Human neuroblastoma SH-SY5Y cells are a widely-used human neuronal cell model in the study of neurodegeneration. A recent study shows that, 1-methyl-4-phenylpyridine ion (MPP), which selectively causes dopaminergic neuronal death leading to Parkinson’s disease-like symptoms, can reduce SH-SY5Y cell viability by inducing H2O2 generation and subsequent TRPM2 channel activation. MPP-induced cell death is enhanced by increasing the TRPM2 expression. By contrast, increasing the TRPM2 expression has also been reported to support SH-SY5Y cell survival after exposure to H2O2, leading to the suggestion of a protective role for the TRPM2 channel. To clarify the role of reactive oxygen species (ROS)-induced TRPM2 channel activation in SH-SY5Y cells, we generated a stable SH-SY5Y cell line overexpressing the human TRPM2 channel and examined cell death and cell viability after exposure to H2O2 in the wild-type and TRPM2-overexpressing SH-SY5Y cells. Exposure to H2O2 resulted in concentration-dependent cell death and reduction in cell viability in both cell types. TRPM2 overexpression remarkably augmented H2O2-induced cell death and reduction in cell viability. Furthermore, H2O2-induced cell death in both the wild-type and TRPM2-overexpressing cells was prevented by 2-APB, a TRPM2 inhibitor, and also by PJ34 and DPQ, poly(ADP-ribose) polymerase (PARP) inhibitors. Collectively, our results show that increasing the TRPM2 expression renders SH-SY5Y cells to be more susceptible to ROS-induced cell death and reinforce the notion that the TRPM2 channel plays a critical role in conferring ROS-induced cell death. It is anticipated that SH-SY5Y cells can be useful for better understanding the molecular and signaling mechanisms for ROS-induced TRPM2-mediated neurodegeneration in the pathogenesis of neurodegenerative diseases.

The transient receptor potential melastatin‐related 2 (TRPM2) channel, a reactive oxygen species (ROS)‐sensitive cation channel, has been well recognized for being an important and common mechanism that confers the susceptibility to ROS‐induced cell death. An elevated level of ROS is a salient feature of ischaemia‐reperfusion, chronic cerebral hypo‐perfusion and neonatal hypoxia‐ischaemia. The TRPM2 channel is expressed in hippocampus, cortex and striatum, the brain regions that are critical for cognitive functions. In this review, we examine the recent studies that combine pharmacological and/or genetic interventions with using in vitro and in vivo models to demonstrate a crucial role of the TRPM2 channel in brain damage by ischaemia‐reperfusion, chronic cerebral hypo‐perfusion and neonatal hypoxic‐ischaemia. We also discuss the current understanding of the underlying TRPM2‐dependent cellular and molecular mechanisms. These new findings lead to the hypothesis of targeting the TRPM2 channel as a potential novel therapeutic strategy to alleviate brain damage and cognitive dysfunction caused by these conditions.

Gasdermin D-executing pyroptosis mediated by NLRP3 inflammasomes has been recognized as a key pathogenesis during stroke. Hydrogen sulfide (H2S) could protect CNS against ischemia/reperfusion (I/R)-induced neuroinflammation, while the underlying mechanism remains unclear. The study applied the middle cerebral artery occlusion/reperfusion (MCAO/R) model to investigate how the brain and the retinal injuries were alleviated in sodium hydrogen sulfide (NaHS)-treated rats. The rats were assigned to four groups and received an intraperitoneal injection of 50 μmol/kg NaHS or NaCl 15 min after surgery. Neurological deficits were evaluated using the modified neurologic severity score. The quantification of pro-inflammatory cytokines, NLRP3, caspase-1, and GSDMD were determined by ELISA and Western blot. Cortical and retinal neurodegeneration and cell pyroptosis were determined by histopathologic examination. Results showed that NaHS rescued post-stroke neurological deficits and infarct progression, improved retina injury, and attenuated neuroinflammation in the brain cortexes and the retinae. NaHS administration inhibits inflammation by blocking the NLRP3/caspase-1/GSDMD pathway and further suppressing neuronal pyroptosis. This is supported by the fact that it reversed the high-level of NLRP3, caspase-1, and GSDMD following I/R. Our findings suggest that compounds with the ability to donate H2S could constitute a novel therapeutic strategy for ischemic stroke.

Objective In order to determine research hotspots and prospective directions, this work used VOSviewer and CiteSpace to assess the current state of insular epilepsy research. Methods We looked for pertinent research about insular epilepsy published between the first of January 2000 and the thirtieth of April 2022 in the Web of Science Core Collection (WoSCC) database. CiteSpace and VOSviewer were used to build a knowledge atlas by analyzing authors, institutions, countries, keywords with citation bursts, keyword clustering, keyword co-occurrence, publishing journals, reference co-citation patterns, and other factors. Results A total of 305 publications on insular epilepsy were found. Nguyen DK had the most articles published (37), whereas Mauguière F and Isnard J had the highest average number of citations/publications (39.37 and 38.09, respectively). The leading countries and institutions in this field were the United States (82 papers) and Université de Montréal (40 papers). Authors, countries, and institutions appear to be actively collaborating. Hot topics and research frontiers included surgical treatment, functional network connectivity, and the application of neuroimaging methods to study insular epilepsy. Conclusion In summary, the most influential articles, authors, journals, organizations, and countries on the subject of insular epilepsy were determined by this analysis. This study investigated the area of insular epilepsy research and forecasted upcoming trends using co-occurrence and evolution methods.