Effects of early administration of insulin-like growth factor-1 on cognitive function in septic encephalopathy
Yang Yang,1,* Shengru Liang,2,* Yuqian Li,1,* Fei Gao,1 Yuan Cao,3 Xiaoyu Zhao,4 Guodong Gao,1 Lihong Li1 1Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi Province 710038, China; 2Department of Endocrinology, Xijing Hospital, Air Force Medical Uni...
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Dove Medical Press
2019
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oai:doaj.org-article:f8833658a68f49cd84c6f4eb0048e44b2021-12-02T00:09:45ZEffects of early administration of insulin-like growth factor-1 on cognitive function in septic encephalopathy1178-2021https://doaj.org/article/f8833658a68f49cd84c6f4eb0048e44b2019-01-01T00:00:00Zhttps://www.dovepress.com/effects-of-early-administration-of-insulin-like-growth-factor-1-on-cog-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Yang Yang,1,* Shengru Liang,2,* Yuqian Li,1,* Fei Gao,1 Yuan Cao,3 Xiaoyu Zhao,4 Guodong Gao,1 Lihong Li1 1Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi Province 710038, China; 2Department of Endocrinology, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi Province 710032, China; 3Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi Province 710032, China; 4Department of Neurosurgery, The 986th Hospital of Chinese People’s Libertation Army, Xi’an, Shaanxi Province 710054, China *These authors contributed equally to this work Background: Both protective and therapeutic functions of insulin-like growth factor-1 (IGF-1) in brain injury have been reported, but its effects on cognitive sequelae after septic encephalopathy (SE) remain unclear.Materials and methods: This study was divided into three parts, and a septic model was built by cecal ligation and puncture (CLP). First, survival analysis was performed, and IGF-1’s effects on long-term cognition and depressive emotion were assessed. Second, the characteristics of IGF-1 function in cognition were evaluated. Finally, cytochrome C, caspase-9, tumor necrosis factor receptor (TNFR), and caspase-8 levels as well as cell apoptosis in the hippocampus were evaluated.Results: IGF-1 did not reduce mortality or alleviate depressive symptoms in septic rats, but improved the memory of noxious stimulation and spatial learning and memory. These effects were observed only when IGF-1 was administered within 0–6 hours after CLP. Moreover, cytochrome C and caspase-9 expression levels were increased at 6 hours after CLP in the hippocampus, while TNFR and caspase-8 amounts were not increased until 12 hours after CLP. Cell apoptosis increased at 12 hours after CLP, but was inhibited by IGF-1.Conclusion: Cognitive impairment in rats recovering from SE is associated with cell apoptosis in the hippocampus. Supplementation of IGF-1 reduces cell apoptosis by preventing the over-expression of cytochrome C and TNFR, and results in improved cognitive function. However, improvement only occurs when IGF-1 is administered at the early stage (within 6 hours) of sepsis. As cytochrome C activation occurs earlier than that of TNFR in this study, cytochrome C may be the main factor inducing apoptosis in early SE. Keywords: septic encephalopy, memory, learning, IGF-1, cytochrome C, TNFR, apoptosisYang YLiang SLi YGao FCao YZhao XGao GLi LDove Medical PressarticleSEcognitive functionIGF-1Cytochrome CTNFRApoptosisNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 15, Pp 323-337 (2019) |
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SE cognitive function IGF-1 Cytochrome C TNFR Apoptosis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 |
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SE cognitive function IGF-1 Cytochrome C TNFR Apoptosis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Yang Y Liang S Li Y Gao F Cao Y Zhao X Gao G Li L Effects of early administration of insulin-like growth factor-1 on cognitive function in septic encephalopathy |
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Yang Yang,1,* Shengru Liang,2,* Yuqian Li,1,* Fei Gao,1 Yuan Cao,3 Xiaoyu Zhao,4 Guodong Gao,1 Lihong Li1 1Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi Province 710038, China; 2Department of Endocrinology, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi Province 710032, China; 3Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi Province 710032, China; 4Department of Neurosurgery, The 986th Hospital of Chinese People’s Libertation Army, Xi’an, Shaanxi Province 710054, China *These authors contributed equally to this work Background: Both protective and therapeutic functions of insulin-like growth factor-1 (IGF-1) in brain injury have been reported, but its effects on cognitive sequelae after septic encephalopathy (SE) remain unclear.Materials and methods: This study was divided into three parts, and a septic model was built by cecal ligation and puncture (CLP). First, survival analysis was performed, and IGF-1’s effects on long-term cognition and depressive emotion were assessed. Second, the characteristics of IGF-1 function in cognition were evaluated. Finally, cytochrome C, caspase-9, tumor necrosis factor receptor (TNFR), and caspase-8 levels as well as cell apoptosis in the hippocampus were evaluated.Results: IGF-1 did not reduce mortality or alleviate depressive symptoms in septic rats, but improved the memory of noxious stimulation and spatial learning and memory. These effects were observed only when IGF-1 was administered within 0–6 hours after CLP. Moreover, cytochrome C and caspase-9 expression levels were increased at 6 hours after CLP in the hippocampus, while TNFR and caspase-8 amounts were not increased until 12 hours after CLP. Cell apoptosis increased at 12 hours after CLP, but was inhibited by IGF-1.Conclusion: Cognitive impairment in rats recovering from SE is associated with cell apoptosis in the hippocampus. Supplementation of IGF-1 reduces cell apoptosis by preventing the over-expression of cytochrome C and TNFR, and results in improved cognitive function. However, improvement only occurs when IGF-1 is administered at the early stage (within 6 hours) of sepsis. As cytochrome C activation occurs earlier than that of TNFR in this study, cytochrome C may be the main factor inducing apoptosis in early SE. Keywords: septic encephalopy, memory, learning, IGF-1, cytochrome C, TNFR, apoptosis |
format |
article |
author |
Yang Y Liang S Li Y Gao F Cao Y Zhao X Gao G Li L |
author_facet |
Yang Y Liang S Li Y Gao F Cao Y Zhao X Gao G Li L |
author_sort |
Yang Y |
title |
Effects of early administration of insulin-like growth factor-1 on cognitive function in septic encephalopathy |
title_short |
Effects of early administration of insulin-like growth factor-1 on cognitive function in septic encephalopathy |
title_full |
Effects of early administration of insulin-like growth factor-1 on cognitive function in septic encephalopathy |
title_fullStr |
Effects of early administration of insulin-like growth factor-1 on cognitive function in septic encephalopathy |
title_full_unstemmed |
Effects of early administration of insulin-like growth factor-1 on cognitive function in septic encephalopathy |
title_sort |
effects of early administration of insulin-like growth factor-1 on cognitive function in septic encephalopathy |
publisher |
Dove Medical Press |
publishDate |
2019 |
url |
https://doaj.org/article/f8833658a68f49cd84c6f4eb0048e44b |
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