Wogonin preventive impact on hippocampal neurodegeneration, inflammation and cognitive defects in temporal lobe epilepsy

Abstract

Previous studies demonstrated that the pathophysiological changes after temporal lobe epilepsy (TLE) such as oxidative stress, inflammatory reaction contribute to cognitive defect and neuronal damage. The present study was conducted to evaluate the anticonvulsant effect of wogonin ameliorates kainate-induced TLE, and to investigate the mechanism underlying these effects. Rats were divided into control, wogonin, kainate, and wogonin-pretreated kainate groups. The rat model of TLE was induced by unilateral intrahippocampal injection of 0.4 ug/ul of kainate. The results showed that the cognitive function in TLE rats was significantly impaired, and wogonin treatment improved cognitive function in the Morris water maze (MWM). H & E staining and TUNEL staining showed obvious damage in the hippocampus of TLE rats, and wogonin alleviated the damage. To evaluate the oxidative stress, the expression of MDA and GSH in plasma were detected. Nrf-2 and HO-1 mRNA expression in the hippocampus were detected. The levels of MDA in plasma increased in TLE rats, and the levels of GSH in plasma and Nrf-2, HO-1 in the brain decreased. Treatment with wogonin alleviated these changes. We also detected the mRNA expression of inflammatory mediators like IL-1β, TNF-α, and NF kB in the brain. The inflammatory reaction was significantly activated in the brain of TLE rats, and wogonin alleviated neuroinflammation. We detected the mRNA expression of Bcl-2, Bax, caspase-3, in the hippocampus. The levels of Bcl-2 decreased in TLE rats, Bax and caspase-3 increased, while wogonin alleviated these changes. The present study indicated that wogonin exerted a noticeable neuroprotective effect in kainate-induced TLE rats.

Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy

“…These results indicate that there may be positive feedback between proinflammatory cytokines and SerpinA3N. Consistent with previous studies [ 74 , 75 ], we found that the key proteins of the NF-κB signaling pathway were significantly activated in mice with TLE or in mice overexpressing SerpinA3N without KA treatment. In epileptic mice after NF-κB inhibitor treatment or pretreatment with SerpinA3N knockdown, the expression levels of proinflammatory cytokines were decreased.…”

Antioxidant Therapy Reduces Oxidative Stress, Restores Na,K-ATPase Function and Induces Neuroprotection in Rodent Models of Seizure and Epilepsy: A Systematic Review and Meta-Analysis

“…There was also a reduction in GSH levels in the brains of PTZ-induced rats; however, no change in GSH levels was observed after the use of exogenous antioxidants [80]. Regarding GSH levels in the hippocampus, our results were also confirmed by other studies that did not meet the eligibility criteria of this meta-analysis, showing that when the hippocampus is evaluated separately from the rest of the brain there is an increase in GSH after the use of antioxidant therapy [32,[81][82][83].…”

Ursolic Acid Protects Neurons in Temporal Lobe Epilepsy and Cognitive Impairment by Repressing Inflammation and Oxidation

“…The acute increased mitochondrial oxidative stress following protracted seizure causes oxidative damage to mtDNA ( Waldbaum and Patel, 2010 ). Furthermore, mitochondrial dysfunction is involved in the excitotoxicity induction of neuronal death ( Green and Reed, 1998 ) and contributes to seizure-induced hippocampal cell loss and cognitive defects ( Waldbaum and Patel, 2010 ; Kovac et al, 2017 ; Guo et al, 2020 ). Herein, we clarified the notable anti-seizure and neuroprotective properties of UA in pilocarpine-induced epileptic rats.…”