bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration
Abstract Introduction Neonatal hypoxia–ischemic brain damage (HIBD) can lead to serious neuron damage and dysfunction, causing a significant worldwide health problem. bFGF as a protective reagent promotes neuron repair under hypoxia/ischemia (HI). However, how bFGF and downstream molecules were regu...
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doaj-910a038128b84515b57fa4a188af95792020-11-25T03:53:14ZengWileyBrain and Behavior2162-32792020-08-01108n/an/a10.1002/brb3.1696bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regenerationZheng Ma0Fang Wang1Lu‐Lu Xue2Ying‐Jie Niu3Yue Hu4Zhang‐Yu Su5Jin Huang6Rui‐Ze Niu7Ting‐Hua Wang8Ying‐Chun Ba9Liu‐Lin Xiong10Xue Bai11Department of Anatomy Kunming Medical University Kunming ChinaInstitute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming ChinaInstitute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming ChinaInstitute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming ChinaInstitute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming ChinaNational Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou ChinaInstitute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming ChinaInstitute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming ChinaInstitute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming ChinaDepartment of Anatomy Kunming Medical University Kunming ChinaNational Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou ChinaNational Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou ChinaAbstract Introduction Neonatal hypoxia–ischemic brain damage (HIBD) can lead to serious neuron damage and dysfunction, causing a significant worldwide health problem. bFGF as a protective reagent promotes neuron repair under hypoxia/ischemia (HI). However, how bFGF and downstream molecules were regulated in HI remains elusive. Methods We established an in vitro HI model by culturing primary cortical neurons and treated with oxygen–glucose deprivation (OGD). We suppressed the expression of bFGF by using siRNA (small interfering RNA) interference to detect the neuronal morphological changes by immunofluorescence staining. To determine the potential mechanisms regulated by bFGF, the change of downstream molecular including IL‐1β was examined in bFGF knockdown condition. IL‐1β knockout (KO) rats were generated using CRISPR/Cas9‐mediated technologies. We used an accepted rat model of HI, to assess the effect of IL‐1β deletion on disease outcomes and carried out analysis on the behavior, histological, cellular, and molecular level. Results We identified that OGD can induce endogenous expression of bFGF. Both OGD and knockdown of bFGF resulted in reduction of neuron numbers, enlarged cell body and shortened axon length. We found molecules closely related to bFGF, such as interleukin‐1β (IL‐1β). IL‐1β was up‐regulated after bFGF interference under OGD conditions, suggesting complex signaling between bFGF and OGD‐mediated pathways. We found HI resulted in up‐regulation of IL‐1β mRNA in cortex and hippocampus. IL‐1β KO rats markedly attenuated the impairment of long‐term learning and memory induced by HI. Meanwhile, IL‐1β−/− (KO, homozygous) group showed better neurite growth and less apoptosis in OGD model. Furthermore, serine/threonine protein kinase (AKT1) mRNA and protein expression was significantly up‐regulated in IL‐1β KO rats. Conclusions We showed that IL‐1β‐mediated axon regeneration underlie the mechanism of bFGF for the treatment of HIBD in neonatal rats. Results from this study would provide insights and molecular basis for future therapeutics in treating HIBD.https://doi.org/10.1002/brb3.1696bFGF‐siRNAIL‐1β knockoutneonatal hypoxic–ischemic brain damageneurological recoveryoxygen–glucose deprivation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zheng Ma Fang Wang Lu‐Lu Xue Ying‐Jie Niu Yue Hu Zhang‐Yu Su Jin Huang Rui‐Ze Niu Ting‐Hua Wang Ying‐Chun Ba Liu‐Lin Xiong Xue Bai |
spellingShingle |
Zheng Ma Fang Wang Lu‐Lu Xue Ying‐Jie Niu Yue Hu Zhang‐Yu Su Jin Huang Rui‐Ze Niu Ting‐Hua Wang Ying‐Chun Ba Liu‐Lin Xiong Xue Bai bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration Brain and Behavior bFGF‐siRNA IL‐1β knockout neonatal hypoxic–ischemic brain damage neurological recovery oxygen–glucose deprivation |
author_facet |
Zheng Ma Fang Wang Lu‐Lu Xue Ying‐Jie Niu Yue Hu Zhang‐Yu Su Jin Huang Rui‐Ze Niu Ting‐Hua Wang Ying‐Chun Ba Liu‐Lin Xiong Xue Bai |
author_sort |
Zheng Ma |
title |
bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration |
title_short |
bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration |
title_full |
bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration |
title_fullStr |
bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration |
title_full_unstemmed |
bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration |
title_sort |
bfgf promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by il‐1β signaling pathway‐mediated axon regeneration |
publisher |
Wiley |
series |
Brain and Behavior |
issn |
2162-3279 |
publishDate |
2020-08-01 |
description |
Abstract Introduction Neonatal hypoxia–ischemic brain damage (HIBD) can lead to serious neuron damage and dysfunction, causing a significant worldwide health problem. bFGF as a protective reagent promotes neuron repair under hypoxia/ischemia (HI). However, how bFGF and downstream molecules were regulated in HI remains elusive. Methods We established an in vitro HI model by culturing primary cortical neurons and treated with oxygen–glucose deprivation (OGD). We suppressed the expression of bFGF by using siRNA (small interfering RNA) interference to detect the neuronal morphological changes by immunofluorescence staining. To determine the potential mechanisms regulated by bFGF, the change of downstream molecular including IL‐1β was examined in bFGF knockdown condition. IL‐1β knockout (KO) rats were generated using CRISPR/Cas9‐mediated technologies. We used an accepted rat model of HI, to assess the effect of IL‐1β deletion on disease outcomes and carried out analysis on the behavior, histological, cellular, and molecular level. Results We identified that OGD can induce endogenous expression of bFGF. Both OGD and knockdown of bFGF resulted in reduction of neuron numbers, enlarged cell body and shortened axon length. We found molecules closely related to bFGF, such as interleukin‐1β (IL‐1β). IL‐1β was up‐regulated after bFGF interference under OGD conditions, suggesting complex signaling between bFGF and OGD‐mediated pathways. We found HI resulted in up‐regulation of IL‐1β mRNA in cortex and hippocampus. IL‐1β KO rats markedly attenuated the impairment of long‐term learning and memory induced by HI. Meanwhile, IL‐1β−/− (KO, homozygous) group showed better neurite growth and less apoptosis in OGD model. Furthermore, serine/threonine protein kinase (AKT1) mRNA and protein expression was significantly up‐regulated in IL‐1β KO rats. Conclusions We showed that IL‐1β‐mediated axon regeneration underlie the mechanism of bFGF for the treatment of HIBD in neonatal rats. Results from this study would provide insights and molecular basis for future therapeutics in treating HIBD. |
topic |
bFGF‐siRNA IL‐1β knockout neonatal hypoxic–ischemic brain damage neurological recovery oxygen–glucose deprivation |
url |
https://doi.org/10.1002/brb3.1696 |
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