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| Effects of Esketamine on Neuronal Damage Inflammation and AMPK/NF-κB Signaling Pathway in Rats with Traumatic Brain Injury |
| LIU Xuan, TENG Jinliang, YUAN Li, et al |
| The First Hospital Affiliated to Hebei North University, Hebei Zhangjiakou 075061, China |
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Abstract Objective: To investigate the effects of esketamine on neuronal injury, inflammation and adenosine monophosphate activated protein kinase (AMPK)/nuclear factor-κB (NF-κB) signaling pathway in rats with traumatic brain injury (TBI). Methods: According to the random number table, the rats were divided into sham operation group, model group, esketamine group (50 mg/kg), AMPK inhibitor group (20 mg/kg), and esketamine+AMPK inhibitor group (50 mg/kg+20 mg/kg). TBI rat models were established in groups except the sham operation group, and each group was given corresponding intervention for 7 days. Modified neurological severity score (mNSS) was used to evaluate the neural function of rats; serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay; HE staining was used to observe the pathological changes of the brain tissue around the lesion; Nissner staining was used to observe the damage of neurons in the brain surrounding the lesion; TUNEL was used to detect the apoptosis of neurons in the brain surrounding the lesion; detection of AMPK/NF-κB pathway protein expression in the brain tissue around the injured focus of rats by Western blot. Results: Compared with the sham group, rats in the model group showed severe lesions and neuronal damage around the foci of injury. mNSS score, serum IL-6, TNF-α, neuronal apoptosis number, phosphorylated NF-κB p65 (p-NF-κB p65)/NF-κB p65 protein expression were significantly increased, and phosphorylated AMPK (p-AMPK)/AMPK protein expression was significantly decreased (P<0.05). Compared with the model group, the brain tissue pathological condition and neuronal damage around the injury foci were improved in the esketamine group. mNSS score, serum IL-6, TNF-α, neuronal apoptosis number, p-NF-κB p65/NF-κB p65 protein expression was significantly reduced and p-AMPK/AMPK protein expression was significantly increased in the AMPK inhibitor group (P<0.05). In rats, brain tissue lesions and neuronal damage around the injury foci were aggravated, and mNSS score, serum IL-6, TNF-α, neuronal apoptosis number, p-NF-κB p65/NF-κB p65 protein expression were significantly increased and p-AMPK/AMPK protein expression were significantly decreased (P<0.05). The changes in each of these indices in the esketamine + AMPK inhibitor group were between the esketamine and AMPK inhibitor groups. Conclusion: Esketamine can alleviate the neuronal injury and inflammatory reaction in TBI rats, which may be related to the regulation of AMPK/NF-κB pathway.
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2023, Vol. 29 
