access | Issue | Published: 04 August 2020

Transplantation of umbilical cord blood mononuclear cells attenuates the expression of IL-1β via the TLR4/NF-κB pathway in hypoxic-ischemic neonatal rats

Show Author's Information Meng-Bei Zhang1,  Chao-Chao Song2,  Guang-Zu Li1,  Lan-Fen Chen1,  Rui Ma1,  Xiao-He Yu3,  Ping Gong1,  Xiao-Li Wang1( )
Department of Medical Imaging, Weifang Medical University, Weifang 261053, Shandong, China
Department of Digestive System, People’s Hospital of Fangzi District, Weifang 261200, Shandong, China
Department of Pediatrics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
Keywords:
umbilical cord blood mononuclear cell (UCBMC), hypoxic ischemic brain damage (HIBD), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), TLR4/NF-κB pathway, neonatal rats
Cite this article:
Zhang M-B, Song C-C, Li G-Z, et al. Transplantation of umbilical cord blood mononuclear cells attenuates the expression of IL-1β via the TLR4/NF-κB pathway in hypoxic-ischemic neonatal rats. Journal of Neurorestoratology, 2020, 8(2): 122-130. https://doi.org/10.26599/JNR.2020.9040015
Download citation
EndNote(RIS)
BibTeX

689

Views

40

Downloads

Citations

12

Crossref

10

WoS

0

Scopus

N/A

CSCD

Abstract Full text About this article
Objective:

This study aims to observe the effects of transplantation of umbilical cord blood mononuclear cells (UCBMCs) on the expression of interleukin (IL)-1β and explore the mechanism via the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway in hypoxic-ischemic neonatal rats.

Methods:

Seven-day-old Sprague-Dawley neonatal rats were randomly divided into Sham, hypoxic-ischemic brain damage (HIBD), and UCBMC groups. The HIBD model was prepared by Rice-Vannucci method, and UCBMC were transplanted 24 h after HIBD in the UCBMC group. At 7 days after transplantation, changes in neurons and the TLR4 protein were examined by neuronal nuclei (NeuN)/TLR4 immunofluorescence staining. The expression of pNF-κB and IL-1β proteins was detected by immunohistochemical staining and enzyme linked immunosorbent assay (ELISA).

Results:

The percentage of NeuN+DAPI+ cells in the injured cortex in the UCBMC group was significantly higher than that in the HIBD group and lower than that in the Sham group (P < 0.05). The number of NeuN+TLR4+DAPI+cells in the UCBMC group was significantly lower than that in the HIBD group (P < 0.05) but higher than that in the Sham group (P < 0.05). More pNF-κB+ cells were observed in the HIBD group than in Sham and UCBMC groups (P < 0.05), and more pNF-κB+ cells were observed in the UCBMC group than in the Sham group (P < 0.05). ELISA results showed that the IL-1β expression in the injured cerebral cortex in the UCMBC group was significantly lower than that in the HIBD group but remained higher than that in the Sham group (P < 0.05).

Conclusions:

UCBMC transplantation could inhibit the IL-1β protein expression in the injured cortex, thereby alleviating HIBD in neonatal rats. The underlying mechanism might be associated with the down- regulation of TLR4 and pNF-κB proteins.


menu
Abstract
Full text
Outline
About this article

Transplantation of umbilical cord blood mononuclear cells attenuates the expression of IL-1β via the TLR4/NF-κB pathway in hypoxic-ischemic neonatal rats

Show Author's information Meng-Bei Zhang1, Chao-Chao Song2, Guang-Zu Li1, Lan-Fen Chen1, Rui Ma1, Xiao-He Yu3, Ping Gong1, Xiao-Li Wang1( )
Department of Medical Imaging, Weifang Medical University, Weifang 261053, Shandong, China
Department of Digestive System, People’s Hospital of Fangzi District, Weifang 261200, Shandong, China
Department of Pediatrics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China

Abstract

Objective:

This study aims to observe the effects of transplantation of umbilical cord blood mononuclear cells (UCBMCs) on the expression of interleukin (IL)-1β and explore the mechanism via the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway in hypoxic-ischemic neonatal rats.

Methods:

Seven-day-old Sprague-Dawley neonatal rats were randomly divided into Sham, hypoxic-ischemic brain damage (HIBD), and UCBMC groups. The HIBD model was prepared by Rice-Vannucci method, and UCBMC were transplanted 24 h after HIBD in the UCBMC group. At 7 days after transplantation, changes in neurons and the TLR4 protein were examined by neuronal nuclei (NeuN)/TLR4 immunofluorescence staining. The expression of pNF-κB and IL-1β proteins was detected by immunohistochemical staining and enzyme linked immunosorbent assay (ELISA).

Results:

The percentage of NeuN+DAPI+ cells in the injured cortex in the UCBMC group was significantly higher than that in the HIBD group and lower than that in the Sham group (P < 0.05). The number of NeuN+TLR4+DAPI+cells in the UCBMC group was significantly lower than that in the HIBD group (P < 0.05) but higher than that in the Sham group (P < 0.05). More pNF-κB+ cells were observed in the HIBD group than in Sham and UCBMC groups (P < 0.05), and more pNF-κB+ cells were observed in the UCBMC group than in the Sham group (P < 0.05). ELISA results showed that the IL-1β expression in the injured cerebral cortex in the UCMBC group was significantly lower than that in the HIBD group but remained higher than that in the Sham group (P < 0.05).

Conclusions:

UCBMC transplantation could inhibit the IL-1β protein expression in the injured cortex, thereby alleviating HIBD in neonatal rats. The underlying mechanism might be associated with the down- regulation of TLR4 and pNF-κB proteins.

Keywords: umbilical cord blood mononuclear cell (UCBMC), hypoxic ischemic brain damage (HIBD), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), TLR4/NF-κB pathway, neonatal rats

References(13)

[1]
SK Yum, CJ Moon, YA Youn, et al. Changes in lactate dehydrogenase are associated with central gray matter lesions in newborns with hypoxic- ischemic encephalopathy. J Matern Fetal Neonatal Med. 2017, 30(10): 1177-1181.
DOI Google Scholar
[2]
MK Mwaniki, M Atieno, JE Lawn, et al. Long-term neurodevelopmental outcomes after intrauterine and neonatal insults: a systematic review. Lancet. 2012, 379(9814): 445-452.
DOI Google Scholar
[3]
LR Shiow, G Favrais, L Schirmer, et al. Reactive astrocyte COX2-PGE2 production inhibits oligodendrocyte maturation in neonatal white matter injury. Glia. 2017, 65(12): 2024-2037.
DOI Google Scholar
[4]
C Grasselli, D Ferrari, C Zalfa, et al. Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation. Cell Death Dis. 2018, 9(3): 280.
DOI Google Scholar
[5]
EV Jones, DS Bouvier. Astrocyte-secreted matricellular proteins in CNS remodelling during development and disease. Neural Plast. 2014, 2014: 321209.
DOI Google Scholar
[6]
YZ Ye, T Jin, X Zhang, et al. Meisoindigo protects against focal cerebral ischemia-reperfusion injury by inhibiting NLRP3 inflammasome activation and regulating microglia/macrophage polarization via TLR4/NF-κB signaling pathway. Front Cell Neurosci. 2019, 13: 553.
DOI Google Scholar
[7]
YS Zhao, HY Wang, W Chen, et al. Melatonin attenuates white matter damage after focal brain ischemia in rats by regulating the TLR4/NF-κB pathway. Brain Res Bull. 2019, 150: 168-178.
DOI Google Scholar
[8]
MCB Paton, BJ Allison, MC Fahey, et al. Umbilical cord blood versus mesenchymal stem cells for inflammation-induced preterm brain injury in fetal sheep. Pediatr Res. 2019, 86(2): 165-173.
DOI Google Scholar
[9]
XL Wang, YS Zhao, X Wang. Umbilical cord blood cells regulate the differentiation of endogenous neural stem cells in hypoxic ischemic neonatal rats via the hedgehog signaling pathway. Brain Res. 2014, 1560: 18-26.
DOI Google Scholar
[10]
JE 3rd Rice, RC Vannucci, JB Brierley. The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol. 1981, 9(2): 131-141.
DOI Google Scholar
[11]
X Wang, XL Yang, WL Kong, et al. TRPV1 translocated to astrocytic membrane to promote migration and inflammatory infiltration thus promotes epilepsy after hypoxic ischemia in immature brain. J Neuroinflammation. 2019, 16(1): 214.
DOI Google Scholar
[12]
LJ Jiang, ZX Xu, MF Wu, et al. Resatorvid protects against hypoxic-ischemic brain damage in neonatal rats. Neural Regen Res. 2020, 15(7): 1316-1325.
DOI Google Scholar
[13]
W Zhang, JK Song, W Li, et al. Salvianolic acid D alleviates cerebral ischemia-reperfusion injury by suppressing the cytoplasmic translocation and release of HMGB1-triggered NF-κB activation to inhibit inflammatory response. Mediators Inflamm. 2020, 2020: 9049614.
DOI Google Scholar
Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Received: 21 May 2020
Revised: 11 June 2020
Accepted: 15 June 2020
Published: 04 August 2020
Issue date: June 2020

Copyright

© The authors 2020

Acknowledgements

The work was supported by the National Natural Science Foundation of China (Grant No. 81000268), and the Natural Science Foundation of Shandong Province (Grant No. ZR2014JL049).

Rights and permissions

This article is published with open access at http://jnr.tsinghuajournals.com

Return