Tetrahydrocurcumin provides neuroprotection in rats after traumatic brain injury: Autophagy and the PI3K/AKT pathways as a potential mechanism

• Published in: The Journal of surgical research Vol. 206; no. 1; pp. 67 - 76
• Main Authors: Gao, Yongyue, MD, Li, Jie, MD, PhD, Wu, Lingyun, MD, PhD, Zhou, Chenhui, MD, PhD, Wang, Qiang, MD, PhD, Li, Xiang, MD, Zhou, Mengliang, MD, PhD, Wang, Handong, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2016
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Biomarkers - metabolism; Blotting, Western; Brain Injuries, Traumatic - drug therapy; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - physiopathology; Curcumin - analogs & derivatives; Curcumin - pharmacology; Curcumin - therapeutic use; Fluorescent Antibody Technique; In Situ Nick-End Labeling; Male; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Phosphatidylinositol 3-Kinases - metabolism; PI3K/AKT signaling pathway; Proto-Oncogene Proteins c-akt - metabolism; Random Allocation; Rats; Rats, Sprague-Dawley; Surgery; Tetrahydrocurcumin; Traumatic brain injury; Treatment Outcome; autophagy; phosphatidylinositide 3-kinases; traumatic brain injury; apoptosis; terminal deoxynucleotidyl transferase dUTP nick end-labeling; p-AKT; TUNEL; phospho-protein kinase B; PI3K; PI3K/AKT signaling pathway; TBI; microtubule associated protein 1 light chain 3; LC3; Tetrahydrocurcumin; Traumatic brain injury; Autophagy; Apoptosis
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2016.07.014

Abstract Background Tetrahydrocurcumin provides neuroprotection in multiple neurological disorders by modulating oxidative stress, inflammatory responses and autophagy. However, in traumatic brain injury (TBI), it is unclear whether a beneficial effect of Tetrahydrocurcumin exists. In this study, we hypothesized that administration of Tetrahydrocurcumin provides neuroprotection in a rat model of TBI. Material and methods Behavioral studies were performed by recording and analyzing beam-walking scores. The role of Tetrahydrocurcumin on neurons death was assessed via Nissl staining. We then performed western blot analyses, terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assays and immunofluorescence staining to evaluate autophagy and apoptosis. Phospho-protein kinase B (p-AKT) was also assessed via western blotting. Results Our data indicated that administration of Tetrahydrocurcumin alleviated brain edema, attenuated TBI-induced neuron cell death, decreased the degree of apoptosis and improved neurobehavioral function, which were accompanied by enhanced autophagy and phospho-AKT following TBI. Moreover, the autophagy inhibitor 3-MA and the PI3K kinase inhibitor LY294002 partially reversed the neuroprotection of Tetrahydrocurcumin after TBI. Conclusion This study indicates that Tetrahydrocurcumin protects neurons from TBI-induced apoptotic neuronal death, which may be through modulation autophagy and PI3K/AKT pathways. Thus, Tetrahydrocurcumin may be an attractive therapeutic agent for TBI.