CPCGI Reduces Gray and White Matter Injury by Upregulating Nrf2 Signaling and Suppressing Calpain Overactivation in a Rat Model of Controlled Cortical Impact
Authors Niu F, Qian K, Qi H, Zhao Y, Jiang Y, Jia W, Sun M
Received 4 June 2020
Accepted for publication 28 July 2020
Published 12 August 2020 Volume 2020:16 Pages 1929—1941
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Yuping Ning
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 work
Correspondence: Ming Sun
Department 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 China
Tel/ Fax +86-10-59975497
Background: 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
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