Transient receptor potential melastatin 7 (TRPM7) is an ion channel that mediates monovalent cations out of cells, as well as the entry of divalent cations, such as zinc, magnesium, and calcium, into the cell. It has been reported that inhibitors of TRPM7 are neuroprotective in various neurological diseases. Previous studies in our lab suggested that seizure-induced neuronal death may be caused by the excessive release of vesicular zinc and the subsequent accumulation of zinc in the neurons. However, no studies have evaluated the effects of carvacrol and 2-aminoethoxydiphenyl borate (2-APB), both inhibitors of TRPM7, on the accumulation of intracellular zinc in dying neurons following seizure. Here, we investigated the therapeutic efficacy of carvacrol and 2-APB against pilocarpine-induced seizure. Carvacrol (50 mg/kg) was injected once per day for 3 or 7 days after seizure. 2-APB (2 mg/kg) was also injected once per day for 3 days after seizure. We found that inhibitors of TRPM7 reduced seizure-induced TRPM7 overexpression, intracellular zinc accumulation, and reactive oxygen species production. Moreover, there was a suppression of oxidative stress, glial activation, and the blood–brain barrier breakdown. In addition, inhibitors of TRPM7 remarkably decreased apoptotic neuron death following seizure. Taken together, the present study demonstrates that TRPM7-mediated zinc translocation is involved in neuron death after seizure. The present study suggests that inhibitors of TRPM7 may have high therapeutic potential to reduce seizure-induced neuron death.

A variety of pathogenic mechanisms, such as cytoplasmic calcium/zinc influx, reactive oxygen species production, and ionic imbalance, have been suggested to play a role in cerebral ischemia induced neurodegeneration. During the ischemic state that occurs after stroke or heart attack, it is observed that vesicular zinc can be released into the synaptic cleft, and then translocated into the cytoplasm via various cation channels. Transient receptor potential melastatin 2 (TRPM2) is highly distributed in the central nervous system and has high sensitivity to oxidative damage. Several previous studies have shown that TRPM2 channel activation contributes to neuroinflammation and neurodegeneration cascades. Therefore, we examined whether anti-oxidant treatment, such as with N-acetyl-l-cysteine (NAC), provides neuroprotection via regulation of TRPM2, following global cerebral ischemia (GCI). Experimental animals were then immediately injected with NAC (150 mg/kg/day) for 3 and 7 days, before sacrifice. We demonstrated that NAC administration reduced activation of GCI-induced neuronal death cascades, such as lipid peroxidation, microglia and astroglia activation, free zinc accumulation, and TRPM2 over-activation. Therefore, modulation of the TRPM2 channel can be a potential therapeutic target to prevent ischemia-induced neuronal death.

Epilepsy is one of the most common and severe brain diseases. The exact cause of epilepsy is unclear. Epilepsy often occurs following brain damage, such as traumatic brain injury (TBI) and ischemia. Cerebrolysin is a porcine brain peptide that is a unique neurotropic and neuroprotective agent. Cerebrolysin has been reported to increase neuroprotective effects after TBI, ischemia, and other CNS diseases. However, the effects of cerebrolysin on seizures are not known. Therefore, this study aimed to investigate the effects of neuropeptide cerebrolysin on neuronal death in the hippocampus after a seizure. To confirm the effects of cerebrolysin, we used a pilocarpine-induced seizure animal model. Cerebrolysin (2.5 ml/kg, i.p., once per day for 7 days) was immediately injected after a seizure induction. After 1 week, we obtained brain tissues and performed staining to histologically evaluate the potentially protective effects of cerebrolysin on seizure-induced neuronal death in the hippocampus. We found that cerebrolysin decreased hippocampal neuronal death after a seizure. In addition, an increase in brain-derived neurotrophic factor (BDNF) was confirmed through Western blot analysis to further support our hypothesis. Therefore, the present study suggests that the administration of cerebrolysin can be a useful therapeutic tool for preventing neuronal death after a seizure.

Although there have been substantial advances in knowledge regarding the mechanisms of neuron death after stroke, effective therapeutic measures for stroke are still insufficient. Excitatory amino acid carrier 1 (EAAC1) is a type of neuronal glutamate transporter and considered to have an additional action involving the neuronal uptake of cysteine, which acts as a crucial substrate for glutathione synthesis. Previously, our lab demonstrated that genetic deletion of EAAC1 leads to decreased neuronal glutathione synthesis, increased oxidative stress, and subsequent cognitive impairment. Therefore, we hypothesized that reduced neuronal transport of cysteine due to deletion of the EAAC1 gene might exacerbate neuronal injury and impair adult neurogenesis in the hippocampus after transient cerebral ischemia. EAAC1 gene deletion profoundly increased ischemia-induced neuronal death by decreasing the antioxidant capacity. In addition, genetic deletion of EAAC1 also decreased the overall neurogenesis processes, such as cell proliferation, differentiation, and survival, after cerebral ischemia. These studies strongly support our hypothesis that EAAC1 is crucial for the survival of newly generated neurons, as well as mature neurons, in both physiological and pathological conditions. Here, we present a comprehensive review of the role of EAAC1 in neuronal death and neurogenesis induced by ischemic stroke, focusing on its potential cellular and molecular mechanisms.

Thus far, few studies have compared the effects of sugammadex and cholinesterase inhibitors on postoperative nausea and vomiting (PONV), and the results have been controversial. Here, we compared the effects of sugammadex, neostigmine, and pyridostigmine on PONV by means of a five hospital analysis with propensity score matching. We analyzed adults aged ≥ 18 years who underwent general anesthesia between January 2014 and December 2019. Following propensity score matching, 7793 patients were included in each of the neostigmine and sugammadex matched patient groups (absolute standardized difference (ASD), 0.01–0.07), and 10,197 patients were included in each of the pyridostigmine and sugammadex matched patient groups (ASD, 0.01–0.02), while 19,377 patients were included in each of the pyridostigmine and neostigmine matched patient groups. (ASD, 0.01–0.19). The odds of PONV were low in the sugammadex group (odds ratio, 0.65; 95% confidence interval, 0.59–0.72; p < 0.0001) and pyridostigmine group (odds ratio, 0.22; 95% confidence interval, 0.20–0.24; p < 0.0001) compared to the neostigmine group, while there was no difference between sugammadex and pyridostigmine (odds ratio, 0.95; 95% confidence interval, 0.86–1.04; p = 0.281). Therefore, sugammadex and pyridostigmine may lower the incidence of PONV compared to neostigmine in patients undergoing general anesthesia.

The impact of migraine on postoperative nausea and vomiting (PONV) is controversial, and few studies have focused on their relationship. Thus, we investigated the impact of migraine, among other risk factors, on PONV in a large retrospective study. We analyzed 10 years of clinical data from the Smart Clinical Data Warehouse of Hallym University Medical Center. PONV was defined as nausea or vomiting within the first 24 h after surgery. Patients diagnosed by a neurologist and with a history of triptan use before surgery were enrolled into the migraine group. We enrolled 208,029 patients aged > 18 years who underwent general anesthesia (GA), among whom 19,786 developed PONV within 24 h after GA and 1982 had migraine. Before propensity score matching, the unadjusted and fully adjusted odds ratios (ORs) for PONV in subjects with versus without migraine were 1.52 (95% confidence interval (CI), 1.34–1.72; p < 0.001) and 1.37 (95% CI, 1.21–1.56; p < 0.001), respectively. The OR for PONV in patients with migraine was also high (OR, 1.37; 95% CI, 1.13–1.66; p = 0.001) after matching. Our findings suggest that migraine is a significant risk factor for PONV.