CPCGI Reduces Gray and White Matter Injury by Upregulating Nrf2 Signaling and Suppressing Calpain Overactivation in a Rat Model of Controlled Cortical Impact

Fei Niu,1,* Ke Qian,2,* Hongyan Qi,3 Yumei Zhao,4 Yingying Jiang,4 Wang Jia,2 Ming Sun4 1Department of Neurotrauma, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, People’s Republic of China; 2Department...

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Autores principales:	Niu F, Qian K, Qi H, Zhao Y, Jiang Y, Jia W, Sun M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	compound porcine cerebroside and ganglioside injection traumatic brain injury nrf2 signaling oxidative stress calpain Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/b68d19987ad84155a322cfd3b16dc92c
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spelling	oai:doaj.org-article:b68d19987ad84155a322cfd3b16dc92c2021-12-02T12:59:52ZCPCGI Reduces Gray and White Matter Injury by Upregulating Nrf2 Signaling and Suppressing Calpain Overactivation in a Rat Model of Controlled Cortical Impact1178-2021https://doaj.org/article/b68d19987ad84155a322cfd3b16dc92c2020-08-01T00:00:00Zhttps://www.dovepress.com/cpcgi-reduces-gray-and-white-matter-injury-by-upregulating-nrf2-signal-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Fei Niu,1,* Ke Qian,2,* Hongyan Qi,3 Yumei Zhao,4 Yingying Jiang,4 Wang Jia,2 Ming Sun4 1Department of Neurotrauma, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, People’s Republic of China; 2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, People’s Republic of China; 3Department of Acupuncture, Lianyungang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Lianyungang City 222000, Jiangsu Province, People’s Republic of China; 4Department of Neuropharmacology, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming SunDepartment of Neuropharmacology, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, 119 South Fourth Ring West Road, Fengtai District, Beijing 100070, People’s Republic of ChinaTel/ Fax +86-10-59975497Email sunming999@yahoo.comBackground: Compound porcine cerebroside and ganglioside injection (CPCGI), which involves injection of a neurotrophic drug, has been widely used to treat certain brain disorders in the clinic; however, the detailed mechanism is unknown. This study investigated whether CPCGI protects the brain from trauma by stimulating antioxidative nuclear factor erythroid-2-related factor 2 (Nrf2) signaling and suppressing calpain overactivation in a rat model of controlled cortical impact (CCI).Materials and Methods: The rat model of CCI was used. Neurological deficits, contusion, and white matter damage were evaluated 3 days after CCI. Calpain activation, Nrf2 signaling and oxidative stress were determined 24 h after CCI.Results: CPCGI dose-dependently reduced neurological deficits, attenuated axonal and myelin sheath injury, and decreased contusion volume 3 days post-CCI. Moreover, CPCGI reduced calpain activity, and enhanced the cytosolic levels of calpastatin, αII-spectrin, microtubule-associated protein 2 (MAP2), neurofilament heavy chain (NF-H) and myelin basic protein (MBP) in traumatic tissues 24 h post-CCI. Furthermore, CPCGI reduced the levels of nuclear Kelch-like ECH-associated protein 1 (Keap1) and thioredoxin interacting protein (TXNIP); increased the levels of cytosolic Nrf2 and thioredoxin 1 (Trx 1) and nuclear Nrf2; increased the cytosolic and nuclear Nrf2/Keap1 and Trx 1/TXNIP ratios; enhanced the levels of heme oxygenase 1 (HO-1), glutathione (GSH), superoxide dismutase activity, and total antioxidative capacity; and reduced the levels of malondialdehyde in TBI tissues.Conclusion: These data confirm the neuroprotective effect of CPCGI against gray and white matter damage due to CCI and suggest that activating Nrf2 signaling and alleviating oxidative stress-mediated calpain activation could be one mechanism by which CPCGI protects against brain trauma.Keywords: compound porcine cerebroside and ganglioside injection, traumatic brain injury, Nrf2 signaling, oxidative stress, calpainNiu FQian KQi HZhao YJiang YJia WSun MDove Medical Pressarticlecompound porcine cerebroside and ganglioside injectiontraumatic brain injurynrf2 signalingoxidative stresscalpainNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 16, Pp 1929-1941 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	compound porcine cerebroside and ganglioside injection traumatic brain injury nrf2 signaling oxidative stress calpain Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	compound porcine cerebroside and ganglioside injection traumatic brain injury nrf2 signaling oxidative stress calpain Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Niu F Qian K Qi H Zhao Y Jiang Y Jia W Sun M CPCGI Reduces Gray and White Matter Injury by Upregulating Nrf2 Signaling and Suppressing Calpain Overactivation in a Rat Model of Controlled Cortical Impact
description	Fei Niu,1,* Ke Qian,2,* Hongyan Qi,3 Yumei Zhao,4 Yingying Jiang,4 Wang Jia,2 Ming Sun4 1Department of Neurotrauma, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, People’s Republic of China; 2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, People’s Republic of China; 3Department of Acupuncture, Lianyungang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Lianyungang City 222000, Jiangsu Province, People’s Republic of China; 4Department of Neuropharmacology, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming SunDepartment of Neuropharmacology, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, 119 South Fourth Ring West Road, Fengtai District, Beijing 100070, People’s Republic of ChinaTel/ Fax +86-10-59975497Email sunming999@yahoo.comBackground: Compound porcine cerebroside and ganglioside injection (CPCGI), which involves injection of a neurotrophic drug, has been widely used to treat certain brain disorders in the clinic; however, the detailed mechanism is unknown. This study investigated whether CPCGI protects the brain from trauma by stimulating antioxidative nuclear factor erythroid-2-related factor 2 (Nrf2) signaling and suppressing calpain overactivation in a rat model of controlled cortical impact (CCI).Materials and Methods: The rat model of CCI was used. Neurological deficits, contusion, and white matter damage were evaluated 3 days after CCI. Calpain activation, Nrf2 signaling and oxidative stress were determined 24 h after CCI.Results: CPCGI dose-dependently reduced neurological deficits, attenuated axonal and myelin sheath injury, and decreased contusion volume 3 days post-CCI. Moreover, CPCGI reduced calpain activity, and enhanced the cytosolic levels of calpastatin, αII-spectrin, microtubule-associated protein 2 (MAP2), neurofilament heavy chain (NF-H) and myelin basic protein (MBP) in traumatic tissues 24 h post-CCI. Furthermore, CPCGI reduced the levels of nuclear Kelch-like ECH-associated protein 1 (Keap1) and thioredoxin interacting protein (TXNIP); increased the levels of cytosolic Nrf2 and thioredoxin 1 (Trx 1) and nuclear Nrf2; increased the cytosolic and nuclear Nrf2/Keap1 and Trx 1/TXNIP ratios; enhanced the levels of heme oxygenase 1 (HO-1), glutathione (GSH), superoxide dismutase activity, and total antioxidative capacity; and reduced the levels of malondialdehyde in TBI tissues.Conclusion: These data confirm the neuroprotective effect of CPCGI against gray and white matter damage due to CCI and suggest that activating Nrf2 signaling and alleviating oxidative stress-mediated calpain activation could be one mechanism by which CPCGI protects against brain trauma.Keywords: compound porcine cerebroside and ganglioside injection, traumatic brain injury, Nrf2 signaling, oxidative stress, calpain
format	article
author	Niu F Qian K Qi H Zhao Y Jiang Y Jia W Sun M
author_facet	Niu F Qian K Qi H Zhao Y Jiang Y Jia W Sun M
author_sort	Niu F
title	CPCGI Reduces Gray and White Matter Injury by Upregulating Nrf2 Signaling and Suppressing Calpain Overactivation in a Rat Model of Controlled Cortical Impact
title_short	CPCGI Reduces Gray and White Matter Injury by Upregulating Nrf2 Signaling and Suppressing Calpain Overactivation in a Rat Model of Controlled Cortical Impact
title_full	CPCGI Reduces Gray and White Matter Injury by Upregulating Nrf2 Signaling and Suppressing Calpain Overactivation in a Rat Model of Controlled Cortical Impact
title_fullStr	CPCGI Reduces Gray and White Matter Injury by Upregulating Nrf2 Signaling and Suppressing Calpain Overactivation in a Rat Model of Controlled Cortical Impact
title_full_unstemmed	CPCGI Reduces Gray and White Matter Injury by Upregulating Nrf2 Signaling and Suppressing Calpain Overactivation in a Rat Model of Controlled Cortical Impact
title_sort	cpcgi reduces gray and white matter injury by upregulating nrf2 signaling and suppressing calpain overactivation in a rat model of controlled cortical impact
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/b68d19987ad84155a322cfd3b16dc92c
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CPCGI Reduces Gray and White Matter Injury by Upregulating Nrf2 Signaling and Suppressing Calpain Overactivation in a Rat Model of Controlled Cortical Impact

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