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1.
Biomed Pharmacother ; 175: 116746, 2024 Jun.
Article En | MEDLINE | ID: mdl-38739991

Brain apoptosis is one of the main causes of epileptogenesis. The antiapoptotic effect and potential mechanism of Q808, an innovative anticonvulsant chemical, have never been reported. In this study, the seizure stage and latency to reach stage 2 of pentylenetetrazol (PTZ) seizure rat model treated with Q808 were investigated. The morphological change and neuronal apoptosis in the hippocampus were detected by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, respectively. The hippocampal transcriptomic changes were observed using RNA sequencing (RNA-seq). The expression levels of hub genes were verified by quantitative reverse-transcription PCR (qRT-PCR). Results revealed that Q808 could allay the seizure score and prolong the stage 2 latency in seizure rats. The morphological changes of neurons and the number of apoptotic cells in the DG area were diminished by Q808 treatment. RNA-seq analysis revealed eight hub genes, including Map2k3, Nfs1, Chchd4, Hdac6, Siglec5, Slc35d3, Entpd1, and LOC103690108, and nine hub pathways among the control, PTZ, and Q808 groups. Hub gene Nfs1 was involved in the hub pathway sulfur relay system, and Map2k3 was involved in the eight remaining hub pathways, including Amyotrophic lateral sclerosis, Cellular senescence, Fc epsilon RI signaling pathway, GnRH signaling pathway, Influenza A, Rap1 signaling pathway, TNF signaling pathway, and Toll-like receptor signaling pathway. qRT-PCR confirmed that the mRNA levels of these hub genes were consistent with the RNA-seq results. Our findings might contribute to further studies exploring the new apoptosis mechanism and actions of Q808.


Anticonvulsants , Apoptosis , Epilepsy , Gene Expression Profiling , Hippocampus , Pentylenetetrazole , Rats, Sprague-Dawley , Transcriptome , Animals , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Apoptosis/drug effects , Anticonvulsants/pharmacology , Male , Transcriptome/drug effects , Epilepsy/drug therapy , Epilepsy/chemically induced , Epilepsy/genetics , Gene Expression Profiling/methods , Rats , Disease Models, Animal , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Seizures/chemically induced , Seizures/genetics , Seizures/drug therapy
2.
BMC Neurosci ; 23(1): 7, 2022 02 03.
Article En | MEDLINE | ID: mdl-35114941

BACKGROUND: The gut microbiota can modulate brain function and behavior and is increasingly recognized as an important factor in mediating the risk of epilepsy and the effects of seizure interventions. Drug therapy is one of the factors that influence the composition of the intestinal microbiota. Q808 is an innovative chemical with strong anticonvulsant activity and low neurotoxicity. However, studies evaluating the effect of Q808 on gut microbial communities are lacking. In this study, we aimed to evaluate the anticonvulsant activity of Q808 on a pentylenetetrazol (PTZ)-induced seizure model and analyze and compare the intestinal microbiota composition of non-PTZ vehicle control group, the PTZ-induced seizure model rats with and without Q808, through 16S rDNA sequencing. Neurotransmitter levels in the hippocampus were quantitatively estimated using HPLC-MS. RESULTS: The results suggest that Q808 effectively alleviates seizures in chronic PTZ-kindled model rats. Additionally, based on the analyzed abundance of the gut microbiota, dysbacteriosis of model rats was found to be corrected after Q808 treatment at the phylum level. The unique bacterial taxa (e.g., Lactobacillus) that are associated with acetylcholine production, were significantly increased. Several short-chain fatty acids (SCFAs)-producing bacteria, including Roseburia, Alloprevptella, Prevotellaceae_NK3B31_group, Prevotellaceae_UCG-001, and Prevotella_9, were enriched. In the hippocampus, the contents of acetylcholine increased, whereas the levels of 3-methoxytyramine, glutamine, and 5-hydroxyindole acetic acid (5-HIAA) decreased after Q808 treatment. CONCLUSIONS: This study demonstrates that Q808 can be used to remodel the dysbiosis of the gut microbiome and influence neurotransmitter levels in the hippocampus of PTZ-induced seizure model rats. We hope that these novel findings prompt further research on the interaction between gut microbiota and seizures and the mechanism of Q808.


Gastrointestinal Microbiome , Pentylenetetrazole , Animals , Anticonvulsants/pharmacology , Hippocampus , Neurotransmitter Agents , Rats , Seizures/chemically induced , Seizures/drug therapy
3.
Int Heart J ; 60(4): 822-829, 2019 Jul 27.
Article En | MEDLINE | ID: mdl-31257338

Atrial fibrillation (AF) is an independent risk factor for intracranial hemorrhage in patients receiving recombinant-tissue-type plasminogen activator (rt-PA) thrombolytic therapy. Research showed that patients with acute ischemic stroke (AIS) could benefit from multimode computed-tomography- (CT-) guided intravenous thrombolysis over 4.5 hours. The medical data of patients with AIS in our center were retrospectively reviewed, and the data of the multimode CT-guided thrombolytic therapy or nonthrombolytic therapy within different time windows (3-9 hours) were evaluated. 134 AIS cases were selected successfully and divided into three groups: patients with AF treated by rt-PA (AF rt-PA), patients with AF not treated by rt-PA (AF non-rt-PA), and patients without AF treated by rt-PA (non-AF rt-PA). After correcting for the baseline NIH Stroke Scale (NIHSS), sex, age, and hypertension data, the comparison results showed that the NIHSS improved significantly at hospital discharge for rt-PA-treated patients (n = 47) compared to non-rt-PA-treated patients with AIS (n = 31) with AF (P = 0.0156). The NIHSS evaluation at 90 days of follow-up also improved in rt-PA-treated patients (P = 0.0157). The NIHSS at hospital discharge was higher in AF rt-PA-treated patients compared to non-AF rt-PA-treated patients (P = 0.0167) after correction; the difference was not statistically significant at 90 days of follow-up (P = 0.091). Our research showed that the neural function improved after 3-9 hours of thrombolytic therapy with rt-PA in patients with AIS and AF. If there is no thrombolytic taboo, the patients could benefit from the thrombolytic therapy, although the onset time window has been extended to 9 hours.


Atrial Fibrillation/complications , Brain Ischemia/drug therapy , Multidetector Computed Tomography/methods , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/administration & dosage , Acute Disease , Administration, Intravenous , Aged , Brain Ischemia/diagnosis , Brain Ischemia/etiology , Female , Fibrinolytic Agents/administration & dosage , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Treatment Outcome
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