Posttraumatic administration of a sub-anesthetic dose of ketamine exerts neuroprotection via attenuating inflammation and autophagy. (20th February 2017)

• Record Type: Journal Article
• Authors: Wang, C.-Q.; Ye, Y.; Chen, F.; Han, W.-C.; Sun, J.-M.; Lu, X.; Guo, R.; Cao, K.; Zheng, M.-J.; Liao, L.-C.
• Is Part Of: Neuroscience. Volume 343(2017)
• Page Start: 30
• Page End: 38
• Publication Date: 2017-02-20
• Subjects: mTOR mammalian target of rapamycin -- MWM Morris water maze -- NMDA N-methyl-d-aspartate -- NSS neurological severity score -- PCA perchloric acid -- TA target quadrant -- TBI traumatic brain injury; mTOR -- autophagy -- traumatic brain injury -- ketamine; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.11.029
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: The neuroprotection of ketamine at subanesthetic-dosage. ketamine at sub-anesthetic dose alleviates functional deficits after TBI. Posttraumatic administration of ketamine exerts anti-inflammatory properties. ketamine at sub-anesthetic dose may regulate autophagy and ameliorate secondary brain injury. Administration of 10 mg/kg ketamine, every 24 h up to 7 days. Abstract: As a complex disease, traumatic brain injury (TBI) can result in long-term psychiatric changes and sensorimotor and cognitive impairments. The TBI-induced loss of memory and long-term cognitive dysfunction are related to mechanistic factors including an increased inflammatory response, autophagy, edema, and ischemia. Many published studies have offered evidence for the neuroprotective effects and anti-inflammatory properties of ketamine for TBI patients. Nonetheless, there is a limited understanding of the accurate mechanism that underlies the potential neuroprotective effects of ketamine. Herein, it can be shown that posttraumatic administration of ketamine at a sub-anesthetic dose (10 mg/kg ketamine, every 24 h up to 7 days) can prevent the TBI-induced production of IL-6 and TNF-α, attenuate deficits of dendrites and spines and exert beneficial effects on memory and behavior. Moreover, studies show that ketamine may activate the mTOR signaling pathway by p -mTOR induction to down-regulate the expression of crucial autophagic proteins such as LC3 and Beclin-1. According to these findings, ameliorating secondary brain injury and anti-inflammatory properties is closely related to the neuroprotection of ketamine, which supports the use of ketamine as a potential therapy for patients with TBI to alleviate functional deficits.