Neuroprotective effect of astaxanthin on newborn rats exposed to prenatal maternal seizures.

Maternal epilepsy during pregnancy is associated with an increased incidence of brain damage and cognitive deficits in offspring. Oxidative stress is believed to play a critical role in this process. Astaxanthin, a natural carotenoid and dietary supplement, possesses potent antioxidant properties. This study was designed to investigate whether astaxanthin ameliorates the hippocampal damage in newborn rats induced by maternal epileptic seizures in utero and to explore the underlying mechanisms. Female Sprague-Dawley rats underwent chronic amygdalar kindling. After being fully kindled, all rats were allowed to mate, and electrical stimulation in the amygdala was performed every other day throughout the pregnancy. Astaxanthin was intraperitoneally injected at a dose of 30 mg/kg/d throughout pregnancy. Prenatal astaxanthin administration ameliorated neuronal lesions, decreased oxidative stress and induced the expression of cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus of pups. Astaxanthin also ameliorated placental ischemic damage in epileptic mothers. Based on the results of the present study, we concluded that astaxanthin might serve as a therapeutic agent for preventing brain damage in offspring exposed to prenatal maternal seizures.

(-)-Epigallocatechin-3-Gallate Protects Against Lithium-Pilocarpine-Induced Epilepsy by Inhibiting the Toll-Like Receptor 4 (TLR4)/Nuclear Factor-κB (NF-κB) Signaling Pathway.

BACKGROUND Temporal lobe epilepsy (TLE) is the most common type of intractable epilepsy in humans, and it is often accompanied by cognitive impairment. In this study, we examined the effects of (-)-Epigallocatechin-3-gallate (EGCG) after SE on behavior in the rat lithium-pilocarpine model of TLE. MATERIAL AND METHODS The rats were randomly divided into 3 groups: (1) the control group, in which 12 rats received no treatment); (2) the epilepsy (EP) group, in which 15 rats were treated with saline after status epilepticus (SE); and (3) the EP+EGCG group, in which 15 rats were treated with EGCG (25 mg/kg/d, intraperitoneal) after SE. The SE model was induced with lithium chloride-pilocarpine, and electroencephalography and a high-definition camera were used to monitor SRS. The Morris water maze test and hippocampal late-phase long-term potentiation (L-LTP) recordings were used to evaluate cognitive impairment, and TLR4, NF-kappaB, and IL-1ß levels were determined using Western blot analysis. RESULTS We concluded that EGCG treatment after SE (1) markedly reduced SRS frequency in pilocarpine-treated rats, (2) improved epilepsy-induced cognitive impairment and reversed epilepsy-induced synaptic dysfunction in L-LTP in vivo, (3) protected hippocampal neurons from damage after SRS, and (4) significantly attenuated the increase in TRL-4 and IL-1ß hippocampal levels. The above findings clearly show that EGCG exerts antiepileptogenesis and neuroprotective effects on pilocarpine-induced epilepsy. CONCLUSIONS We found that EGCG can suppress seizures and inhibit hippocampal neuronal apoptosis, as well as improving cognitive function of epileptic rats. Our findings suggest that EGCG may a novel adjuvant therapeutic approach in epilepsy by improving epileptic behavior and cognitive dysfunction.

Salidroside protects against kainic acid-induced status epilepticus via suppressing oxidative stress.

There are numerous mechanisms by which the brain generates seizures. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Salidroside (SDS) extracted from Rhodiola rosea L. shows multiple bioactive properties, such as neuroprotection and antioxidant activity in vitro and in vivo. This study explored the role of SDS in kainic acid (KA)-induced SE and investigated the underlying mechanism. Latency to SE increased in the SDS-pretreated mice compared to the KA group, while the percentage of incidence of SE was significantly reduced. These results suggested that pretreatment with SDS not only delayed SE, but it also decreased the incidence of SE induced by KA. KA increased MDA level and reduced the production of SOD and GSH at multiple timepoints after KA administration. SDS inhibited the change of MDA, SOD and GSH induced by KA prior to SE onset, indicating that SDS protects against KA-induced SE via suppressing oxidative stress. Based on these results, we investigated the possible molecular mechanism of SDS. Pretreatment with SDS reversed the KA-induced decrease in AMP-activated protein kinase (AMPK); increased the sirtuin 1 (SIRT1) deacetylase activity in KA-treated mice, which had no demonstrable effect on SIRT1 mRNA and protein; and suppressed the KA-induced increase in Ace-FoxO1. These results showed that AMPK/SIRT1/FoxO1 signaling is possibly the molecular mechanism of neuroprotection by SDS.