Propofol mitigates brain injury and oxidative stress, and enhances GABAA receptor ?1 subunit expression in a rat model of lithium chloride-pilocarpine induced status epilepticus

Authors: Lei Li, Xiu Liu, Juan Du, Wangyan Yang, Runqiao Fu, Yunfeng Li, Wei Zhao, HENGLIN WANG

Abstract: Background/aim: Propofol is a positive allosteric modulator of GABAA receptor (GABAAR) and has potent antioxidant activity. The aim of this study was to investigate the effect of propofol on damage to the cerebral cortex and hippocampus in a lithium chloride (LiCl)- pilocarpine animal model of status epilepticus (SE). Materials and methods: Adult male Sprague Dawley rats were injected with LiCl-pilocarpine to induce SE. They were then randomized and injected 30 min later with vehicle saline (SE+saline), propofol (SE+PPF, 50 mg/kg), Diazepam (SE+DZP, 10 mg/kg), Scopolamine (SE+SCOP, 10 mg/kg), or MK-801 (SE+MK-801, 2 mg/kg). Another group of rats received saline only and served as the naïve control (BLK). The levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) in the serum, cortex and hippocampus were analyzed 2 and 24 h posttreatment. The degree of tissue damage in the cortex and hippocampus of individual rats was assessed 24 h posttreatment, together with expression of the GABAAR ?1 subunit. Results: The propofol group showed reduced levels of tissue damage in the cerebral cortex and hippocampus, decreased levels of MDA, and increased levels of GSH compared to the SE+saline group. No changes in SOD level were observed in serum and tissue samples from the cortex and hippocampus of SE+saline rats. Immunohistochemistry and Western blot assays showed that propofol treatment significantly increased the expression of GABAAR ?1 subunit in the cortical and hippocampal tissues of SE rats. Conclusion: Propofol treatment protected against SE-induced tissue injury in the cortex and hippocampus of rats. This was due at least in part to its antioxidant activity and to its induction of GABAAR ?1 subunit expression in the brain.

Keywords: Propofol, status epilepticus, antioxidant activity, GABAA receptor a1 subunit

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