Ginkgo biloba Enhances the Anticonvulsant and Neuroprotective Effects of Sodium Valproate Against Kainic Acid-induced Seizures in Mice

2011 ◽  
Vol 6 (8) ◽  
pp. 679-690 ◽  
Author(s):  
B.A. Abdel-Waha ◽  
M.E. Metwally
Keyword(s):  
Kainic Acid ◽  
Sodium Valproate ◽  
Ginkgo Biloba ◽  
Neuroprotective Effects

scholarly journals Sodium valproate protects against neuronal ferroptosis in epilepsy via suppressing lysyl oxidase

2020 ◽  
Author(s):  
Qin Li ◽  
Qiu-Qi Li ◽  
Ji-Ning Jia ◽  
Zhao-Qian Liu ◽  
Hong-Hao Zhou ◽  
...  
Keyword(s):  
Western Blot ◽  
Kainic Acid ◽  
Sodium Valproate ◽  
Cell Injury ◽  
Cell Damage ◽  
Damage Model ◽  
Epileptic Seizures ◽  
Neuroprotective Effects ◽  
Injury Model ◽  
Ht22 Cell

AbstractBackground and purposeEpilepsy is a chronic neurological disease that is characterized by repetitive seizures. Seizures-related complications such as cognitive deficits, anxiety and sleep disorders seriously impact the life quality of patients. Antiepileptic drugs are widely used for the treatment of epilepsy. Sodium valproate is served as the first-line antiepileptic drugs and possesses various pharmacological effects on the brain. Sodium valproate exerts neuroprotective effects in acute nervous system diseases such as ischemic brain damage by inhibiting oxidative stress. However, the mechanism of neuroprotection of sodium valproate in epilepsy is unclear. Lysyl oxidase (Lox) is a monoamine oxidase that acts on extracellular matrix collagen and elastin and it can promote accumulation of oxidative stress. Our previous studies have confirmed that Lox is involved in ferroptosis, a novel iron-dependent and lipid peroxidation-mediated cell death pathway, during epilepsy. In this study, we would like to investigate whether sodium valproate can exert neuroprotective effects on kainic acid-induced epileptic seizures by inhibiting Lox-mediated ferroptosis.MethodsEpileptic mouse models were established by intracranial injection of 250 ng/μl kainic acid on right hippocampus. Sodium valproate and ferroptosis inhibitors were administrated by intraperitoneal injecting. The epileptic behavior of the mice within 4 hours was recorded after intracranial injection of kainic acid. Mouse hippocampus was acquired to analyze the mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and the production of 4-hydroxynonenal (4-HNE). In vitro, the protective effects of sodium valproate on glutamate-induced HT22 cell damage model was assessed by PI/Hoechst staining; The levels of PTGS2, 4-HNE and lipid ROS were analyzed by RT-qPCR, western blot and flow cytometry, respectively. RT-qPCR and Western blot analysis the mRNA and protein expression of Lox in the glutamate-induced HT22 cell damage model. The Lox overexpression model was established by intracranial injection of AAV on right hippocampus.ResultsPretreatment with sodium valproate and ferroptosis inhibitors could significantly alleviate the epileptic seizures in the kainic acid induced epilepsy mouse model. Western blot and RT-qPCR results showed that sodium valproate and ferroptosis inhibitors significantly inhibited the levels of 4-HNE and PTGS2. PI/Hoechst staining showed that 1 mM sodium valproate exerted protective effect on glutamate-induced HT22 cell injury model. There was no significant difference observed between sodium valproate and ferroptosis inhibitors co-intervention group and sodium valproate intervention group on glutamate-induced cell injury model. And sodium valproate could significantly inhibit the production of lipid reactive oxygen species and 4-HNE. The expression of Lox was significantly increased in the glutamate-induced HT22 cell injury model, which could be reversed by pretreatment of sodium valproate. And β-aminopropionitrile (a specific inhibitor of Lox) could inhibit ferroptosis induced by glutamate, as well as ameliorate the epileptic seizures in the kainic acid induced epilepsy mouse model. Pretreatment with sodium valproate could not ameliorate the epileptic behavior in the Lox-overexpression mice. Western blot analysis showed that sodium valproate could not suppress the production of 4-HNE in kainic acid induced epileptic mice model.ConclusionsThe neuroprotective effect of sodium valproate in epileptic seizures is closely related to the inhibition of ferroptosis. The inhibition of ferroptosis is involved in the neuroprotective effect of sodium valproate on glutamate-induced HT22 cell damage model. Sodium valproate may exert neuroprotective effects in kainic acid-induced epileptic seizures by abrogating Lox-mediated ferroptosis.

Sodium Valproate Ameliorates Neuronal Apoptosis in a Kainic Acid Model of Epilepsy via Enhancing PKC-Dependent GABAAR γ2 Serine 327 Phosphorylation

2018 ◽  
Vol 43 (12) ◽  
pp. 2343-2352 ◽  
Author(s):  
Qin Li ◽  
Qiu-Qi Li ◽  
Ji-Ning Jia ◽  
Shan Cao ◽  
Zhi-Bin Wang ◽  
...  
Keyword(s):  
Kainic Acid ◽  
Sodium Valproate ◽  
Neuronal Apoptosis

scholarly journals Xenon Exerts Neuroprotective Effects on Kainic Acid-Induced Acute Generalized Seizures in Rats via Increased Autophagy

2020 ◽  
Vol 14 ◽  
Author(s):  
Wei Zhu ◽  
Jianguo Zhu ◽  
Shengfa Zhao ◽  
Jieqing Li ◽  
Dianjun Hou ◽  
...  
Keyword(s):  
Kainic Acid ◽  
Neuroprotective Effects ◽  
Generalized Seizures

Neuroprotective Effects of the Absence of JNK1 or JNK3 Isoforms on Kainic Acid-Induced Temporal Lobe Epilepsy-Like Symptoms

2017 ◽  
Author(s):  
Luisa de Lemos ◽  
Felix Junyent ◽  
Antoni Camins ◽  
Rubén Darío Castro-Torres ◽  
Jaume Folch ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Kainic Acid ◽  
Temporal Lobe ◽  
Neuroprotective Effects

scholarly journals Neuroprotective Effects of Ganoderma curtisii Polysaccharides After Kainic Acid-Seizure Induced

2019 ◽  
Vol 11 (5) ◽  
pp. 1046-1054
Author(s):  
Ismael Leon-Rivera ◽  
Juana Villeda-Hernandez ◽  
Elizur Montiel-Arcos ◽  
Isaac Tello ◽  
Maria Yolanda Rios ◽  
...  
Keyword(s):  
Kainic Acid ◽  
Neuroprotective Effects

Ginkgo biloba and Its Constituent 6-hydroxykynurenic-acid as well as Its Proanthocyanidins Exert Neurorestorative Effects against Cerebral Ischemia

Planta Medica ◽  
2020 ◽  
Vol 86 (10) ◽  
pp. 696-707
Author(s):  
Jianbiao Yao ◽  
Hongxiang Qiao ◽  
Zhuming Jin ◽  
Ruwei Wang ◽  
Haibo Huang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ginkgo Biloba ◽  
Ischemia Reperfusion ◽  
Grape Seed ◽  
Negative Control ◽  
Major Contributor ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Phenolic Constituents

AbstractNeuroprotective effects against cerebral ischemia/reperfusion (I/R) injury by Ginkgo biloba leaves are commonly attributed to the antioxidant activity of its proanthocyanidins. Furthermore, preliminary experiments identified 6-hydroxykynurenic acid (6-HKA) as a major contributor to this effect of extract of G. biloba leaves (EGb) prepared according to the Chinese Pharmacopoeia (ChP). In order to elucidate the specific contribution of both proanthocyanidins and 6-HKA to the overall neurorestorative effects of this extract according to ChP, EGb ChP was separated into pure 6-HKA and a newly developed Ginkgo proanthocyanidin extract (GPE), enriched in proanthocyanidins but not containing 6-HKA. Male Sprague-Dawley rats were divided into the groups: sham: 8; model (placebo): 25; GPE 80 mg/kg: 13; GPE 40 mg/kg: 13; GPE 20 mg/kg: 16; grape seed extract (negative control) 40 mg/kg: 18; nimodipine (positive control) 2 mg/kg: 8. All non-sham animals were subjected to cerebral I/R injury by occluding the middle cerebral artery with a nylon suture that was removed after 2 h of ischemia to establish reperfusion. For comparison, a parallel series of experiments were performed with 6-HKA. In these in vivo experiments, neurological dysfunctions were reduced by both GPE and 6-HKA, and both average infarct size and concentrations of malondialdehyde (MDA) and super oxide dismutase (SOD) were significantly ameliorated as compared to the model group. This data, therefore, demonstrates that the neuroprotective effects of EGb cannot be explained by a purely chemical antioxidative effect alone as has been previously proposed, especially with regards to the proanthocyanidins. A pharmacological neurorestorative effect of EGb on neurons and brain tissue itself seems to be a much more straightforward explanation for the presented observations. This effect is most likely explained by the synergistic action of both its numerous phenolic constituents (GPE) and 6-hydroxykynurenic acid (6-HKA), which could be identified as one major contributor to the observed activity.

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