Stroke-Like Migraine Attacks After Radiation Therapy (SMART) Syndrome: A Case Report.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare and delayed complication of brain irradiation involving impaired cerebrovascular autoregulation, and diagnosis is based on distinct clinic-radiographic findings and exclusion of differentials. We report a 38-year-old man, who received cranial irradiation 28 years before and developed episodes of headache and visual aura, followed by left hemianopia, aphasia, behavioral disturbances, and focal seizures. An MRI of the brain revealed gyral swelling with restricted diffusion and mild contrast enhancement over the right temporoparietal and occipital region, and fludeoxyglucose-FDG PET scan showed hyperperfusion in the corresponding brain region. He improved completely with pulse steroids and antiseizure medications. The recognition of this syndrome is important as we can reassure patients and their families and help avoid unnecessary and invasive diagnostic tests.

Safety outcomes of teclistamab accelerated dose escalation.

INTRODUCTION: Teclistamab, a bispecific T-cell engaging antibody targeting B-cell maturation antigen (BCMA), is indicated for the treatment of relapsed or refractory multiple myeloma after at least four lines of therapy. It has boxed warnings for life threatening cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). To mitigate these risks, teclistamab is initiated using step-up doses. This article examines safety event rates following the implementation of a 2-day separation between step-up doses at one institution to streamline patient care. METHODS: This was a retrospective, single-center study encompassing all patients who received teclistamab within a 1-year period. The primary endpoint was the overall incidence of CRS and ICANS. Secondary endpoints included hospital length of stay, hematological toxicities, infection rates, among other adverse events. RESULTS: A total of 27 patients were included in the analysis and stratified into accelerated (days 1,3,5) or standard (days 1,4,7) dosing groups. CRS occurred in 48% (11) of patients for the accelerated dosing and 50% (2) for the standard dosing group. ICANS was seen in 17% (4) of patients in the accelerated dosing group and none in the standard dosing group. Average length of stay in the accelerated dose was 7.6 days versus 9.2 days in the standard dose group. CONCLUSION: Accelerated dose escalation of teclistamab yielded safety event rates comparable to those in the literature. These findings may support outpatient administration for teclistamab. Accelerated dose escalation strategy allowed for the optimization of hospitalization and resources.

African mesquite elicits neuroprotective activity against quaternary metal mixture -induced olfactory bulb-hippocampal oxido-inflammatory stress via nrf2-hmox-1pathway.

African mesquite AM is widely used as an anti-inflammatory agent in sub-Sahara Africa especially Nigeria. Given its strong anti-inflammatory potency, this study has evaluated the neuroprotective properties of AM in the hippocampus HIP and olfactory bulb OB of rats exposed to Cd, As, Hg, and Pb. Twenty-five albino Sprague Dawley rats were randomly divided into five groups in this experiment. Group 1, the control received only water. Group 2 received heavy metal mixture HMM (PbCl2 (20 mg/kg), CdCl2 (1.61 mg/kg), HgCl2 (0.40 mg/kg), and NaAsO3 (10 mg/kg), for 60 days. Groups 3, 4, and 5 were treated with HMM along with AM at doses of 500, 1000, and 1500 mg/kg, respectively. AM decreased the Cd, As, Hg, and Pb levels in OB and HIP, restored the activities of antioxidants, Hmox-1, reduced the activities of AChE, NRF2 and NFkB and improved histopathology.

Unveiling the hidden dangers: a review of non-apoptotic programmed cell death in anesthetic-induced developmental neurotoxicity.

Anesthetic-induced developmental neurotoxicity (AIDN) can arise due to various factors, among which aberrant nerve cell death is a prominent risk factor. Animal studies have reported that repeated or prolonged anesthetic exposure can cause significant neuroapoptosis in the developing brain. Lately, non-apoptotic programmed cell deaths (PCDs), characterized by inflammation and oxidative stress, have gained increasing attention. Substantial evidence suggests that non-apoptotic PCDs are essential for neuronal cell death in AIDN compared to apoptosis. This article examines relevant publications in the PubMed database until April 2024. Only original articles in English that investigated the potential manifestations of non-apoptotic PCD in AIDN were analysed. Specifically, it investigates necroptosis, pyroptosis, ferroptosis, and parthanatos, elucidating the signaling mechanisms associated with each form. Furthermore, this study explores the potential relevance of these non-apoptotic PCDs pathways to the pathological mechanisms underlying AIDN, drawing upon their distinctive characteristics. Despite the considerable challenges involved in translating fundamental scientific knowledge into clinical therapeutic interventions, this comprehensive review offers a theoretical foundation for developing innovative preventive and treatment strategies targeting non-apoptotic PCDs in the context of AIDN.

Vitamin B6 Via p-JNK/Nrf-2/NF-κB Signaling Ameliorates Cadmium Chloride-Induced Oxidative Stress Mediated Memory Deficits in Mice Hippocampus.

BACKGROUND: Cadmium chloride (Cd) is a pervasive environmental heavy metal pollutant linked to mitochondrial dysfunction, memory loss, and genetic disorders, particularly in the context of neurodegenerative diseases like Alzheimer's disease (AD). METHODS: This study investigated the neurotherapeutic potential of vitamin B6 (Vit. B6) in mitigating Cd-induced oxidative stress and neuroinflammation-mediated synaptic and memory dysfunction. Adult albino mice were divided into four groups: Control (saline-treated), Cd-treated, Cd+Vit. B6- treated, and Vit. B6 alone-treated. Cd and Vit. B6 were administered intraperitoneally, and behavioral tests (Morris Water Maze, Y-Maze) were conducted. Subsequently, western blotting, antioxidant assays, blood glucose, and hyperlipidemia assessments were performed. RESULTS: Cd-treated mice exhibited impaired cognitive function, while Cd+Vit. B6-treated mice showed significant improvement. Cd-induced neurotoxic effects, including oxidative stress and neuroinflammation, were observed, along with disruptions in synaptic proteins (SYP and PSD95) and activation of p-JNK. Vit. B6 administration mitigated these effects, restoring synaptic and memory deficits. Molecular docking and MD simulation studies confirmed Vit. B6's inhibitory effect on IL-1ß, NRF2, and p-JNK proteins. CONCLUSION: These results highlight Vit. B6 as a safe therapeutic supplement to mitigate neurodegenerative disorders, emphasizing the importance of assessing nutritional interventions for combating environmental neurotoxicity in the interest of public health.

Baclofen-induced neurotoxicity in a dialysis patient managed with continuous venovenous hemodialysis: A case report and literature review.

Despite documented cases of baclofen toxicity in individuals with kidney disease, the drug is widely prescribed for various medical conditions, primarily spasticity, hiccups, and multiple sclerosis. Baclofen, a gamma-aminobutyric acid derivative, relies on renal excretion, rendering those with impaired kidney function susceptible to toxicity - a concern often underestimated by health-care providers. Adverse reactions, including single or double doses, are well documented in addition to multi-dose toxicity. This report discusses a case of baclofen-induced neurotoxicity in an end-stage renal disease patient undergoing dialysis, highlighting the subsequent management with continuous venovenous hemodialysis. In addition, it provides a comprehensive review of existing literature on baclofen toxicity in cases of renal insufficiency. Strikingly, the literature lacks clear guidelines regarding baclofen safety, dose adjustments, or renal function thresholds for contraindication. This contribution aims to augment understanding of this critical issue, emphasizing the need for heightened awareness and careful consideration of baclofen use in patients with kidney disease.

A developmental neurotoxicity adverse outcome pathway (DNT-AOP) with voltage gate sodium channel (VGSC) inhibition as a molecular initiating event (MiE).

The adverse outcome pathway (AOP) framework serves as a practical tool for organising scientific knowledge that can be used to infer cause-effect relationships between stressor events and toxicity outcomes in intact organisms. However, a major challenge in the broader application of the AOP concept within regulatory toxicology is the development of a robust AOPs that can withstand peer review and acceptance. This is mainly due to the considerable amount of work required to substantiate the modular units of a complete AOP, which can take years from inception to completion. The methodology used here consisted of an initial assessment of a single chemical hazard using the Integrated Approach to Testing and Assessment (IATA) framework. An evidence-based approach was then used to gather empirical evidence combining systematic literature review methods with expert knowledge to ensure the effectiveness of the AOP development methodology. The structured framework used assured transparency, objectivity and comprehensiveness, and included expert knowledge elicitation for the evaluation of key event relationships (KERs). This stepwise approach led to the development of an AOP that begins with binding of chemicals to Voltage Gate Sodium Channels (VGSC/Nav) during mammalian development leading to adverse consequences in neurodevelopment evidenced as deficits in cognitive functions. Disruption of the formation of precise neural circuits by alterations in VGSC kinetics during the perinatal stages of brain development may also underlie neurodevelopmental disorders. Gaps in our understanding include the specific critical developmental windows and the quantitative relationship of binding to VGSC and subsequent disruption and cognitive function. Despite the limited quantitative information at all KER levels, regulatory applications of this AOP for DNT assessment have been identified.

Predictors of prolonged supratherapeutic serum lithium concentrations: a retrospective chart review.

INTRODUCTION: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup suggests hemodialysis in severe lithium poisoning if specific criteria are met. One criterion is if the expected time to obtain a lithium concentration <1.0 mEq/L with optimal management is >36 h. There are a lack of data regarding which patient characteristics are associated with the rate at which patients achieve a lithium concentration <1.0 mEq/L. METHODS: We conducted a retrospective chart review analyzing hospital electronic medical records. Inclusion criteria consisted of a lithium concentration >1.2 mEq/L during hospitalization. We excluded patients who received extracorporeal treatment before 36 h elapsed from time of initial lithium concentration >1.2 mEq/L. The primary analysis consisted of a Cox regression and a secondary analysis evaluated the nomogram method described by Buckley and colleagues for predicting prolonged supratherapeutic lithium concentration. RESULTS: One hundred and one patients were included in the study. The median time to reach a lithium concentration <1.0 mEq/L was 42.5 h (IQR: 33.8-51.1). Older patients, patients taking a thiazide, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, patients with a higher initial lithium concentration, and patients with higher sodium concentrations achieved a lithium concentration <1 mEq/L at a slower rate. For the nomogram analysis, sensitivity (61.5%) and specificity (54.5%) were moderate, the positive predictive value (16.7%) was poor, and the negative predictive value (90.6%) was excellent. DISCUSSION: The results from our primary analysis suggest that identifying higher serum sodium concentration and use of certain antihypertensives that decrease glomerular filtration rate as predictors of an increased time to reach a therapeutic lithium concentration may help identify patients who meet the Extracorporeal Treatments in Poisoning criteria for hemodialysis. The nomogram method performed similarly to prior validation studies. CONCLUSIONS: In this retrospective chart review of patients with supratherapeutic lithium concentrations, we identified several risk factors for prolonged supratherapeutic lithium concentrations.

Rosiglitazone Promotes Oligodendrocyte Development and Myelin Formation of Repeated Neonatal Sevoflurane Exposure via PPARγ Signaling.

Sevoflurane is one of the most commonly used general anesthetics for children and infants. Recent research indicates that repeated exposure to sevoflurane in neonates induces cognitive and fine motor deficits. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have garnered significant attention as potential therapies for a variety of neurological conditions. In this research, we evaluated whether pretreatment with rosiglitazone in neonatal mice could address myelination defects, cognitive impairment, and fine motor dysfunction via PPARγ. The mice were exposed to 3% sevoflurane for 2 h on postnatal days 6-8 (P6-P8). Behavioral tests were conducted from P29 to P34. Additionally, we evaluated morphological and functional changes related to myelin. Our results showed that rosiglitazone pretreatment significantly ameliorated the cognitive and fine motor impairments of repeated neonatal sevoflurane exposure. In addition, rosiglitazone pretreatment promoted oligodendrocyte precursor cells (OPCs) differentiation and myelination. This suggests that rosiglitazone may be used in clinical settings to enhance the security of neonatal sevoflurane exposure. Furthermore, PPARγ and fatty acid synthase (FASN) may be mediators for rosiglitazone, which alleviates myelination defects, cognitive impairment, and fine motor dysfunction.

Quercetin alleviates 6-OHDA-caused apoptosis in SH-SY5Y cells.

Aim: This study is primarily designed to investigate the potential neuroprotective effects of polyphenol against 6-OHDAcaused neurotoxicity on SH-SY5Y cells. Materials and Methods: Cytotoxic effect of 6-OHDA and valuable role of quercetin, myricetin and kaempferol on SH-SY5Y cells were analyzed by MTT assay. Generation of 6-OHDA-stimulated reactive oxygen species (ROS) was measured using DCFDA fluorescence dye. Alteration of 6-OHDA-caused mitochondrial membrane potential and nuclear condensation was investigated with the help of rhodamine-123 and hoechest stain. Immunoblotting was performed to detect the expression level of 6-OHDA-caused alpha-synuclein (á-syn), Bcl-2 associated protein X (BAX), caspase 3, cleaved Poly ADP - ribose polymerase (PARP) and Bcell lymphoma 2 proteins (Bcl-2). Result: Through MTT assay, quercetin was selected over myricetin and kaempferol to counter 6-OHDA-caused cell death. The research delves into unraveling the intricate mechanisms underlying 6-OHDA-induced neurotoxicity, encompassing alterations in cellular morphology, escalation of oxidative stress, perturbation in mitochondrial membrane potential, and nuclear condensation. Exposure to 6-OHDA is implicated in the upregulation of á-syn protein, contributing to the aggravation of neurotoxicity. Concurrently, 6-OHDA orchestrates the apoptotic pathway by upregulating the expression of proapoptotic proteins such as BAX, caspase 3, and PARP, while down regulating the expression of the Bcl-2, affirming its role in apoptosis induction. Quercetin demonstrated ability to attenuate the expression of á-syn in the presence of 6-OHDA-caused injury in SH-SY5Y cells. Conclusion: Taken together, these findings collectively underscore the therapeutic potential of quercetin as a promising agent against neurotoxicity caused by 6-OHDA.

Chimeric Antigen Receptor (CAR) T-Cell Therapy Use in Patients with Multiple Myeloma and Kidney Failure on Maintenance Hemodialysis: A Report of 2 Cases.

Chimeric antigen receptor (CAR) T-cell therapy against B-cell maturation antigen is a new treatment modality for relapsed or refractory multiple myeloma (MM). Patients with kidney failure and MM were excluded from the pivotal CAR T-cell therapy clinical trials: KaRMMa (idecabtagene vicleucel) and CARTITUDE (ciltacabtagene autocleucel). The safety and efficacy of CAR T-cell therapy in patients with relapsed or refractory MM and kidney failure are limited to a few case reports using idecabtagene vicleucel. Here, we report the first 2 cases of ciltacabtagene autoleucel use in patients with kidney failure on maintenance hemodialysis and relapsed or refractory MM. Both patients achieved a hematologic response following ciltacabtagene autoleucel administration without serious adverse events. These findings suggest that ciltacabtagene autoleucel may be safe and effective in patients with relapsed or refractory MM and kidney failure. In this report, we review the available literature regarding the use of CAR T-cell therapy in patients with MM and kidney failure. We also discuss the modification of the lymphodepletion regimen in the kidney failure setting.

Neurotoxic Methamphetamine Doses Alter CDCel-1 Levels and Its Interaction with Vesicular Monoamine Transporter-2 in Rat Striatum.

In recent years, methamphetamine METH misuse in the US has been rapidly increasing and there is no FDA-approved pharmacotherapy for METH use disorder (MUD). In addition to being dependent on the drug, people with MUD develop a variety of neurological problems related to the toxicity of this drug. A variety of molecular mechanisms underlying METH neurotoxicity has been identified, including dysfunction of the neuroprotective protein parkin. However, it is not known whether parkin loss of function within striatal dopaminergic (DAergic) terminals translates into a decrease in DA storage capacity. This study examined the relationship between parkin, its substrate cell division cycle related-1 (CDCrel-1), and vesicular monoamine transporter-2 (VMAT2) in METH neurotoxicity in male Sprague Dawley rats. To also assess individual differences in response to METH's neurotoxic effects, a large group of rats was treated with binge METH or saline and sacrificed 1h or 24h later. This study is the first to show that binge METH alters the levels and subcellular localization of CDCrel-1 and that CDCrel-1 interacts with VMAT2 and increases its levels at the plasma membrane. Furthermore, we found wide individual differences in the responses of measured indices to METH. Proteomic analysis of VMAT-2-associated proteins revealed upregulation of several proteins involved in the exocytosis/endocytosis cycle. The results suggest that at 1h after METH binge, DAergic neurons are engaged in counteracting METH-induced toxic effects, including oxidative stress- and hyperthermia-induced inhibition of synaptic vesicle cycling, with the responses varying between individual rats. Studying CDCrel-1, VMAT2, and other proteins in large groups of outbred rats can help define individual genetic and molecular differences in responses to METH neurotoxicity which, in turn, will aid treating humans suffering from METH use disorder and its neurological consequences.

Behavioral neuroscience in zebrafish: unravelling the complexity of brain-behavior relationships.

This paper reviews the utility of zebrafish (Danio rerio) as a model system for exploring neurobehavioral phenomena in preclinical research, focusing on physiological processes, disorders, and neurotoxicity biomarkers. A comprehensive review of the current literature was conducted to summarize the various behavioral characteristics of zebrafish. The study examined the etiological agents used to induce neurotoxicity and the biomarkers involved, including Aß42, tau, MMP-13, MAO, NF-Кß, and GFAP. Additionally, the different zebrafish study models and their responses to neurobehavioral analysis were discussed. The review identified several key biomarkers of neurotoxicity in zebrafish, each impacting different aspects of neurogenesis, inflammation, and neurodegeneration. Aß42 was found to alter neuronal growth and stem cell function. Tau's interaction with tubulin affected microtubule stability and led to tauopathies under pathological conditions. MMP-13 was linked to oxidative assault and sensory neuron degeneration. MAO plays a role in neurotransmitter metabolism and neurotoxicity conversion. NF-Ðšß was involved in pro-inflammatory pathways, and GFAP was indicative of neuroinflammation and astroglial activation. Zebrafish provide a valuable model for neurobehavioral research, adhering to the "3Rs" philosophy. Their neurotoxicity biomarkers offer insights into the mechanisms of neurogenesis, inflammation, and neurodegeneration. This model system aids in evaluating physiological and pathological conditions, enhancing our understanding of neurobehavioral phenomena and potential therapeutic interventions.

In vivo and in vitro effects of crocetin and its amide derivative on acrylamide-induced neurotoxicity.

Objective: Acrylamide (ACR) is a neurotoxic agent whose damage could be attenuated by antioxidants administration. Crocetin is a saffron-derived antioxidant that has neuroprotective effects. This study evaluates the protective effects of trans-sodium crocetinate (TSC) and its water-soluble derivative, Bis-N-(N-methylpyprazinyl) crocetinate (BMPC) against ACR neurotoxicity. Materials and Methods: PC12 cells were treated with TSC and BMPC (1.95, 3.9, 7.81, 15.62, 31.25, 62.5, 125, 250, 500, and 1000 µM) for 24 hr. ACR was then added at a concentration of 6.5 mM (IC50), and cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide. In the in vivo study, male Wistar rats were treated with ACR (50 mg/kg, intraperitoneal (i.p.)) for 11 days alone or in combination with TSC and BMPC (2.5, 5, and 10 mg/kg, i.p.) or vitamin E (200 IU/kg, i.p.). Motor impairments were then evaluated. The cerebral cortex of sacrificed rats was taken for the malondialdehyde (MDA) and glutathione (GSH) levels measurement. Results: In vitro studies showed that TSC at a concentration of 7.81 µM and BMPC at concentrations of 3.9, 7.81, and 15.62 µM exhibited the lowest toxicity in acrylamide administration. In the in vivo study, pretreatment with 2.5, 5, and 10 mg/kg of TSC ameliorated behavioral impairments, but BMPC could not attenuate them. GSH and MDA were improved by 2.5, 5, and 10 mg/kg TSC and 2.5 mg/kg BMPC. Conclusion: TSC and BMPC administration improved behavioral index and oxidative stress injuries in Wistar rats exposed to ACR through MDA reduction and GSH content enhancement in the cerebral cortex.

Investigation of the effects of curcumin and piperine on cyclophosphamide-induced brain injury in rats.

Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy. Curcumin (CUR) and piperine (PP) show a protective effect on neurodegenerative and neurological diseases. This research was designed to measure several biochemical parameters in the brain tissue of CP-applied rats to investigate the impact of combined CUR-PP administration. The study evaluated six groups of eight rats: Group 1 was the control; Groups 2 and 3 were administered 200 or 300 mg/kg CUR-PP via oral gavage; Group 4 received only 200 mg/kg CP on day 1; Groups 5 and 6 received CP + CUR-PP for 7 days. Data from all parameters indicated that CP caused brain damage. Phosphorylated TAU (pTAU), amyloid-beta peptide 1-42 (Aß1-42), glutamate (GLU), and gamma amino butyric acid (GABA) parameters were the same in Groups 4, 5, and 6. On the other hand, 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), interleukin-6 (IL-6), nuclear factor kappa beta (NF-kß), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels in the CP + CUR-PP groups were lower than those in the CP group (p < 0.05). However, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) parameters were higher in the CP + CUR-PP groups compared to the CP group (p < 0.05). It is thought that the similarity of Groups 5 and 6 with Group 4 in Aß1-42, pTAU, GLU, and GABA parameters hinder the determination of treatment protection however, they might have a therapeutic effect if the applied dose or study duration were changed. This study attempted to evaluate the effects of a CUR-PP combination on CP-induced brain damage in rats by measuring biochemical parameters and performing histopathological examinations. Based on the findings, this CUR-PP combination could be considered an alternative medicine option in cases with conditions similar to those evaluated in this study.

Neurobehavioral, neurotransmitter and redox modifications in Nauphoeta cinerea under mixed heavy metal (silver and mercury) exposure.

Heavy metals are encountered in nature, and are used in several human endeavors, including in dental fillings. It is well known that the safety of metals depends on their chemical form, as well as the dose and route through which biological systems are exposed to them. Here, we used the Nauphoeta cinerea model to examine the mechanism by which salts of the heavy metals used in dental fillings - silver and mercury - exert their neurotoxicity. Nymphs exposed to heavy metals presented with reduced motor and exploratory abilities as they spent more time immobile, especially in the periphery of a novel object, and covered less distance compared with control nymphs. Exposure to AgNO3 and HgCl2 also exacerbated levels of oxidative stress markers (MDA & ROS) and the neurotransmitter regulators - AChE and MAO, while reducing antioxidant activity markers, both in biochemical (thiol & GST) and RT-qPCR (TRX, GST, SOD, Catalase) examinations, in neural tissues of the cockroach. The observed disruptions in neurolocomotor control, synaptic transmission and redox balance explain how heavy metal salts may predispose organisms to neurological disorders.

Behavioral, biochemical, histopathological evaluation and gene expression of brain injury induced by nanoceria injected intranasal or intraperitoneal in mice.

Background: Nanotechnology has shown a remarkable progress nevertheless, there is a growing concern about probable neurotoxic and neurodegenerative effects due to NPs exposure. Various toxicological and epidemiological studies reported that the brain is a main target for ultrafine particles. Brain inflammation is considered as a possible mechanism that can participate to neurotoxic and neurodegenerative effects. Whether nanoparticles (NPs) may produce neurotoxicity and promote neurodegenerative is largely unstudied. The present study was done to investigate whether intranasal and intra-peritoneal exposure to cerium oxide nanoparticles (CeO2NPs, nanoceria (NC)) could cause neurotoxicity and neurodegenerative changes in the brain tissue through conducting some behavioral tests, biochemical evaluation, histopathological examinations of brain hippocampus and gene expressions. Method: Fifteen mice were separated into 3 equal groups. In group (I) "control group", mice were received distilled water orally and kept as a control group. Mice in the group (II) "NC I/P group" were injected i.p with cerium oxide nanoparticles at a dose of 40 mg/kg b.wt, twice weekly for 3 weeks. In group (III) "NC I/N group" mice were received nanoceria intranasally (40 mg/kg b.wt), twice weekly for 3 weeks. Results: Exposure to nanceria resulted in oxidative damage in brain tissue, a significant increase in malondialdehyde (MDA) and acetylcholinestrase (AchE) levels, significant decrease in reduced glutathione (GSH) concentration, upregulation in the apoptosis-related genes (c-Jun: c-Jun N-terminal kinases (JNKs), c-Fos: Fos protooncogene, AP-1 transcription factor subunit, c-Myc: c-myelocytomatosis oncogene product or MYC protooncogene, bHLH transcription factor), locomotor and cognitive impairment in mice but the effect was more obvious when nanoceria adminstred intraperitoneally. Conculsion: Nanoceria cause oxidative damage in brain tissue of mice when adminstred nanoceria intraperitoneally more than those received nanoceria intranasal.

The pollutant perfluorohexane sulfonate (PFHxS) reduces serum thyroxine but does not alter thyroid action in the postnatal rat brain.

Known as "forever chemicals", per- and polyfluoroalkyl substances (PFAS) are synthetic compounds used in consumer goods but pose significant public health concerns, including disruption of the thyroid system. As thyroid hormones (THs) are required for normal brain development, PFAS may also be developmental neurotoxicants. However, this is not well understood. Here we examine the endocrine and neurodevelopmental consequences of perfluorohexane sulfonate (PFHxS) exposure in pregnant, lactating, and developing rats, and compare its effects to an anti-thyroid pharmaceutical (propylthiouracil, PTU) that induces thyroid-mediated developmental neurotoxicity. We show that PFHxS dramatically reduces maternal serum thyroxine (T4), nearly equivalently to PTU (-55 and -51%, respectively). However, only PTU increases thyroid stimulating hormone. The lactational transfer of PFHxS is significant and reduces pup serum T4 across the postnatal period. Surprisingly, brain THs are only minimally decreased by PFHxS, whereas PTU drastically diminishes them. Evaluation of brain TH action by phenotyping, RNA-Sequencing, and quantification of radial glia cell morphology supports that PTU interrupts TH signaling while PFHxS has limited to no effect. These data show that PFHxS induces abnormal serum TH profiles; however, there were no indications of hypothyroidism in the postnatal brain. We suggest the stark differences between the neurodevelopmental effects of PFHxS and a typical antithyroid agent may be due to its interaction with TH distributing proteins like transthyretin.

Chronic immune-related adverse events arising from immune checkpoint inhibitors: an update.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, improving outcomes for many patients. However, toxicities termed immune-related adverse events (irAEs) are limitations of these revolutionary treatments. These irAEs may resolve with treatment or ICI cessation (acute) or persist many months beyond therapy cessation (chronic). Acute irAEs were the first to be recognized and are thus more well studied. However, chronic irAEs have been highlighted in recent years and are becoming a topic of more intensive investigation. These chronic irAEs have been noted to affect many different organ systems, including endocrine, rheumatologic, gastrointestinal, dermatologic, neurologic, and cardiovascular systems. In this review, we discuss current knowledge surrounding the frequency, time course, and risk factors associated with chronic irAEs affecting various organ systems, treatment approaches, and future directions.

Parental exposure to acrylamide disrupts sphingolipid metabolism and impairs transgenerational neurodevelopment in zebrafish (Danio rerio) offspring.

Acrylamide exposure has become an emerging environmental and food safety issue, and its toxicity poses a potential threat to public health worldwide. However, limited studies have paid attention to the detrimental effects of parental exposure to acrylamide on the neurodevelopment in zebrafish offspring. In this study, the embryos were life-cycle exposed to acrylamide (0.125 and 0.25 mM) for 180 days. Subsequently, these zebrafish (F0) were allowed to mate, and their offspring (F1) were collected to culture in clean water from embryos to adults. We employed developmental and morphological observations, behavioral profiles, metabolomics analyses, and transcriptional level examinations to investigate the transgenerational neurotoxicity with parental exposure to acrylamide. Our results showed that parental exposure to acrylamide harms the birth, development, and behavior characterization of the F1 zebrafish larvae, including poor egg quality, increased mortality rates, abnormal heart rates, slowed swimming activity, and heightened anxiety behavior, and continuously disturbs mental health in F1 adult zebrafish. The transcriptional analysis showed that parental chronic exposure to acrylamide deteriorates the neurodevelopment in F1 larvae. In addition, metabolomics analyses revealed that sphingolipid metabolism disruption may be associated with the observed abnormal development and behavioral response in unexposed F1 offspring. Overall, the present study provides pioneer evidence that acrylamide induces transgenerational neurotoxicity via targeting and disrupting sphingolipid metabolism, which reveals intergenerational transmission of acrylamide exposure and unravels its spatiotemporal toxicological effect on neurodevelopment.