3BDO Alleviates Seizures and Improves Cognitive Function by Regulating Autophagy in Pentylenetetrazol (PTZ)-Kindled Epileptic Mice Model.

3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3 H)-one (3BDO) is a mTOR agonist that inhibits autophagy. The main purpose of this study is to investigate the effects of 3BDO on seizure and cognitive function by autophagy regulation in pentylenetetrazol (PTZ)-kindled epileptic mice model. The PTZ-kindled epileptic mice model was used in study. The behavioral changes and electroencephalogram (EEG) of the mice in each group were observed. The cognitive functions were tested by Morris water maze test. The loss of hippocampal neurons was detected by hematoxylin-eosin (HE) staining and immunofluorescence analysis. Immunohistochemistry, western blot and q-PCR were employed to detect the expression of autophagy-related proteins and mTOR in the hippocampus and cortex. Less seizures, increased hippocampal neurons and reduced astrocytes of hippocampus were observed in the 3BDO-treated epileptic mice than in the PTZ-kindled epileptic mice. Morris water maze test results showed that 3BDO significantly improved the cognitive function of the PTZ-kindled epileptic mice. Western blot analyses and q-PCR revealed that 3BDO inhibited the expression of LC3, Beclin-1, Atg5, Atg7 and p-ULK1/ULK1, but increased that of p-mTOR/mTOR, p-P70S6K/P70S6K in the hippocampus and temporal lobe cortex of epileptic mice. Immunohistochemistry and immunofluorescence also showed 3BDO inhibited the LC3 expression and increased the mTOR expression in the hippocampus of epileptic mice. In addition, the autophagy activator EN6 reversed the decrease in the 3BDO-induced autophagy and aggravated the seizures and cognitive dysfunction in the epileptic mice. 3BDO regulates autophagy by activating the mTOR signaling pathway in PTZ-kindled epileptic mice model, thereby alleviating hippocampus neuronal loss and astrocytes proliferation, reducing seizures and effectively improving cognitive function. Therefore, 3BDO may have potential value in the treatment of epilepsy.

HDAC9 in the Injury of Vascular Endothelial Cell Mediated by P38 MAPK Pathway.

Ischemic stroke caused by atherosclerosis (AS) poses a serious threat to human life expectancy and quality. With the development of genome-wide association studies, the association of histone deacetylase 9 (HDAC9) expression of atheromatous plaques with ischemic stroke in large arteries has been revealed, but the molecular mechanisms behind this phenomenon have not been elucidated. In this study, we explored the effect of HDAC9 on the P38 mitogen activated protein kinase (P38 MAPK), a classic cellular inflammation-related pathway, by knocking down HDAC9 in vascular endothelial cells with short hairpin RNA (shRNA) and found that HDAC9 may mediate oxidized low density lipoprotein (ox-LDL)-induced inflammatory injury in vascular endothelial cells by regulating the phosphorylation level of P38 MAPK to lead to AS. It can be seen that HDAC9 may be a target to control the formation of atherosclerotic plaques. In follow-up experiments, it was verified that sodium valproate (SVA), as a HDAC9 inhibitor, can indeed antagonize the inflammatory damage of vascular endothelial cells, as well as SB203580, which is a P38 MAPK inhibitor. It proves that SVA may be a potential drug for the prevention and treatment of ischemic stroke.

An epidemiological survey of epilepsy in tropical rural areas of China.

OBJECTIVE: Epilepsy is a chronic neurological disease that is characterized by seizures. Seizure episodes, stigma, and high medical costs associated with this condition caused significant psychological distress. This study aimed to evaluate epidemiological characteristics and treatment status of epilepsy in individuals existing in the tropical rural areas of Hainan Province of China. METHODS: A household survey on epilepsy was conducted among the rural population of Chengmai County, Danzhou City, Baoting Autonomous County (Li and Miao nationalities), and Dingan County in Hainan Province, China. A screening questionnaire based on the standard screening questionnaires of the World Health Organization (WHO) was designed and a screening instrument of International Community-based Epilepsy Research Group was used. Individuals suspected or previously diagnosed with epilepsy were reexamined by an experienced neurologist. Further clinical data were collected from subjects with confirmed diagnosis of epilepsy. RESULTS: This study included 16 676 subjects with 8827 men (52.93%) and 7849 women (47.07%). Majority of the study subjects included were of Han Chinese (N = 13 145, 78.83%), and the remaining were of Li minority ethnicity. The incidence of epilepsy was 0.24 per 1000, and the total prevalence of active epilepsy was 2.33 per 1000. The prevalence of epilepsy in the Han and Li nationalities was 3.27 and 2.27 per 1000, respectively, which was shown to be higher in people aged ≥ 60. The initial onset of epilepsy tended to trigger among children aged between 0 and 9 years old. Initial assessment revealed that the treatment gap for active epilepsy was 58.97%, and stroke is shown as the most common cause of symptomatic epilepsy. SIGNIFICANCE: The prevalence and incidence of epilepsy in tropical rural areas of Hainan Province were close to those of the earlier findings that are reported in other regions of China and lower than those remaining in the tropical areas around the world. There exists a huge treatment gap for active epilepsy, which indicates an urgent need for a rational intervention strategy.