Cognitive impairment is not only associated with seizures but also reported as an adverse effect of antiepileptic drugs. Thus, new molecules that can ameliorate seizures and maintain satisfactory cognitive function should be developed. The antiepileptic potential of asiatic acid, a triterpene derived from the medicinal herb Centella asiatica, has already been demonstrated; however, its role in epilepsy-related cognitive deficits is yet to be determined. In this study, we evaluated the effects of asiatic acid on cognitive deficits in rats with kainic acid (KA)-induced seizure and explored the potential mechanisms underlying these effects. Our results revealed that asiatic acid administrated intraperitoneally 30 min prior to KA (15 mg/kg) injection ameliorated seizures and significantly improved KA-induced memory deficits, as demonstrated by the results of the Morris water maze test. In addition, asiatic acid ameliorated neuronal damage, inhibited calpain activation, and increased protein kinase B (AKT) activation in the hippocampus of KA-treated rats. Asiatic acid also increased the levels of synaptic proteins and the number of synaptic vesicles as well as attenuated mitochondrial morphology damage in the hippocampus of KA-treated rats. Furthermore, proteomic and Western blot analyses of hippocampal synaptosomes revealed that asiatic acid reversed KA-induced changes in mitochondria function-associated proteins, including lipoamide dehydrogenase, glutamate dehydrogenase 1 (GLUD1), ATP synthase (ATP5A), and mitochondrial deacetylase sirtuin-3 (SIRT3). Our data suggest that asiatic acid can prevent seizures and improve cognitive impairment in KA-treated rats by reducing hippocampal neuronal damage through the inhibition of calpain activation and the elevation of activated AKT, coupled with an increase in synaptic and mitochondrial function.

Silymarin, a polyphenoic flavonoid derived from the seeds of milk thistle (Silybum marianum), exhibits neuroprotective effects. In this study, we used a model of rat cerebrocortical synaptosomes to investigate whether silymarin affects the release of glutamate, an essential neurotransmitter involved in excitotoxicity. Its possible neuroprotective effect on a rat model of kainic acid (KA)-induced excitotoxicity was also investigated. In rat cortical synaptosomes, silymarin reduced glutamate release and calcium elevation evoked by the K⁺ channel blocker 4-aminopyridine but did not affect glutamate release caused by the Na⁺ channel activator veratridine or the synaptosomal membrane potential. Decreased glutamate release by silymarin was prevented by removal of extracellular calcium and blocking of N- and P/Q-type Ca²⁺ channel or extracellular signal-regulated kinase 1/2 (ERK1/2) but not by blocking of intracellular Ca²⁺ release. Immunoblotting assay results revealed that silymarin reduced 4-aminopyridine-induced phosphorylation of ERK1/2. Moreover, systemic treatment of rats with silymarin (50 or 100 mg/kg) 30 min before systemic KA (15 mg/kg) administration attenuated KA-induced seizures, glutamate concentration elevation, neuronal damage, glial activation, and heat shock protein 70 expression as well as upregulated KA-induced decrease in Akt phosphorylation in the rat hippocampus. Taken together, the present study demonstrated that silymarin depressed synaptosomal glutamate release by suppressing voltage-dependent Ca²⁺ entry and ERK1/2 activity and effectively prevented KA-induced in vivo excitotoxicity.

Current anti-seizure drugs fail to control approximately 30% of epilepsies. Therefore, there is a need to develop more effective anti-seizure drugs, and medicinal plants provide an attractive source for new compounds. This study aimed to evaluate the possible anti-seizure and neuroprotective effects of neferine, an alkaloid from the lotus seed embryos of Nelumbo nucifera, in a kainic acid (KA)-induced seizure rat model and its underlying mechanisms. Rats were intraperitoneally (i.p.) administrated neferine (10 and 50 mg/kg) 30 min before KA injection (15 mg/kg, i.p.). Neferine pretreatment increased seizure latency and reduced seizure scores, prevented glutamate elevation and neuronal loss, and increased presynaptic protein synaptophysin and postsynaptic density protein 95 expression in the hippocampi of rats with KA. Neferine pretreatment also decreased glial cell activation and proinflammatory cytokine (interleukin-1β, interleukin-6, tumor necrosis factor-α) expression in the hippocampi of rats with KA. In addition, NOD-like receptor 3 (NLRP3) inflammasome, caspase-1, and interleukin-18 expression levels were decreased in the hippocampi of seizure rats pretreated with neferine. These results indicated that neferine reduced seizure severity, exerted neuroprotective effects, and ameliorated neuroinflammation in the hippocampi of KA-treated rats, possibly by inhibiting NLRP3 inflammasome activation and decreasing inflammatory cytokine secretion. Our findings highlight the potential of neferine as a therapeutic option in the treatment of epilepsy.

This study evaluated the effects of heart rate (HR) on brachial-ankle pulse wave velocity (baPWV) and ankle-brachial pressure index (ABI). Thirty-two patients without significant organic heart disease underwent elective cardiac catheterization or electrophysiologic study, and were then enrolled in right atrial pacing (RAP; 11 men, 9 women; aged 48 ∓15 years) or right ventricular pacing (RVP; 6 men, 6 women, aged 45 ∓13 years) studies. Three different HR levels (90, 100, and 110 beats per minute) were paced in random order. By stepwise, multiple linear regression analysis, age, systolic blood pressure (SBP), and pulse pressure (PP) correlated positively with baseline baPWV. In the RAP group, as HR increased, baPWV and left brachial diastolic blood pressure increased significantly (p ≤0.015), while ABI, left ankle SBP, left brachial PP, and left ankle PP decreased significantly (p ≤0.013). In the RVP group, as HR increased, baPWV also increased significantly (p=0.001), while ABI, left ankle SBP, and PP decreased significantly (p ≤ 0.034). Values of baPWV and ABI may be influenced by HR in young and middle-aged patients without significant organic heart disease. When these values are used to evaluate and follow up cardiovascular risk in patients, HR changes should be considered.

We define the weighted Carleson measure space $CMO^p_w$ using wavelets, where the weight function $w$ belongs to the Muckenhoupt class. Then we show that $CMO^p_w$ is the dual space of the weighted Hardy space $H^p_w$ by using sequence spaces. As an application, we give a wavelet characterization of $BMO_w$ .