SREBP1 deficiency diminishes glutamate-mediated HT22 cell damage and hippocampal neuronal pyroptosis induced by status epilepticus.

Status epilepticus (SE) is a life-threatening disorder that can result in death or severe brain damage, and there is a substantial body of evidence suggesting a strong association between pyroptosis and SE. Sterol regulatory element binding protein 1 (SREBP1) is a significant transcription factor participating in both lipid homeostasis and glucose metabolism. However, the function of SREBP1 in pyroptosis during SE remains unknown. In this study, we established a SE rat model by intraperitoneal injection of lithium chloride and pilocarpine in vivo. Additionally, we treated HT22 hippocampal cells with glutamate to create neuronal injury models in vitro. Our results demonstrated a significant induction of SREBP1, inflammasomes, and pyroptosis in the hippocampus of SE rats and glutamate-treated HT22 cells. Moreover, we found that SREBP1 is regulated by the mTOR signaling pathway, and inhibiting mTOR signaling contributed to the amelioration of SE-induced hippocampal neuron pyroptosis, accompanied by a reduction in SREBP1 expression. Furthermore, we conducted siRNA-mediated knockdown of SREBP1 in HT22 cells and observed a significant reversal of glutamate-induced cell death, activation of inflammasomes, and pyroptosis. Importantly, our confocal immunofluorescence analysis revealed the co-localization of SREBP1 and NLRP1. In conclusion, our findings suggest that deficiency of SREBP1 attenuates glutamate-induced HT22 cell injury and hippocampal neuronal pyroptosis in rats following SE. Targeting SREBP1 may hold promise as a therapeutic strategy for SE.

Unnatural deaths in Shanghai from 2000 to 2009: a retrospective study of forensic autopsy cases at the Shanghai Public Security Bureau.

Shanghai is the most developed city in China and has a soaring population. This study uses forensic epidemiology to determine the relationship between unnatural deaths and the development in Shanghai, based on recently released forensic autopsy cases from the 2000s at the Shanghai Public Security Bureau (SPSB). There were 5425 accidental deaths, 2696 homicides, 429 suicides, 186 natural deaths, and 1399 deaths of undetermined cause. There was a male-to-female ratio of 2.02:1, and the average age was 40.9±18.7 years. Traffic accidents (84.2%) were the number one cause of accidental deaths, which decreased during the study period. Sharp force injury (50.6%) was the leading cause of homicides, different from Western countries, where firearms are the leading cause. Hanging (24.5%) was the leading cause of suicides, whereas drug and chemical intoxication was the leading cause in the previous decade; pesticide ingestion decreased in the 2000s. In addition to traffic accidents, manual strangulation was the leading cause of death in childhood fatalities. Children under age 2 were vulnerable to homicides. In the 2000s, there were a large number of drug overdoses, and illegal medical practices and subway-related deaths first appeared in Shanghai. A new type of terrorist attack that involved injecting people with syringes in public places was reflected in the SPSB archives. The forensic epidemiology and changes in unnatural deaths in this decade reflected their relationship with the law, policy and changes in Shanghai. Illegal medical practices, subway-related deaths and terrorist attacks were closely related to the development in Shanghai. Identifying the risks of unnatural deaths will improve public health.

eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells.

OBJECTIVE: We investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K)/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs). METHODS: Cortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR. RESULTS: Mdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs. CONCLUSIONS: eEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent.

Suicidal drownings with psychiatric disorders in Shanghai: a retrospective study from 2010.1 to 2014.6.

Psychiatric disorders exhibited in 13% suicidal drownings in Southwestern Croatia and 63% in Milan, but in China is unknown. This study is committed to outline the feature of a suicidal drowning with psychiatric disorder, show mental status and reveal key factor to high incidence in China. Immersed corpses were handled by SPSBMPH in its jurisdiction range. Half of immersed corpses were suicidal, and nearly half of suicides had psychiatric disorders. 104 suicidal drownings with psychiatric disorders cases from 2010.1 to 2014.6 were reviewed (21.5% of all immersed corpses, 42.1% of suicides). Most victims clothed normally, and only 2 fastened attached weights. Male victims were more and younger than female. Psycho were prone to commit suicidal drowning in warm and hot season. Psycho were prone to choose familiar area to commit suicide, 45 decedents were found in their familiar areas. Suicidal drowings were occult without suicide attempts, suicide note or abnormal clothing, but showed abnormal mental or behavior changes prior to suicide. The three leading psychiatric disorders were depression (33.7%), depression status (30.8%) and schizophrenia (20.2%). Only 44.2% decedents had visited psychiatric disorder specialist, and merely less than 10% patients could adhere to regular medication. No regular medication on psychiatric disorder was the key factor contributing to high incidence of suicide in psycho. Professional psychiatric and psychological intervention should be taken as soon as possible when they had psychiatric symptoms or suffered misfortune. Guardians should be alert to patients' abnormality to detect their suicidal ideation and intervene, especially in warm season.

Tenidap is neuroprotective in a pilocarpine rat model of temporal lobe epilepsy.

BACKGROUND: Tenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 (COX-2) and cytokines in vitro. This study aimed to evaluate the neuroprotective effect of tenidap in a pilocarpine rat model of temporal lobe epilepsy (TLE). METHODS: Tenidap was administered daily at 10 mg/kg for 10 days following pilocarpine-induced status epilepticus (SE) in male Wistar rats after which prolonged generalized seizures resulted in TLE. After tenidap treatment, spontaneous recurrent seizures (SRSs) were recorded by video monitoring (for 7 hours per day for 14 days). The frequency and severity of the SRSs were observed. Histological and immunocytochemical analyses were used to evaluate the neuroprotective effect of tenidap and detect COX-2 expression, which may be associated with neuronal death. RESULTS: There were 46.88 ± 10.70 survival neurons in tenidap-SE group, while there were 27.60 ± 5.18 survival neurons in saline-SE group at -2.4 mm field in the CA3 area. There were 37.75 ± 8.78 survival neurons in tenidap-SE group, while there were 33.40 ± 8.14 survival neurons in saline-SE group at -2.4 mm field in the CA1 area. Tenidap treatment significantly reduced neuronal damage in the CA3 area (P < 0.05) and slightly reduced damage in the CA1 area. Tenidap markedly inhibited COX-2 expression in the hippocampus, especially in the CA3 area. CONCLUSION: Tenidap conferred neuroprotection to the CA3 area in a pilocarpine-induced rat model of TLE by inhibiting COX-2 expression.