Many types of plastic products,including polystyrene,have long been used in commercial and industrial applications.Microplastics and nanoplastics,plastic particles derived from these plastic products,are emerging as e...Many types of plastic products,including polystyrene,have long been used in commercial and industrial applications.Microplastics and nanoplastics,plastic particles derived from these plastic products,are emerging as environmental pollutants that can pose health risks to a wide variety of living organisms,including humans.However,it is not well understood how microplastics and nanoplastics affect cellular functions and induce stress responses.Humans can be exposed to polystyrene-microplastics and polystyrene-nanoplastics through ingestion,inhalation,or skin contact.Most ingested plastics are excreted from the body,but inhaled plastics may accumulate in the lungs and can even reach the brain via the nose-to-brain route.Small-sized polystyrene-nanoplastics can enter cells by endocytosis,accumulate in the cytoplasm,and cause various cellular stresses,such as inflammation with increased pro-inflammatory cytokine production,oxidative stress with generation of reactive oxygen species,and mitochondrial dysfunction.They induce autophagy activation and autophagosome formation,but autophagic flux may be impaired due to lysosomal dysfunction.Unless permanently exposed to polystyrene-nanoplastics,they can be removed from cells by exocytosis and subsequently restore cellular function.However,neurons are very susceptible to this type of stress,thus even acute exposure can lead to neurodegeneration without recovery.This review focuses specifically on recent advances in research on polystyrene-nanoplastic-induced cytotoxicity and neurotoxicity.Furthermore,in this review,based on mechanistic studies of polystyrene-nanoplastics at the cellular level other than neurons,future directions for overcoming the negative effects of polystyrene-nanoplastics on neurons were suggested.展开更多
Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic effects.Central toxicity induced by psychostimulants may pose serio...Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic effects.Central toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and adults.The present review provides an overview of recent research,conducted between 2018 and 2023,focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine,cocaine,methamphetamine,3,4-methylenedioxymethamphetamine,methylphenidate,caffeine,and nicotine.Detailed elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes.展开更多
Aconitine,a common and main toxic component of Aconitum,is toxic to the central nervous system.However,the mechanism of aconitine neurotoxicity is not yet clear.In this work,we had the hypothesis that excitatory amino...Aconitine,a common and main toxic component of Aconitum,is toxic to the central nervous system.However,the mechanism of aconitine neurotoxicity is not yet clear.In this work,we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine.HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system.Meanwhile,to confirm the metabolic mechanism of aconitine toxicity on HT22 cells,the levels of lactate dehydrogenase,intracellular Ca^(2+),reactive oxygen species,glutathione and superoxide dismutase,and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology.Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid,which was followed by the accumulation of lactic acid and reduction of glucose.The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca^(2+)overload and oxidative stress,and eventually result in cell apoptosis.In general,we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.展开更多
Objectives: To use a novel in vitro model of three-dimensional(3D) neurosphere cultures to assess neurotoxic or neuroprotective effects with harmane as a model compound.Methods: A reproducible model of 3D spheroids wa...Objectives: To use a novel in vitro model of three-dimensional(3D) neurosphere cultures to assess neurotoxic or neuroprotective effects with harmane as a model compound.Methods: A reproducible model of 3D spheroids was developed from embryonic mouse cortical neurons,using molded agarose micro-wells;this method seems particularly practical as it is customizable and widely available and does not require specific cell treatments or assay components different from 2D cultures, allowing for the easy transposition of routine protocols. To assess the neurotoxic effects of harmane, a resazurin assay was performed to measure cell viability, and a highly sensitive fluorometric method, based on the oxidation of dichlorodihydrofluorescein, was applied to measure eventually induced reactive oxygen species(ROS) after exposure to harmane at increasing concentrations of 50 100,and 250 μm.Results: Hydrogel microwells facilitated the assembly of spheroids containing neurons and glial cells into a complex 3D structure and prevented the agglomeration of spheroids. Exposure to harmane induced cytotoxicity in 3D neural spheroids, which was correlated with harmane concentrations, with a 27%reduction in viability at 250 μm. Harmane that did not induce significant levels of oxidative stress was detected for all tested concentrations.Conclusion: This 3D neurosphere model mimics a neuronal microenvironment, allowing a fine study of neurodegenerative disorders and the effects of chemicals on the brain. This model opens novel opportunities, not only from a pathogenetic point of view but also from a therapeutic perspective.展开更多
Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse eff...Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.展开更多
Patients treated with platinum-based chemotherapy frequently experience neurotoxic symptoms, which may lead to premature discontinuation of therapy. Despitediscontinuation of platinum drugs, these symptoms can persist...Patients treated with platinum-based chemotherapy frequently experience neurotoxic symptoms, which may lead to premature discontinuation of therapy. Despitediscontinuation of platinum drugs, these symptoms can persist over a long period of time. Cisplatin and oxaliplatin, among all platinum drugs, have significant neurotoxic potential. A distal dose-dependent symmetrical sensory neuropathy is the most common presentation of platinum neurotoxicity. DNA damage-induced apoptosis of dorsal root ganglion(DRG) neurons seems to be the principal cause of neurological symptoms. However, DRG injury alone cannot explain some unique symptoms such as cold-aggravated burning pain affecting distal extremities that is observed with oxaliplatin administration. In this article, we briefly reviewed potential mechanisms for the development of platinum drugs-associated neurological manifestations.展开更多
Neurotoxicity is an infrequent adverse reaction to iodinated contrast agents. Contrast induced neurotoxicity following coronary angiogram is very rare. Renal disease is a risk factor for contrast induced neurotoxicity...Neurotoxicity is an infrequent adverse reaction to iodinated contrast agents. Contrast induced neurotoxicity following coronary angiogram is very rare. Renal disease is a risk factor for contrast induced neurotoxicity. We report a case of contrast induced neurotoxicity following coronary angiogram and intervention using Iohexol(Omnipaque 350) in an end stage renal disease patient on peritoneal dialysis who had prior exposure to iodinated contrast without any adverse reaction. Hemodialysis had to be initiated for rapid removal of the contrast agent with subsequent complete resolution of neurological deficits. This case highlights the need for interventionalists to be aware of an important adverse reaction to iodinated contrast agents, especially in individuals with renal dysfunction, and that neurotoxicity is a possibility even with prior uneventful exposures. The role and timing of hemodialysis in contrast induced neurotoxicity in patients with chronic kidney disease and in those without chronic kidney disease needs further deliberation.展开更多
Methamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson's disease. However,...Methamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson's disease. However, its specific mechanism of action is still unclear. In the present study, we established a Parkinson's disease pathology model by exposing SH-SY5 Y cells and C57 BL/6 J mice to methamphetamine. In vitro experiments were performed with 0, 0.5, 1.0, 1.5, 2.0 or 2.5 mM methamphetamine for 24 hours or 2.0 mM methamphetamine for 0-, 2-, 4-, 8-, 16-, and 24-hour culture of SH-SY5 Y cells. Additional experimental groups of SH-SY5 Y cells were administered a nitric oxide inhibitor, 0.1 mM N-nitro-L-arginine, 1 hour before exposure to 2.0 mM methamphetamine for 24 hours. In vivo experiments: C57 BL/6 J mice were intraperitoneally injected with N-nitro-L-arginine(8 mg/kg), eight times, at intervals of 12 hours. Methamphetamine 15 mg/kg was intraperitoneally injected eight times, at intervals of 12 hours, but 0.5-hour after each N-nitro-L-arginine injection in the combined group. Western blot assay was used to determine the expression of nitric oxide synthase, α-synuclein(α-Syn), 5 G4, nitrated α-synuclein at the residue Tyr39(nT39 α-Syn), cleaved caspase-3, and cleaved poly ADP-ribose polymerase(PARP) in cells and mouse brain tissue. Immunofluorescence staining was conducted to measure the positive reaction of NeuN, nT39 α-Syn and 5 G4. Enzyme linked immunosorbent assay was performed to determine the dopamine levels in the mouse brain. After methamphetamine exposure, α-Syn expression increased; the aggregation of α-Syn 5 G4 increased; nT39 α-Syn, nitric oxide synthase, cleaved caspase-3, and cleaved PARP expression increased in the cultures of SH-SY5 Y cells and in the brains of C57 BL/6 J mice; and dopamine levels were reduced in the mouse brain. These changes were markedly reduced when N-nitro-L-arginine was administered with methamphetamine in both SH-SY5 Y cells and C57 BL/6 J mice. These results suggest that nT39 α-Syn aggregation is involved in methamphetamine neurotoxicity.展开更多
Ghrelin is a neuropeptide that has various physiological functions and has been demonstrated to be neuroprotective in a number of neurological disease models.However,the underlying mechanisms of ghrelin in Parkinson’...Ghrelin is a neuropeptide that has various physiological functions and has been demonstrated to be neuroprotective in a number of neurological disease models.However,the underlying mechanisms of ghrelin in Parkinson’s disease remain largely unexplored.The current study aimed to study the effects of ghrelin in a 6-hydroxydopamine(6-OHDA)-induced Parkinson’s disease model and evaluate the potential underlying mechanisms.In the present study,we treated an SH-SY5 Y cell model with 6-OHDA,and observed that pretreatment with different concentrations of ghrelin(1,10,and 100 nM)for 30 minutes relieved the neurotoxic effects of 6-OHDA,as revealed by Cell Counting Kit-8 and Annexin V/propidium iodide(PI)apoptosis assays.Reverse transcription quantitative polymerase chain reaction and western blot assay results demonstrated that 6-OHDA treatment upregulatedα-synuclein and lincRNA-p21 and downregulated TG-interacting factor 1(TGIF1),which was predicted as a potential transcription regulator of the gene encodingα-synuclein(SNCA).Ghrelin pretreatment was able to reverse the trends caused by 6-OHDA.The Annexin V/PI apoptosis assay results revealed that inhibiting eitherα-synuclein or lincRNA-p21 expression with small interfering RNA(siRNA)relieved 6-OHDA-induced cell apoptosis.Furthermore,inhibiting lincRNA-p21 also partially upregulated TGIF1.By retrieving information from a bioinformatics database and performing both double luciferase and RNA immunoprecipitation assays,we found that lincRNA-p21 and TGIF1 were able to form a double-stranded RNA-binding protein Staufen homolog 1(STAU1)binding site and further activate the STAU1-mediated mRNA decay pathway.In addition,TGIF1 was able to transcriptionally regulateα-synuclein expression by binding to the promoter of SNCA.The Annexin V/PI apoptosis assay results showed that either knockdown of TGIF1 or overexpression of lincRNA-p21 notably abolished the neuroprotective effects of ghrelin against 6-OHDA-induced neurotoxicity.Collectively,these findings suggest that ghrelin exerts neuroprotective effects against 6-OHDA-induced neurotoxicity via the lincRNA-p21/TGIF1/α-synuclein pathway.展开更多
We report here the synthesis and in vivo anticonvulsant/neurotoxicity activities of a series of compounds belonging to 2-aryl-4-arylidene-1-phenyl-1H-imidazol-5(4H)-one. The scaffold is based on the commonality of 5-m...We report here the synthesis and in vivo anticonvulsant/neurotoxicity activities of a series of compounds belonging to 2-aryl-4-arylidene-1-phenyl-1H-imidazol-5(4H)-one. The scaffold is based on the commonality of 5-membered lactam ring structures as successful anticonvulsant agents. The present compounds exhibited a range of anticonvulsant activity in pentylenetetrazole (PTZ)-induced seizure test. In particular, the protection was excellent by compounds bearing furylmethylidene on C4, possibly due to good pharmacokinetic properties. It was found that high lipophilicity and/or electron deficient aryl ring substitution at C4 compromised the anticonvulsant activities. For example, chloro analogues were found much less active than unsubstituted phenyl or furyl derivatives. Regarding side effects, active compounds exerted no observable neurotoxic effect at their therapeutic doses in Chimney test.展开更多
The aim of this study was to investigate the potential protective effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, on glutama...The aim of this study was to investigate the potential protective effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, on glutamate-induced neurotoxicity in mice and its possible mechanism. Mice, except for controls, received simultaneously intragastric (ig) administration of monosodium glutamate [MSG, 4.0 g/(kg·d)] or/and intraperitoneal (ip) administration of TMP [10, 20, 40 mg/(kg·d)] for 10 d, and then behavioral tests, as well as histopathological and immunohistochemical examination of hippocampi were performed to analyze the glutamate-induced functional and morphological changes and the possible protective effect of TMP. The results showed that ip administration of TMP countered the effects of ig administration of MSG on behavior and histopathology, suggesting that TMP was a neuroprotective agent. This study provides evidence that TMP possesses obviously neuroprotection against glutamate-induced neurotoxicity, and the neuroprotection effect may result from its inhibiting expression of NMDARs, consequently blocking-up Ca2+ influx through the receptor’s associated ion channel, which can be neurotoxic.展开更多
Background: The aim of the present study was to evaluate the neuroprotective effect of allantoin in cisplatin‐induced toxicity in rats. Methods: Adult male Wistar rats weighing 160‐200 g were used. Neuropathy was in...Background: The aim of the present study was to evaluate the neuroprotective effect of allantoin in cisplatin‐induced toxicity in rats. Methods: Adult male Wistar rats weighing 160‐200 g were used. Neuropathy was induced by injecting cisplatin (2 mg/kg, ip, twice a week for 6 weeks) and the rats were concurrently treated with allantoin (200 and 400 mg/kg, po) for 8 weeks. At the end of the study, body weight and hemogram were measured. Behavioural tests were performed, including tests for cold and hot hyperalgesia, motor co‐ordination, locomotor activity, mechano‐tactile allodynia and mechanical hyperalgesia. The rats were then sacrificed and sciatic nerve conduction velocity was determined. The antioxidant enzyme and nitric oxide levels in sciatic nerve homogenates were measured. Results: In this study, allantoin restored the motor nerve conduction velocity deficits induced by cisplatin, and the allantoin‐treated rats showed improvement in cold and thermal hyperalgesia, mechano‐tactile allodynia, and mechanical hyperalgesia. Allantoin treatment also improved the rats’ hematological status, increasing haemoglobin, platelet and RBC counts compared to the cisplatin‐treated group. Allantoin treatment also mitigated the functional abnormalities seen in the cisplatin neuropathy group, protecting neurons from the neurotoxic effects of cisplatin. Conclusion: Allantoin shows promise for use as an adjuvant drug in cancer treatment to protect against cisplatin‐induced neuropathy.展开更多
We would like to comment on the interesting case report of lithium intoxication reported by Jing Peng.[1]An 18-year old female with mania developed confusion,trembling extremities,slurred speech,increased muscle tensi...We would like to comment on the interesting case report of lithium intoxication reported by Jing Peng.[1]An 18-year old female with mania developed confusion,trembling extremities,slurred speech,increased muscle tension,and hyperactive tendon reflexes 20 days after initiating treatment with routine dosages of lithium bicarbonate.When admitted to the hospital due to her acute neurological condition,her serum lithium concentration was in the therapeutic range(0.57 mmol/L).Most of her symptoms spontaneously reversed one展开更多
Patients with colorectal cancer (CRC) can have chemotherapy with oxaliplatin postoperatively. Oxaliplatin can cause acute and chronic neurotoxicity. It is important to be aware of neurotoxic side effects so they can b...Patients with colorectal cancer (CRC) can have chemotherapy with oxaliplatin postoperatively. Oxaliplatin can cause acute and chronic neurotoxicity. It is important to be aware of neurotoxic side effects so they can be documented and action taken at an early stage. The study aimed to identify and explore neurotoxic side effects documented in the medical records of patients with colorectal cancer treated with oxaliplatin-based adjuvant chemotherapy. Data in this study were medical records;presenting documentation about patients treated at the University Hospital in the south of Sweden between 2009 and 2010. A summative content analysis approach was used to explore the neurotoxic side effects. Identification and quantification of the content of medical records were carried out by using a study-specific protocol. “Cold sensitivity” and “tingling in the hands” were the most frequently documented neurotoxicity-related terms in the medical records. This identification was followed by interpretation. Three categories were identified in the interpretive part of the study: acute, chronic, and degree of neurotoxicity. The results show the importance of awareness of neurotoxic side effects so that they can be documented and action taken at an early stage. The documentation could be more reliable if patient-reported structured measurements were used, combined with free descriptions in the medical records. Being able to follow the progression of the symptoms during and after treatment would improve patient’s safety and also quality of life. The protocol that we developed and used in this review of medical records may be helpful to structure the documentation in the electronic system for documentation of neurotoxicity side effects.展开更多
Objective: To evaluate the neuroprotective effect of ashwagandha extract against aluminum chloride-induced neurotoxicity in rats. Methods: Rats were divided into control, aluminumintoxicated rats treated daily with al...Objective: To evaluate the neuroprotective effect of ashwagandha extract against aluminum chloride-induced neurotoxicity in rats. Methods: Rats were divided into control, aluminumintoxicated rats treated daily with aluminum trichloride(Al Cl3)(100 mg/kg, orally) for 30 d and aluminum-intoxicated animals protected by receiving daily ashwagandha extract(200 mg/kg, orally) one hour before Al Cl3 administration for 30 d. Levels of lipid peroxidation, nitric oxide, reduced glutathione and tumor necrosis factor-α were measured in the cortex, hippocampus and striatum. In addition, the activities of Na+, K+, ATPase and acetylcholinesterase were determined in the three studied brain regions. Results: Aluminum increased the levels of lipid peroxidation and nitric oxide in the cortex, hippocampus and striatum and decreased the reduced glutathione level in the hippocampus and striatum. In rats protected with ashwagandha extract, non significant changes were observed in lipid peroxidation, nitric oxide and reduced glutathione. In addition, ashwagandha extracts prevented the increased activity of acetylcholinesterase and Na+, K+, ATPase induced by Al Cl3 in the cortex, hippocampus and striatum. The present findings also showed that the significant increase in tumor necrosis factor-α induced by Al Cl3 in the cortex and hippocampus was prevented by ashwagandha extract. Conclusions: The present results suggest that ashwagandha extract possesses antioxidant and anti-inflammatory effects against aluminum neurotoxicity. In addition, ashwagandha extract could prevent the decline in cholinergic activity by maintaining normal acetylcholinesterase activity. The later effect could recommend the use of ashwagandha as a memory enhancer.展开更多
OBJECTIVE Previously we demonstrated the neuroprotective effect of 5-lipoxygenase(5-LOX)inhibitor as well as cysteinyl leukotriene receptor 1(Cys LT1)antagoniston rotenone-induced microglial activation and neuronal de...OBJECTIVE Previously we demonstrated the neuroprotective effect of 5-lipoxygenase(5-LOX)inhibitor as well as cysteinyl leukotriene receptor 1(Cys LT1)antagoniston rotenone-induced microglial activation and neuronal death.In this study,we determined the effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast on neurotoxicity induced by 1-methyl-4-phenylpyridine(MPP+)in an in vitro model of Parkinson disease(PD).METHODS The neurotoxicity of MPP+,a neurotoxin relevant to PD,on the PC12 cells was measured by MTT assay,lactate dehydrogenase(LDH)release and double fluorescence staining with Hoechst/propidiumiodide(PI).The protective effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast were investigated by the above methods.RESULTS We found that exposure of PC12 cells to MPP+led to a reduced cell viability and an increased level of LDH in a concentration-dependent manner.Pretreatment with zileuton and montelukast significantly attenuated viability loss and LDH release in MPP+-treated PC12 cells.Furthermore,MPP+increasednecrotic cell death in PC12 cells.Administration of montelukast significantly decreased MPP+-induced cell necrosis in PC12 cells.CONCLUSION The 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast have a neuroprotective effects on MPP+-induced neurotoxicity in PC12 cells.The 5-LOX inhibitor and Cys LT1 antagonist might raise a possibility as potential therapeutic agent for PD and other inflammation-related the central nervous system disorders.展开更多
Our study investigated the neurotoxicity of quinolinic acid(QA) to spiral ganglion cells(SGCs),observed the protective effects of N-methyl-D-aspartate(NMDA) receptor antagonist MK-801 and magnesium ions on the QA-indu...Our study investigated the neurotoxicity of quinolinic acid(QA) to spiral ganglion cells(SGCs),observed the protective effects of N-methyl-D-aspartate(NMDA) receptor antagonist MK-801 and magnesium ions on the QA-induced injury to SGCs,and analyzed the role of QA in otitis media with effusion(OME)-induced sensorineural hearing loss(SNHL).After culture in vitro for 72 h,SGCs were exposed to different media and divided into 4 groups:the blank control group,the QA injury group,the MK-801 treatment group,and the MgCl2 protection group.The apoptosis rate of SGCs was analyzed by Annexin V and PI double staining under the fluorescence microscopy 24 h later.SGCs were cultured in vitro for 72 h and divided into four groups:the low concentration QA group,the high concentration QA group,the MK-801 group,the MgCl2 group.The transient changes of intracellular calcium concentration were observed by the laser scanning confocal microscopy.Apoptosis rate in QA injury group was higher than that in blank control group and MgCl2 protection group(both P<0.05),but there was no significant difference between MK-801 treatment group and blank control group(P>0.05).In high concentration QA group,there was an obvious increase of the intracellular calcium concentration in SGCs,which didn't present in low concentration QA group.In MgCl2 group,the peak values of the intracellular calcium concentration in SGCs were reduced and the duration was shortened,but the intracellular calcium concentration in SGCs had no significant change in MK-801 group.It was concluded that QA could injure SGCs by excessively activating NMDA receptors on the cell membrane,which might be the mechanism by which OME induced SNHL,while Mg2+ could protect the SCGs from the neurotoxicity of QA.展开更多
Dopaminergic neurotoxicity is characterized by damage and death of dopaminergic neurons.Parkinson's disease(PD)is a neurodegenerative disorder that primarily involves the loss of dopaminergic neurons in the substa...Dopaminergic neurotoxicity is characterized by damage and death of dopaminergic neurons.Parkinson's disease(PD)is a neurodegenerative disorder that primarily involves the loss of dopaminergic neurons in the substantia nigra.Therefore,the study of the mechanisms,as well as the search for new targets for the prevention and treatment of neurodegenerative diseases,is an important focus of modern neuroscience.PD is primarily caused by dysfunction of dopaminergic neurons;however,other neurotransmitter systems are also involved.Research reports have indicated that the glutamatergic system is involved in different pathological conditions,including dopaminergic neurotoxicity.Over the last two decades,the important functional interplay between dopaminergic and glutamatergic systems has stimulated interest in the possible role of metabotropic glutamate receptors(mGluRs)in the development of extrapyramidal disorders.However,the specific mechanisms driving these processes are presently unclear.The participation of the universal neuronal messenger nitric oxide(NO)in the mechanisms of dopaminergic neurotoxicity has attracted increased attention.The current paper aims to review the involvement of mGluRs and the contribution of NO to dopaminergic neurotoxicity.More precisely,we focused on studies conducted on the rotenone-induced PD model.This review is also an outline of our own results obtained using the method of electron paramagnetic resonance,which allows quantitation of NO radicals in brain structures.展开更多
Alzheimer disease is one of the commonest neurological diseases which is characterized by amyloid plaques accumulation in multiple brain regions. This study investigated the potential neuroprotective effect of artesun...Alzheimer disease is one of the commonest neurological diseases which is characterized by amyloid plaques accumulation in multiple brain regions. This study investigated the potential neuroprotective effect of artesunate on aluminum induced neurotoxicity vs memantine in rats. 40 male albino Wistar rats were divided randomly into 4 groups as follow: Group 1 negative control, group 2 positive control group induced by ammonium chloride, group 3 rats treated by NH4Cl + artesunate solution, group 4 rats treated by NH4Cl + memantine S.C. spatial Memory and Learning were evaluated using Morris Water Maze (MWM) test. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured in cerebral cortex tissue homogenate. Tumor necrosis factor-α (TNFα) and interleukin-1 beta (IL-1β) concentrations were measured in rat cerebral cortex tissue homogenate using rat enzyme linked immunosorbent assay (ELISA) kits. Real-time quantitative reverse transcription-polymerase chain reaction (Real-time qRT-PCR) for Caspase-3, Bcl-2 and iNOS gene expression was measured in rat cerebral cortex. Slices from cerebral cortex were studied by histopathological examination. Artesunate significantly decreased MDA level and inhibited iNOS, caspase and upregulated Bcl-2 gene expression in cerebral cortex. ART increased significantly antioxidant level GSH, and decreased significantly TNF-alpha and IL-B levels. It reduced significantly 1ry retention latency, 2ry retention latency and initial acquisition latency. It also improved brain histopathology and decreased amyloid plaque deposition. ART exerted neuroprotective effect through oxidative stress correction and enhancement of antiapoptotic markers in neuronal cells of the cerebral cortex.展开更多
Children are being exposed to an increasingly greater variety of anesthetics with advances in pediatric and obstetric surgery.Recent animal and retrospective human data suggest that the general anesthetics commonly us...Children are being exposed to an increasingly greater variety of anesthetics with advances in pediatric and obstetric surgery.Recent animal and retrospective human data suggest that the general anesthetics commonly used in pediatric medicine could be damaging to the developing brain when used at clinical concentrations.In vivo primate and rodent models have shown that neonatal exposure to clinical concentrations of anesthetics causes neural apoptosis展开更多
基金supported by the Basic Study and Interdisciplinary R&D Foundation of the University of Seoul(2019)grants,Nos.201910021035202006251003(both to KYR and JC)。
文摘Many types of plastic products,including polystyrene,have long been used in commercial and industrial applications.Microplastics and nanoplastics,plastic particles derived from these plastic products,are emerging as environmental pollutants that can pose health risks to a wide variety of living organisms,including humans.However,it is not well understood how microplastics and nanoplastics affect cellular functions and induce stress responses.Humans can be exposed to polystyrene-microplastics and polystyrene-nanoplastics through ingestion,inhalation,or skin contact.Most ingested plastics are excreted from the body,but inhaled plastics may accumulate in the lungs and can even reach the brain via the nose-to-brain route.Small-sized polystyrene-nanoplastics can enter cells by endocytosis,accumulate in the cytoplasm,and cause various cellular stresses,such as inflammation with increased pro-inflammatory cytokine production,oxidative stress with generation of reactive oxygen species,and mitochondrial dysfunction.They induce autophagy activation and autophagosome formation,but autophagic flux may be impaired due to lysosomal dysfunction.Unless permanently exposed to polystyrene-nanoplastics,they can be removed from cells by exocytosis and subsequently restore cellular function.However,neurons are very susceptible to this type of stress,thus even acute exposure can lead to neurodegeneration without recovery.This review focuses specifically on recent advances in research on polystyrene-nanoplastic-induced cytotoxicity and neurotoxicity.Furthermore,in this review,based on mechanistic studies of polystyrene-nanoplastics at the cellular level other than neurons,future directions for overcoming the negative effects of polystyrene-nanoplastics on neurons were suggested.
基金supported by PON AIM(PON RICERCA E INNOVAZIONE 2014-2020,-AZIONE I.2.D.D.N.407 DEL 27 FEBBRAIO 2018-“ATTRACTION AND INTERNATIONAL MOBILITY”)(to GC)Zardi-Gori Foundation(research grant 2021)(to MS)+1 种基金intramural funds from the University of Cagliari(to NS)Fondazione CON IL SUD and The U.S.-Italy Fulbright Commission(to AEP).
文摘Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic effects.Central toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and adults.The present review provides an overview of recent research,conducted between 2018 and 2023,focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine,cocaine,methamphetamine,3,4-methylenedioxymethamphetamine,methylphenidate,caffeine,and nicotine.Detailed elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes.
基金supported the National Natural Science Foundation of China(Grant Nos.:81973569,82130113,and 22034005)the National Key R&D Program of China(Grant No.:2021YFF0600700)the“Xinglin Scholars”Research Promotion Program of Chengdu University of Traditional Chinese Medicine(Grant No.:BSH2021009).
文摘Aconitine,a common and main toxic component of Aconitum,is toxic to the central nervous system.However,the mechanism of aconitine neurotoxicity is not yet clear.In this work,we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine.HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system.Meanwhile,to confirm the metabolic mechanism of aconitine toxicity on HT22 cells,the levels of lactate dehydrogenase,intracellular Ca^(2+),reactive oxygen species,glutathione and superoxide dismutase,and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology.Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid,which was followed by the accumulation of lactic acid and reduction of glucose.The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca^(2+)overload and oxidative stress,and eventually result in cell apoptosis.In general,we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.
基金funded through a Fonds Medical pour la Recherche dans le Hainaut(FMRH)granta Kangaroo grant from the UMONS Health Institute.
文摘Objectives: To use a novel in vitro model of three-dimensional(3D) neurosphere cultures to assess neurotoxic or neuroprotective effects with harmane as a model compound.Methods: A reproducible model of 3D spheroids was developed from embryonic mouse cortical neurons,using molded agarose micro-wells;this method seems particularly practical as it is customizable and widely available and does not require specific cell treatments or assay components different from 2D cultures, allowing for the easy transposition of routine protocols. To assess the neurotoxic effects of harmane, a resazurin assay was performed to measure cell viability, and a highly sensitive fluorometric method, based on the oxidation of dichlorodihydrofluorescein, was applied to measure eventually induced reactive oxygen species(ROS) after exposure to harmane at increasing concentrations of 50 100,and 250 μm.Results: Hydrogel microwells facilitated the assembly of spheroids containing neurons and glial cells into a complex 3D structure and prevented the agglomeration of spheroids. Exposure to harmane induced cytotoxicity in 3D neural spheroids, which was correlated with harmane concentrations, with a 27%reduction in viability at 250 μm. Harmane that did not induce significant levels of oxidative stress was detected for all tested concentrations.Conclusion: This 3D neurosphere model mimics a neuronal microenvironment, allowing a fine study of neurodegenerative disorders and the effects of chemicals on the brain. This model opens novel opportunities, not only from a pathogenetic point of view but also from a therapeutic perspective.
文摘Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.
文摘Patients treated with platinum-based chemotherapy frequently experience neurotoxic symptoms, which may lead to premature discontinuation of therapy. Despitediscontinuation of platinum drugs, these symptoms can persist over a long period of time. Cisplatin and oxaliplatin, among all platinum drugs, have significant neurotoxic potential. A distal dose-dependent symmetrical sensory neuropathy is the most common presentation of platinum neurotoxicity. DNA damage-induced apoptosis of dorsal root ganglion(DRG) neurons seems to be the principal cause of neurological symptoms. However, DRG injury alone cannot explain some unique symptoms such as cold-aggravated burning pain affecting distal extremities that is observed with oxaliplatin administration. In this article, we briefly reviewed potential mechanisms for the development of platinum drugs-associated neurological manifestations.
文摘Neurotoxicity is an infrequent adverse reaction to iodinated contrast agents. Contrast induced neurotoxicity following coronary angiogram is very rare. Renal disease is a risk factor for contrast induced neurotoxicity. We report a case of contrast induced neurotoxicity following coronary angiogram and intervention using Iohexol(Omnipaque 350) in an end stage renal disease patient on peritoneal dialysis who had prior exposure to iodinated contrast without any adverse reaction. Hemodialysis had to be initiated for rapid removal of the contrast agent with subsequent complete resolution of neurological deficits. This case highlights the need for interventionalists to be aware of an important adverse reaction to iodinated contrast agents, especially in individuals with renal dysfunction, and that neurotoxicity is a possibility even with prior uneventful exposures. The role and timing of hemodialysis in contrast induced neurotoxicity in patients with chronic kidney disease and in those without chronic kidney disease needs further deliberation.
基金supported by the National Natural Science Foundation of China,No.81373240(to PMQ)and 81671865(to PMQ)
文摘Methamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson's disease. However, its specific mechanism of action is still unclear. In the present study, we established a Parkinson's disease pathology model by exposing SH-SY5 Y cells and C57 BL/6 J mice to methamphetamine. In vitro experiments were performed with 0, 0.5, 1.0, 1.5, 2.0 or 2.5 mM methamphetamine for 24 hours or 2.0 mM methamphetamine for 0-, 2-, 4-, 8-, 16-, and 24-hour culture of SH-SY5 Y cells. Additional experimental groups of SH-SY5 Y cells were administered a nitric oxide inhibitor, 0.1 mM N-nitro-L-arginine, 1 hour before exposure to 2.0 mM methamphetamine for 24 hours. In vivo experiments: C57 BL/6 J mice were intraperitoneally injected with N-nitro-L-arginine(8 mg/kg), eight times, at intervals of 12 hours. Methamphetamine 15 mg/kg was intraperitoneally injected eight times, at intervals of 12 hours, but 0.5-hour after each N-nitro-L-arginine injection in the combined group. Western blot assay was used to determine the expression of nitric oxide synthase, α-synuclein(α-Syn), 5 G4, nitrated α-synuclein at the residue Tyr39(nT39 α-Syn), cleaved caspase-3, and cleaved poly ADP-ribose polymerase(PARP) in cells and mouse brain tissue. Immunofluorescence staining was conducted to measure the positive reaction of NeuN, nT39 α-Syn and 5 G4. Enzyme linked immunosorbent assay was performed to determine the dopamine levels in the mouse brain. After methamphetamine exposure, α-Syn expression increased; the aggregation of α-Syn 5 G4 increased; nT39 α-Syn, nitric oxide synthase, cleaved caspase-3, and cleaved PARP expression increased in the cultures of SH-SY5 Y cells and in the brains of C57 BL/6 J mice; and dopamine levels were reduced in the mouse brain. These changes were markedly reduced when N-nitro-L-arginine was administered with methamphetamine in both SH-SY5 Y cells and C57 BL/6 J mice. These results suggest that nT39 α-Syn aggregation is involved in methamphetamine neurotoxicity.
基金supported by the National Natural Science Foundation of China,No.81901417(to XH)the Natural Science Foundation Doctoral Research Initiation Plan of Liaoning Province of China,No.2019-BS-287(to XH)the China Postdoctoral Science Foundation,No.2019M661173(to XH)。
文摘Ghrelin is a neuropeptide that has various physiological functions and has been demonstrated to be neuroprotective in a number of neurological disease models.However,the underlying mechanisms of ghrelin in Parkinson’s disease remain largely unexplored.The current study aimed to study the effects of ghrelin in a 6-hydroxydopamine(6-OHDA)-induced Parkinson’s disease model and evaluate the potential underlying mechanisms.In the present study,we treated an SH-SY5 Y cell model with 6-OHDA,and observed that pretreatment with different concentrations of ghrelin(1,10,and 100 nM)for 30 minutes relieved the neurotoxic effects of 6-OHDA,as revealed by Cell Counting Kit-8 and Annexin V/propidium iodide(PI)apoptosis assays.Reverse transcription quantitative polymerase chain reaction and western blot assay results demonstrated that 6-OHDA treatment upregulatedα-synuclein and lincRNA-p21 and downregulated TG-interacting factor 1(TGIF1),which was predicted as a potential transcription regulator of the gene encodingα-synuclein(SNCA).Ghrelin pretreatment was able to reverse the trends caused by 6-OHDA.The Annexin V/PI apoptosis assay results revealed that inhibiting eitherα-synuclein or lincRNA-p21 expression with small interfering RNA(siRNA)relieved 6-OHDA-induced cell apoptosis.Furthermore,inhibiting lincRNA-p21 also partially upregulated TGIF1.By retrieving information from a bioinformatics database and performing both double luciferase and RNA immunoprecipitation assays,we found that lincRNA-p21 and TGIF1 were able to form a double-stranded RNA-binding protein Staufen homolog 1(STAU1)binding site and further activate the STAU1-mediated mRNA decay pathway.In addition,TGIF1 was able to transcriptionally regulateα-synuclein expression by binding to the promoter of SNCA.The Annexin V/PI apoptosis assay results showed that either knockdown of TGIF1 or overexpression of lincRNA-p21 notably abolished the neuroprotective effects of ghrelin against 6-OHDA-induced neurotoxicity.Collectively,these findings suggest that ghrelin exerts neuroprotective effects against 6-OHDA-induced neurotoxicity via the lincRNA-p21/TGIF1/α-synuclein pathway.
文摘We report here the synthesis and in vivo anticonvulsant/neurotoxicity activities of a series of compounds belonging to 2-aryl-4-arylidene-1-phenyl-1H-imidazol-5(4H)-one. The scaffold is based on the commonality of 5-membered lactam ring structures as successful anticonvulsant agents. The present compounds exhibited a range of anticonvulsant activity in pentylenetetrazole (PTZ)-induced seizure test. In particular, the protection was excellent by compounds bearing furylmethylidene on C4, possibly due to good pharmacokinetic properties. It was found that high lipophilicity and/or electron deficient aryl ring substitution at C4 compromised the anticonvulsant activities. For example, chloro analogues were found much less active than unsubstituted phenyl or furyl derivatives. Regarding side effects, active compounds exerted no observable neurotoxic effect at their therapeutic doses in Chimney test.
文摘The aim of this study was to investigate the potential protective effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, on glutamate-induced neurotoxicity in mice and its possible mechanism. Mice, except for controls, received simultaneously intragastric (ig) administration of monosodium glutamate [MSG, 4.0 g/(kg·d)] or/and intraperitoneal (ip) administration of TMP [10, 20, 40 mg/(kg·d)] for 10 d, and then behavioral tests, as well as histopathological and immunohistochemical examination of hippocampi were performed to analyze the glutamate-induced functional and morphological changes and the possible protective effect of TMP. The results showed that ip administration of TMP countered the effects of ig administration of MSG on behavior and histopathology, suggesting that TMP was a neuroprotective agent. This study provides evidence that TMP possesses obviously neuroprotection against glutamate-induced neurotoxicity, and the neuroprotection effect may result from its inhibiting expression of NMDARs, consequently blocking-up Ca2+ influx through the receptor’s associated ion channel, which can be neurotoxic.
文摘Background: The aim of the present study was to evaluate the neuroprotective effect of allantoin in cisplatin‐induced toxicity in rats. Methods: Adult male Wistar rats weighing 160‐200 g were used. Neuropathy was induced by injecting cisplatin (2 mg/kg, ip, twice a week for 6 weeks) and the rats were concurrently treated with allantoin (200 and 400 mg/kg, po) for 8 weeks. At the end of the study, body weight and hemogram were measured. Behavioural tests were performed, including tests for cold and hot hyperalgesia, motor co‐ordination, locomotor activity, mechano‐tactile allodynia and mechanical hyperalgesia. The rats were then sacrificed and sciatic nerve conduction velocity was determined. The antioxidant enzyme and nitric oxide levels in sciatic nerve homogenates were measured. Results: In this study, allantoin restored the motor nerve conduction velocity deficits induced by cisplatin, and the allantoin‐treated rats showed improvement in cold and thermal hyperalgesia, mechano‐tactile allodynia, and mechanical hyperalgesia. Allantoin treatment also improved the rats’ hematological status, increasing haemoglobin, platelet and RBC counts compared to the cisplatin‐treated group. Allantoin treatment also mitigated the functional abnormalities seen in the cisplatin neuropathy group, protecting neurons from the neurotoxic effects of cisplatin. Conclusion: Allantoin shows promise for use as an adjuvant drug in cancer treatment to protect against cisplatin‐induced neuropathy.
文摘We would like to comment on the interesting case report of lithium intoxication reported by Jing Peng.[1]An 18-year old female with mania developed confusion,trembling extremities,slurred speech,increased muscle tension,and hyperactive tendon reflexes 20 days after initiating treatment with routine dosages of lithium bicarbonate.When admitted to the hospital due to her acute neurological condition,her serum lithium concentration was in the therapeutic range(0.57 mmol/L).Most of her symptoms spontaneously reversed one
基金Linköping University Hospital Swedish Society of Nursing
文摘Patients with colorectal cancer (CRC) can have chemotherapy with oxaliplatin postoperatively. Oxaliplatin can cause acute and chronic neurotoxicity. It is important to be aware of neurotoxic side effects so they can be documented and action taken at an early stage. The study aimed to identify and explore neurotoxic side effects documented in the medical records of patients with colorectal cancer treated with oxaliplatin-based adjuvant chemotherapy. Data in this study were medical records;presenting documentation about patients treated at the University Hospital in the south of Sweden between 2009 and 2010. A summative content analysis approach was used to explore the neurotoxic side effects. Identification and quantification of the content of medical records were carried out by using a study-specific protocol. “Cold sensitivity” and “tingling in the hands” were the most frequently documented neurotoxicity-related terms in the medical records. This identification was followed by interpretation. Three categories were identified in the interpretive part of the study: acute, chronic, and degree of neurotoxicity. The results show the importance of awareness of neurotoxic side effects so that they can be documented and action taken at an early stage. The documentation could be more reliable if patient-reported structured measurements were used, combined with free descriptions in the medical records. Being able to follow the progression of the symptoms during and after treatment would improve patient’s safety and also quality of life. The protocol that we developed and used in this review of medical records may be helpful to structure the documentation in the electronic system for documentation of neurotoxicity side effects.
文摘Objective: To evaluate the neuroprotective effect of ashwagandha extract against aluminum chloride-induced neurotoxicity in rats. Methods: Rats were divided into control, aluminumintoxicated rats treated daily with aluminum trichloride(Al Cl3)(100 mg/kg, orally) for 30 d and aluminum-intoxicated animals protected by receiving daily ashwagandha extract(200 mg/kg, orally) one hour before Al Cl3 administration for 30 d. Levels of lipid peroxidation, nitric oxide, reduced glutathione and tumor necrosis factor-α were measured in the cortex, hippocampus and striatum. In addition, the activities of Na+, K+, ATPase and acetylcholinesterase were determined in the three studied brain regions. Results: Aluminum increased the levels of lipid peroxidation and nitric oxide in the cortex, hippocampus and striatum and decreased the reduced glutathione level in the hippocampus and striatum. In rats protected with ashwagandha extract, non significant changes were observed in lipid peroxidation, nitric oxide and reduced glutathione. In addition, ashwagandha extracts prevented the increased activity of acetylcholinesterase and Na+, K+, ATPase induced by Al Cl3 in the cortex, hippocampus and striatum. The present findings also showed that the significant increase in tumor necrosis factor-α induced by Al Cl3 in the cortex and hippocampus was prevented by ashwagandha extract. Conclusions: The present results suggest that ashwagandha extract possesses antioxidant and anti-inflammatory effects against aluminum neurotoxicity. In addition, ashwagandha extract could prevent the decline in cholinergic activity by maintaining normal acetylcholinesterase activity. The later effect could recommend the use of ashwagandha as a memory enhancer.
基金The project supported National Natural Science Foundation of China(81273491)the Zhejiang Provincial Natural Science Foundation(LY12H31010)
文摘OBJECTIVE Previously we demonstrated the neuroprotective effect of 5-lipoxygenase(5-LOX)inhibitor as well as cysteinyl leukotriene receptor 1(Cys LT1)antagoniston rotenone-induced microglial activation and neuronal death.In this study,we determined the effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast on neurotoxicity induced by 1-methyl-4-phenylpyridine(MPP+)in an in vitro model of Parkinson disease(PD).METHODS The neurotoxicity of MPP+,a neurotoxin relevant to PD,on the PC12 cells was measured by MTT assay,lactate dehydrogenase(LDH)release and double fluorescence staining with Hoechst/propidiumiodide(PI).The protective effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast were investigated by the above methods.RESULTS We found that exposure of PC12 cells to MPP+led to a reduced cell viability and an increased level of LDH in a concentration-dependent manner.Pretreatment with zileuton and montelukast significantly attenuated viability loss and LDH release in MPP+-treated PC12 cells.Furthermore,MPP+increasednecrotic cell death in PC12 cells.Administration of montelukast significantly decreased MPP+-induced cell necrosis in PC12 cells.CONCLUSION The 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast have a neuroprotective effects on MPP+-induced neurotoxicity in PC12 cells.The 5-LOX inhibitor and Cys LT1 antagonist might raise a possibility as potential therapeutic agent for PD and other inflammation-related the central nervous system disorders.
基金supported by a grant from the National Natural Sciences Foundation of China (No.30872866)
文摘Our study investigated the neurotoxicity of quinolinic acid(QA) to spiral ganglion cells(SGCs),observed the protective effects of N-methyl-D-aspartate(NMDA) receptor antagonist MK-801 and magnesium ions on the QA-induced injury to SGCs,and analyzed the role of QA in otitis media with effusion(OME)-induced sensorineural hearing loss(SNHL).After culture in vitro for 72 h,SGCs were exposed to different media and divided into 4 groups:the blank control group,the QA injury group,the MK-801 treatment group,and the MgCl2 protection group.The apoptosis rate of SGCs was analyzed by Annexin V and PI double staining under the fluorescence microscopy 24 h later.SGCs were cultured in vitro for 72 h and divided into four groups:the low concentration QA group,the high concentration QA group,the MK-801 group,the MgCl2 group.The transient changes of intracellular calcium concentration were observed by the laser scanning confocal microscopy.Apoptosis rate in QA injury group was higher than that in blank control group and MgCl2 protection group(both P<0.05),but there was no significant difference between MK-801 treatment group and blank control group(P>0.05).In high concentration QA group,there was an obvious increase of the intracellular calcium concentration in SGCs,which didn't present in low concentration QA group.In MgCl2 group,the peak values of the intracellular calcium concentration in SGCs were reduced and the duration was shortened,but the intracellular calcium concentration in SGCs had no significant change in MK-801 group.It was concluded that QA could injure SGCs by excessively activating NMDA receptors on the cell membrane,which might be the mechanism by which OME induced SNHL,while Mg2+ could protect the SCGs from the neurotoxicity of QA.
文摘Dopaminergic neurotoxicity is characterized by damage and death of dopaminergic neurons.Parkinson's disease(PD)is a neurodegenerative disorder that primarily involves the loss of dopaminergic neurons in the substantia nigra.Therefore,the study of the mechanisms,as well as the search for new targets for the prevention and treatment of neurodegenerative diseases,is an important focus of modern neuroscience.PD is primarily caused by dysfunction of dopaminergic neurons;however,other neurotransmitter systems are also involved.Research reports have indicated that the glutamatergic system is involved in different pathological conditions,including dopaminergic neurotoxicity.Over the last two decades,the important functional interplay between dopaminergic and glutamatergic systems has stimulated interest in the possible role of metabotropic glutamate receptors(mGluRs)in the development of extrapyramidal disorders.However,the specific mechanisms driving these processes are presently unclear.The participation of the universal neuronal messenger nitric oxide(NO)in the mechanisms of dopaminergic neurotoxicity has attracted increased attention.The current paper aims to review the involvement of mGluRs and the contribution of NO to dopaminergic neurotoxicity.More precisely,we focused on studies conducted on the rotenone-induced PD model.This review is also an outline of our own results obtained using the method of electron paramagnetic resonance,which allows quantitation of NO radicals in brain structures.
文摘Alzheimer disease is one of the commonest neurological diseases which is characterized by amyloid plaques accumulation in multiple brain regions. This study investigated the potential neuroprotective effect of artesunate on aluminum induced neurotoxicity vs memantine in rats. 40 male albino Wistar rats were divided randomly into 4 groups as follow: Group 1 negative control, group 2 positive control group induced by ammonium chloride, group 3 rats treated by NH4Cl + artesunate solution, group 4 rats treated by NH4Cl + memantine S.C. spatial Memory and Learning were evaluated using Morris Water Maze (MWM) test. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured in cerebral cortex tissue homogenate. Tumor necrosis factor-α (TNFα) and interleukin-1 beta (IL-1β) concentrations were measured in rat cerebral cortex tissue homogenate using rat enzyme linked immunosorbent assay (ELISA) kits. Real-time quantitative reverse transcription-polymerase chain reaction (Real-time qRT-PCR) for Caspase-3, Bcl-2 and iNOS gene expression was measured in rat cerebral cortex. Slices from cerebral cortex were studied by histopathological examination. Artesunate significantly decreased MDA level and inhibited iNOS, caspase and upregulated Bcl-2 gene expression in cerebral cortex. ART increased significantly antioxidant level GSH, and decreased significantly TNF-alpha and IL-B levels. It reduced significantly 1ry retention latency, 2ry retention latency and initial acquisition latency. It also improved brain histopathology and decreased amyloid plaque deposition. ART exerted neuroprotective effect through oxidative stress correction and enhancement of antiapoptotic markers in neuronal cells of the cerebral cortex.
基金supported by the Japan Society for the Promotion of Science,Tokyo,JapanGrant No.23890054 and 25861361
文摘Children are being exposed to an increasingly greater variety of anesthetics with advances in pediatric and obstetric surgery.Recent animal and retrospective human data suggest that the general anesthetics commonly used in pediatric medicine could be damaging to the developing brain when used at clinical concentrations.In vivo primate and rodent models have shown that neonatal exposure to clinical concentrations of anesthetics causes neural apoptosis
