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Dementia encompasses a spectrum of neurodegenerative disorders significantly impacting global health, with environmental factors increasingly recognized as crucial in their etiology. Among these, ozone, has been identified as a potential exacerbator of neurodegenerative processes, particularly in Alzheimer's disease (AD). Ozone exposure induces the production of reactive oxygen species (ROS), which penetrate the BBB, leading to oxidative damage in neuronal cells. This oxidative stress is closely linked with mitochondrial dysfunction and lipid peroxidation, processes that are foundational to the pathology observed in dementia, such as neuronal death and protein aggregation. Furthermore, ozone triggers chronic neuroinflammation, exacerbating these neurodegenerative processes and perpetuating a cycle of CNS damage. Recent studies highlight the role of peripheral biomarkers like High Mobility Group Box 1 (HMGB1) and Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in mediating ozone's effects. Disruption of these and other identified proteins by ozone exposure impairs microglial function and response to amyloid plaques, suggesting a novel pathway through which ozone may influence AD pathology via immune dysregulation. This review discusses the concept of a bidirectional lung-brain axis, illustrating that systemic responses to air pollutants like ozone may reflect and contribute to neurodegenerative processes in the CNS. By delineating these mechanisms, we emphasize the critical need for integrating environmental health management into strategies for the prevention and treatment of dementia. [ABSTRACT FROM AUTHOR]

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here, we report that bilirubin (BIL)-dependent cell death in the auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated current (Ih), or by genetic deletion of HCN1. GABAergic inhibitory interneurons predominantly express HCN1, on which BIL selectively acts to increase their intrinsic excitability and mortality by enhancing HCN1 activity and Ca2+-dependent membrane targeting. Chronic BIL elevation in neonatal mice in vivo increases the fraction of spontaneously active interneurons and their firing frequency, Ih, and death, compromising audition at the young adult stage in HCN1+/+, but not in HCN1-/- genotype. We conclude that HB preferentially targets HCN1 to injure inhibitory interneurons, fueling a feedforward loop in which lessening inhibition cascades hyperexcitability, Ca2+ overload, neuronal death, and auditory impairments. These findings rationalize HCN1 as a potential target for managing HB encephalopathy. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton beam radiation therapy is one of the major treatment modalities used for cancer treatment, including brain tumors. This treatment modality is distinct from other radiation options because of its ability to deliver radiation to tumor targets while sparing healthy tissue. Brainstem toxicity is a rare but important complication can arise due to exposure to radiation; hence, in this systematic review and meta-analysis, we aimed to explore the risk of brainstem toxicity in pediatric brain tumor patients undergoing proton beam radiation, focusing on quantifying its incidence and severity. Eleven articles were considered eligible in our study, and the results yielded an overall brainstem toxicity incidence of 1.8%, ranging in severity, with Grade 1 brainstem toxicity (asymptomatic) being the most common. This study revealed a low incidence of symptomatic brainstem toxicity and related mortality among pediatric brain tumor patients undergoing proton beam radiation, which could support the idea of it having a good toxicity profile and possibly re-enforces the need for more comprehensive primary studies regarding this radiation modality in brain tumor patients to uncover unknowns and help us understand the grey areas of this topic. Background: Proton beam radiation therapy (PBRT) is an advanced cancer treatment modality that utilizes the distinctive physical properties of protons to precisely deliver radiation to tumor targets while sparing healthy tissue. This cannot be obtained with photon radiation. In this systematic review and meta-analysis, we aimed to comprehensively assess the risk of brainstem toxicity in pediatric brain tumor patients undergoing PBRT. Methods: With adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a predetermined search strategy was used to identify eligible articles from PubMed, Web of Science, Scopus, and Cochrane Library through July 2024. Results: The current study included a total of 11 eligible articles. The pooled prevalence of patients who suffered from brainstem toxicity was 1.8% (95% CI: 1%, 2.6%). The pooled prevalences of patients with Grade 1 to Grade 5 brainstem toxicity were found to be 10.6% (95% CI: 8.8%, 30%), 1.5% (95% CI: 0.6%, 2.5%), 0.7% (95% CI: 0.3%, 1.1%), 0.4% (95% CI: 0.1%, 0.7%), and 0.4% (95% CI: 0.1%, 0.8%), respectively, with an overall pooled prevalence of 0.7% (95% CI: 0.4%, 1%). Conclusions: This study revealed a relatively low incidence of symptomatic brainstem toxicity and its related mortality in the pediatric population undergoing PBRT. However, further research is encouraged to study the broader effects of PBRT and to explore various factors that may influence the risk of brainstem toxicity in patients treated with PBRT. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer immunotherapies, while revolutionary in boosting the immune system to fight cancer, can also trigger serious side effects, including inflammation of the brain. We review the existing literature on encephalitis with a special focus on cancer treatment-related encephalitis, including its etiopathogenesis, differential diagnosis, and identification of optimal diagnostic approaches and treatment strategies. This review aims to help clinicians from oncology and neurology improve the diagnosis and management of this condition, help reduce complications, improve patient outcomes, and inform future therapeutic approaches. Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients' quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy—particularly immune checkpoint inhibitors—has become a cornerstone of cancer treatment, with up to half of metastatic cancer patients in economically developed countries now receiving these therapies. The widespread adoption of immunotherapy has led to improved survival rates and long-term remissions, even in patients with advanced metastatic disease. However, as immune modulators, these therapies can trigger a range of immune-related adverse events, including a variety of novel neurological toxicities. Among these, encephalitis is of particular concern due to its potential severity, which can compromise treatment outcomes. This review aims to provide a comprehensive overview of the literature on this condition, highlighting optimal diagnostic strategies and management approaches to mitigate the risk of significant morbidity, while also comparing encephalitis induced by immunotherapy with that caused by traditional chemotherapies and targeted oncologic treatments. [ABSTRACT FROM AUTHOR]

Clinical relevance: Pupil size evaluation using clinical examination may be important for detecting and monitoring individuals at risk of neurotoxic effects from chemical exposure, as it may enable early intervention and the implementation of preventive measures. Background: This work aimed to investigate the association between pesticide exposure and pupil size. Pupil size is regulated by muscarinic and nicotinic receptors, and it is well-established that common pesticide chemicals disrupt this regulation. Methods: Twenty agricultural workers exposed to pesticides, and twenty participants not exposed, underwent visual screening, and pupil size evaluation under mesopic and photopic conditions. Additionally, signs of neurotoxicity and pesticide exposure in both groups were evaluated using the modified version of the neurotoxic symptoms questionnaire (Q16) and measuring cholinesterase (AChE) levels in blood, respectively. Results: Agricultural workers exposed to pesticides had a score indicating medium–high level of neurotoxicity (49.85 (SD ± 8.94)) which was significantly higher (t (36) = 7.659, p ≤ 0.0001) than non-exposed participants who had low levels of neurotoxicity (27.25 SD ± 8.86). There was a significant difference in pupil size (mm) under mesopic (t (19) 4.42 p = 0.003) and scotopic (t (19) 4.63, p = 0.0002) conditions between the two groups. Additionally, there was a significant difference in AChE blood levels (t (19) 2.94 p = 0.008) between exposed and non-exposed participants, indicating that exposed workers had low levels of this enzyme (average exposed group 3381 U/L (SD ± 1306)) compared to the non-exposed group (average non-exposed group 4765 U/L (SD ± 1300)). A significant negative correlation between AChE levels, years of exposure, and pupil size was found. The latter finding importantly showed that smaller pupils are associated with the accumulation of acetylcholine or a decrease in the activity of the enzyme AChE. Conclusion: Pupil size of agricultural workers exposed to pesticides can be abnormal and is associated with neurotoxicity as indicated by symptomatology and cholinesterase levels. Evaluation of pupil size may be useful for clinically detecting neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: Isolated limb perfusion (ILP) is a regional cancer treatment in which high-dose chemotherapy is administered in an isolated extremity. The main side effect is regional toxicity, which occasionally leads to nerve damage. Measuring neuroaxonal biomarkers, might be a method predicting such complications. Therefore, the primary aim of the study is to investigate if neuronal biomarkers are measurable and alters in an isolated extremity during ILP. Secondly, if postoperative regional toxicity, alterations in sensitivity, and/or muscle strength are correlated to the biomarker levels. Methods: Eighteen scheduled ILP-patients were included in the study. Glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and tau concentrations were measured in plasma sampled preoperatively, at the start and end of the ILP, on days 3 and 30, using ultrasensitive Single molecule array (Simoa) technology. The patients were assessed by a physiotherapist pre- and postoperatively. Results: At ILP end, significantly higher NfL and tau levels were measured in the extremity than in the corresponding systemic circulation (NfL; 17 vs 6 ng/L, p <.01, tau; 1.8 vs 0.6 ng/L, p <.01), and the extremity levels were significantly increased at ILP end (NfL; 66 ± 37%, p <.001, tau; 75 ± 45%, p =.001). On days 3 and 30, significantly increased NfL and GFAP levels were measured systemically (NfL day 3: 69 ± 30%, p <.001; day 30: 76 ± 26%, p <.001; GFAP day 3: 33 ± 22%, p <.002; day 30: 33 ± 23%, p ≤.004). Finally, no significant correlations were found between regional toxicity or between postoperative muscle or sensitivity decrease and biomarker release. Conclusion: During ILP, NfL and tau levels increased significantly. No obvious correlations were observed between biomarker release and regional toxicity or decreased muscle strength or sensitivity, although large-scale studies are warranted. [ABSTRACT FROM AUTHOR]

[Display omitted] • Activation of astrocytic NMDARs rescued Aβ-induced reduction of BDNF in astrocytes. • Activation of astrocytic NMDARs inhibited Aβ-induced elevation of astrocytic GFAP. • Activation of astrocytic NMDARs inhibited Aβ-induced elevation of astrocytic C3. • Activation of astrocytic NMDARs inhibited Aβ-induced increase of astrocytic pNF-κB. N-methyl-D-aspartate receptors (NMDARs) play a crucial role in mediating Amyloid-β (Aβ) synaptotoxicity. Our previous studies have demonstrated an opposite (neuroprotection and neurotoxicity) effect of activating astrocytic and neuronal NMDARs with higher dose (10 μM) of NMDA, an agonist of NMDARs. By contrast, activating neuronal or astrocyitc NMDARs with lower dose (1 μM) of NMDA both exerts neuroprotective effect in Aβ-induced neurotoxicity. However, the underlying mechanism of activating astrocytic NMDARs with lower dose of NMDA to protect against Aβ neurotoxicity remains unclear. Based on our previous related work, in this study, using a co-cultured cell model of primary hippocampal neurons and astrocytes, we further investigated the possible factors involved in 1 μM of NMDA activating astrocytic NMDARs to oppose Aβ-induced synaptotoxicity. Our results showed that activation of astrocytic NMDARs by 1 μM NMDA rescued Aβ-induced reduction of brain-derived neurotrophic factor (BDNF), and inhibited Aβ-induced increase of GFAP, complement 3 (C3) and activation of NF-κB. Furthermore, blockade of astrocytic GluN2A with TCN201 abrogated the ability of 1 μM NMDA to counteract the effects of Aβ decreasing BDNF, and increasing GFAP, C3 and activation of NF-κB. These findings suggest that activation of astrocytic NMDARs protect against Aβ-induced synaptotoxicity probably through elevating BDNF and suppressing GFAP and C3. Our present research provides valuable insights for elucidating the underlying mechanism of astrocytic NMDARs activation resisting the toxic effects of Aβ. [ABSTRACT FROM AUTHOR]

The increasing prevalence of neurodevelopmental disorders has highlighted the need for improved testing methods to determine developmental neurotoxicity (DNT) hazard for thousands of chemicals. This paper proposes the integration of organoid intelligence (OI); leveraging brain organoids to study neuroplasticity in vitro, into the DNT testing paradigm. OI brings a new approach to measure the impacts of xenobiotics on plasticity mechanisms - a critical biological process that is not adequately covered in current DNT in vitro assays. Finally, the integration of artificial intelligence (AI) techniques will further facilitate the analysis of complex brain organoid data to study these plasticity mechanisms. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate human neurotoxicity and genotoxicity risks from dietary and endogenous methylglyoxal (MGO), utilizing physiologically based kinetic (PBK) modeling-facilitated reverse dosimetry as a new approach methodology (NAM) to extrapolate in vitro toxicity data to in vivo dose-response predictions. A human PBK model was defined based on a newly developed and evaluated mouse model enabling the translation of in vitro toxicity data for MGO from human stem cell-derived neurons and WM-266-4 melanoma cells into quantitative human in vivo toxicity data and subsequent risk assessment by the margin of exposure (MOE) approach. The results show that the MOEs resulting from daily dietary intake did not raise a concern for endpoints for neurotoxicity including mitochondrial function, cytotoxicity, and apoptosis, while those for DNA adduct formation could not exclude a concern over genotoxicity. Endogenous MGO formation, especially under diabetic conditions, resulted in MOEs that raised concern not only for genotoxicity but also for some of the neurotoxicity endpoints evaluated. Thus, the results also point to the importance of taking the endogenous levels into account in the risk assessment of MGO. [ABSTRACT FROM AUTHOR]

This review describes an in-depth analysis of the neurotoxicity associated with the anesthetic agents used during fetal surgery, intending to highlight the importance of understanding the effects of general anesthetics on the developing brain, particularly in the context of open fetal surgery, where high doses are applied to facilitate surgical access and augment uterine relaxation. We examined evidence from preclinical studies in rodents and primates, along with studies in human subjects, with the results collectively suggesting that general anesthetics can disrupt brain development and lead to long-lasting neurological deficits. Our review underscores the clinical implications of these findings, indicating an association between extensive anesthetic exposure in early life and subsequent cognitive deficits. The current standard of anesthetic care for fetal surgical procedures was scrutinized, and recommendations have been proposed to mitigate the risk of anesthetic neurotoxicity. These recommendations emphasize the need for careful selection of anesthetic techniques to minimize fetal exposure to potentially harmful agents. In conclusion, while the benefits of fetal surgery in addressing immediate risks often outweigh the potential neurotoxic effects of anesthesia, the long-term developmental impacts nevertheless warrant consideration. Our analysis suggests that the use of general anesthetics in fetal surgery, especially at high doses, poses a significant risk of developmental neurotoxicity. As such, it is imperative to explore safer alternatives, such as employing different methods of uterine relaxation and minimizing the use of general anesthetics, to achieve the necessary surgical conditions. Further research, particularly in clinical settings, is essential to fully understand the risks and benefits of anesthetic techniques in fetal surgery. [ABSTRACT FROM AUTHOR]

Amyloid beta (Aβ) deposition in the brain is regarded as an early toxic effect in the aetiopathogenesis of Alzheimer's Disease (AD). Currently, Aβ is considered a key marker for AD and a promising target for drug development for the future management of debilitating diseases such as AD. However, the pathomechanism of Aβ has not yet been precisely understood in terms of AD patients, specifically regarding the pathological forms of Aβ and how it associates with other biochemical markers to cause dementia. Identifying Aβ as a key hallmark, especially at the earliest stages of the disease, is essential for understanding the progression of AD and its applicability for the development of novel therapeutics aimed at managing cognitive impairment and AD. This review aims to explain the neurotoxicity of Aβ and its correlation with various other biological markers that contribute to the induction of AD and memory deterioration. [ABSTRACT FROM AUTHOR]

Diabetes-induced neuropathy represents a major etiology of dementia, highlighting an urgent need for the development of effective therapeutic interventions. In this study, we explored the role of fibronectin type III domain containing 5 (FNDC5)/Irisin in mitigating hyperglycemia-induced neurotoxicity in HT22 cells and investigated the underlying mechanisms. Our findings reveal that high glucose conditions are neurotoxic, leading to reduced viability of HT22 cells and increased apoptosis. Furthermore, the elevated expression of the intracellular ferroptosis marker Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), along with increased levels of ferrous ions and malondialdehyde (MDA), suggests that high glucose conditions may induce ferroptosis in HT22 cells. FNDC5/Irisin treatment effectively mitigates high glucose-induced neurotoxicity and ferroptosis in HT22 cells. Mechanistically, FNDC5/Irisin enhances cellular antioxidant capacity, regulates ACSL4 expression, and improves intracellular redox status, thereby inhibiting ferroptosis and increasing HT22 cell survival under high-glucose conditions. These results highlight the neuroprotective potential of FNDC5/Irisin in high glucose environments, offering a promising avenue for developing treatments for diabetes-related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of some chemotherapeutic agents. Effective treatment is limited. OBJECTIVES: This single patient case details gua sha as an intervention to reduce CIPN. METHODS: A 38-year-old female patient received weekly treatment of gua sha in one-hour sessions for 10 weeks. The patient completed the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) subscale to describe her CIPN throughout and postintervention. A research assistant measured the extent of numbness or tingling along the limb from baseline to 18 months after gua sha. Descriptive data were used to summarize this case. FINDINGS: After gua sha, the total FACT/GOG-NTX subscale score increased from 13 to 36, indicating a sevenfold greater change than the minimum clinically important difference. The range of limb numbness and tingling decreased, and the symptoms remained stable during follow-up. Gua sha showed a positive clinical effect. [ABSTRACT FROM AUTHOR]

Introduction: Propylene glycol (PG) is frequently used as a solvent for various medications. However, there is substantial evidence of Propylene glycol toxicity, such as depression, agitation, and seizures, particularly when used in combination with other drugs. Here, we aimed to study the effect of Propylene glycol administration in combination with amyloid β1-40 injection on hippocampal neurons. Materials & Methods: Thirty-six male Wistar rats were randomly divided into four groups: sham, amyloid β1-40 injection group, Propylene glycol group, and amyloid β1-40+ Propylene glycol group. Alternation behavior, number of neurons in the hippocampus, lipid peroxidation markers, and superoxide dismutase levels were analyzed in all rats. Results: When Propylene glycol was co-administered with amyloid β1-40, a notable reduction in the mean neuronal count was observed in the CA1, CA3, and DG regions compared with the amyloid β1-40 only injected animals (P < 0.05). Furthermore, Propylene glycol induced an increase in lipid peroxidation markers (10.78±0.4) and a decrease in antioxidant content (2.8 ± 0.17) when administered with amyloid β1-40s compared to the animals that received only amyloid β1-40 (P<0.05). A similar pattern was found in alternation behavior compared with the group with amyloid β1-40 injection (P<0.001). Conclusion: Propylene glycol could produce excessive neurotoxicity in regions of the hippocampus when co-administered with amyloid β1-40. It likely increases lipid peroxidation and reduces superoxide dismutase in the rat brain. The use of different agents as a vehicle should be considered, especially in the elderly. [ABSTRACT FROM AUTHOR]

More than 80% of newborn infants experience jaundice as a result of elevated bilirubin during the first few weeks after birth. In most cases, hyperbilirubinemia is physiologic, but persistent and extreme elevations can lead to serious long-term complications, such as kernicterus. To avoid these complications and help clinicians in the successful assessment, evaluation, and treatment of hyperbilirubinemia, the American Academy of Pediatrics updated its clinical practice guideline for neonatal hyperbilirubinemia. This article reviews the guideline and highlights significant updates, such as an elevation in the threshold for phototherapy and exchange transfusion, inclusion of gestational age, and removal of racially based norms. [ABSTRACT FROM AUTHOR]

Neurotoxicants are substances that can lead to adverse structural or functional effects on the nervous system. These can be chemical, biological, or physical agents that can cross the blood brain barrier to damage neurons or interferewith complex interactions between the nervous system and other organs. With concerns regarding social policy, public health, andmedicine, there is a need to ensure rigorous testing for neurotoxicity. While the most common neurotoxicity tests involve using animal models, a shift towards stem cell-based platforms can potentially provide a more biologically accurate alternative in both clinical and pharmaceutical research. With this in mind, the objective of this article is to review both current technologies and recent advancements in evaluating neurotoxicants using stem cell-based approaches, with an emphasis on developmental neurotoxicants (DNTs) as these have the most potential to lead to irreversible critical damage on brain function. In the next section, attempts to develop novel predictive model approaches for the study of both neural cell fate and developmental neurotoxicity are discussed. Finally, this article concludes with a discussion of the future use of in silico methods within developmental neurotoxicity testing, and the role of regulatory bodies in promoting advancementswithin the space. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance • Unani remedies are considered safe and can be utilized as a healthcare resource due to the adverse effects of conventional pharmaceuticals. For instance, Donepezil, used to treat alzhemier’s disease exerts many adverse effects such as dizziness, vertigo, dryness of mouth. Similarly, Memantine used to slow the neurotoxicity involved in alzhemier’s disease also exerts adverse effects like vomiting, tremors and sleep disturbance. Over sixty percent of drugs are derived from synthetic basis, highlighting the potential benefits of natural Unani treatments as a safer alternative. Neurodegenerative disorders are illnesses characterized by structural and functional deterioration due to abnormal protein aggregation, resulting in inflammation and oxidative stress in the central nervous system. In unani system of medicine all current brain ailments, including alzheimer’s disease, parkinson’s disease, mania, anxiety, melancholia and others are classified under the general category of neurodegenerative disorders Their pathogenic variables and soociated symptoms and therapeutic modalities are similar. This study focuses on evidence-based Unani herbs and polyherbal formulations for the treatment of various neurodegenerative disorders. It reveals that 43 ethnomedicinal plants can be employed to treat the symptoms of neurodegenerative disorders. The material was gathered from several sources that tabulated the specific details of individual herbs and polyherbal formulations and highlighted the importance of various phytoconstituents on neuroprotective action. The research provides in vivo and scientific evidence to support the use of ethnomedicine in treating neurodegenerative disorders. Aim of the study • This study aims to validate the efficacy of Unani medicines, traditionally used for neurodegenerative diorders through evidence-based research Methods • To scan single and polyherbal formulations for neurodegenerative disorders, a literature review of traditional Unani medicine texts was conducted. To collect evidence on the efficacy of these indicated medications in the treatment of neurodegenerative disorders, electronic resources such as ScienceDirect, PubMed, Wiley Online Library, and Google Scholar were searched. The current study is a systematic review that applies inclusion and exclusion criteria rooted in the classical symptoms of neurological disorders. It evaluates the efficacy of individual herbs and polyherbal formulations recommended by Unani scholars for treatment perspectives. Results • The researchers have so far discovered 43 single drugs and 38 polyherbal formulations in Unani classical literature for treating various neurodegenerative disorders. These herbs have antioxidant, antiAlzheimer’s, anti-Parkinsonism, anti-convulsant, cognitive enhancer, anti-anxiety, neuroprotective, and anti-depressant properties, with clinical investigations proving their efficacy. The study exclusively focuses on systematic review, highlighting selected clinical studies to assess their quality and reliability of evidence. These are discussed in the introduction to provide context and understanding. Conclusions • After a thorough review of entire literature of Unani medicine, it is evident that has painstakingly focused more on physiopathology of diseases of Dimāgh wa A‘sāb including their treatment protocols .These protocols include Istifrāgh (biopurification), Taskhīn (producing warmth), Tajfiīf (desiccation), Tafrīħ-i Taba‘ (exhilaration). Research into Unani medicine has shown promising results, particularly in the use of medicinal plants known for their neuroprotective properties. One of the key advantages of Unani herbs is their natural composition, which typically consists of bioactive compounds that exert neuroprotective effects without the harsh impact often associated with synthetic drugs. For instance, herbs like Brahmi(Bacopa monnieri), Waj Turki (Acorus calamus), Chilghoza(Pinus gerardiana Wall) and Asgand (Withania somnifera) and many other plants have been studied for their ability to enhance cognitive function, reduce oxidative stress, and support neuronal health. These herbs work through various mechanisms such as antioxidant activity, anti-inflammatory properties, and modulation of neurotransmitter levels, all of which contribute to their neuroprotective potential. Nevertheless some of the compound formulations presented, that, have not yet undergone clinical testing. As a result, the researchers are advised to validate those medicines that have not yet undergone clinical evaluation. [ABSTRACT FROM AUTHOR]

• TMA+ exposure significantly inhibited the swimming activities of larval zebrafish. • Swimming path angle is the most sensitive endpoint in response to TMA+ exposure. • Neurobehavior endpoints of larvae were significantly related with oxidative stress. • The calculated 96 h-LC 50 of TMA+ was lower for zebrafish juveniles than larvae. • TMA+ evoked greater inhibitions on multi-biomarkers of juveniles than larvae. Tetramethylammonium hydroxide (TMAH) is an important compound that utilized and released by the rapidly expanding semiconductor industry, which could hardly be removed by the conventional wastewater treatment techniques. As a cholinergic agonist, the tetramethylammonium ion (TMA+) has been reported to induce toxicity to muscular and respiratory systems of mammals and human, however the toxicity on aquatic biota remains poorly known. We investigated the neurotoxic effects of TMA+ exposure on zebrafish, based on neurobehavior tests and a series of biomarkers. Significant inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L, and significant alterations on swimming path angles (straight and deflective movements) occurred even at 10 mg/L. The tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species (ROS) and malondialdehyde (MDA), significantly negatively related with the activities of antioxidant enzymes, but not significantly correlated with the level of acetylcholinesterase (AChE). Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress, rather than the alterations of neurotransmitter. At the highest exposure concentration (200 mg/L), TMA+ evoked more severe toxicity on zebrafish juveniles, showing significantly stronger elevation on the MDA activity, and greater inhibitions on the activities of antioxidant enzymes and AChE, suggesting juveniles were more susceptible to TMA+ exposure than larval zebrafish. [Display omitted] [ABSTRACT FROM AUTHOR]

The article describes cases abnormalities seen on electroencephalography (EEG) from patients experiencing neurotoxicity induced by cefepime, a cephalosporin antibiotic. A 65-year old male with a history of chronic hepatitis C and chronic right middle cerebral artery infarcts from a gliosis demonstrated right frontal sharps. A 64-year old male demonstrated myoclonic status epilepticus. An 87-year old male showed generalized sharp discharges considered as an ictal-interical continuum pattern.

The extensive utilization of the organophosphate pesticide chlorpyrifos, combined with its acute neurotoxicity, necessitates the development of effective strategies for its environmental removal. While numerous methods have been explored for chlorpyrifos removal from water, adsorption is the most promising. We investigated the potential of two cellulose-derived porous carbons as adsorbents for chlorpyrifos removal from water, prepared by either CO2 or H2O activation, resulting in similar morphologies and porosities but different amounts of heteroatom functionalities. The kinetics of batch adsorption removal from water fits well with the pseudo-first-order and pseudo-second-order kinetic models for both materials. The Freundlich, Langmuir, Dubinin–Radushkevich, and Sips isotherm models described the process of chlorpyrifos adsorption very well in all investigated cases. The maximum adsorption capacity determined from the Sips isotherm model gave values of 80.8 ± 0.1 mg g−1 and 132 ± 3 mg g−1 for the H2O and CO2 activated samples, respectively, reflecting the samples' differences in heteroatom functionalities. Additionally, the application of either adsorbent led to reduced toxicity levels in all tested samples, implying that no harmful by-products were generated during adsorption. Comparative analysis with the existing literature further validates the study's findings, suggesting the efficacy and applicability of cellulose-based porous carbons for sustainable chlorpyrifos remediation. [ABSTRACT FROM AUTHOR]

λ-cyhalothrin, a synthetic type II pyrethroid, has become increasingly popular for control of aphids, butterfly larvae, and beetles, replacing other agricultural chemicals. As a result of which, residues of this synthetic pesticide are being reported across the globe in natural water, which poses a serious threat to aquatic life. Therefore, the present study was designed to understand the toxicity effects of λ-cyhalothrin on behaviour, oxidative stress and neurotoxicity in a vertebrate aquatic model, zebrafish (Danio rerio). The fish were exposed to 0.129, 0.194 and 0.388 µg/L corresponding to 5%, 10% and 20% of 96hLC50 (1.94 µg/L) for 28 days. Upon exposure to the highest concentration (0.388 µg/L), the test animal exhibited significant alterations in behavioural patterns like number of entries to the top zone (n), decrease in average speed (m/s) and decrease in time spent in top zone (s). Moreover, the shoaling test demonstrated a significant decrease (p < 0.05) in the relative time spent by the tested fish (%) near the stimulus fish. The change in behavioural alterations might be linked to a significant decrease (p < 0.05) in the brain acetylcholine esterase activity. Furthermore, the present study also illustrates oxidative stress exerted by λ-cyhalothrin through an increase in the production of reactive oxygen species, which is again clearly depicted by a significant increase (p < 0.05) in Superoxide dismutase, Catalase and Glutathione peroxidase activities. Overall, the present study systematically demonstrates the chronic effects of λ-cyhalothrin on adult fish behaviour and physiology, which will contribute to assessing the risks of λ-cyhalothrin to organismal health. [ABSTRACT FROM AUTHOR]

Human brain development is a complex process, and animal models often have significant limitations. To address this, researchers have developed pluripotent stem cell-derived three-dimensional structures, known as brain-like organoids, to more accurately model early human brain development and disease. To enable more consistent and intuitive reproduction of early brain development, in this study, we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture. This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation, resulting in a new type of human brain organoid system. This cerebral organoid system replicated the temporospatial characteristics of early human brain development, including neuroepithelium derivation, neural progenitor cell production and maintenance, neuron differentiation and migration, and cortical layer patterning and formation, providing more consistent and reproducible organoids for developmental modeling and toxicology testing. As a proof of concept, we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins. Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns, including bursts of cortical cell death and premature differentiation. Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity, accompanied by compensatory cell proliferation at ectopic locations. The convenience, flexibility, and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental, neurological, and neurotoxicological studies.

Background: Dauricine (DAU), a benzyl tetrahydroisoquinoline alkaloid isolated from the root of Menispermum dauricum DC, exhibits promising anti-Alzheimer's disease (AD) effects, but its underlying mechanisms remain inadequately investigated. This paper aims to identify potential targets and molecular mechanisms of DAU in AD treatment. Methods: Network pharmacology and molecular docking simulation method were used to screen and focus core targets. Various transgenic Caenorhabditis elegans models were chosen to validate the anti-AD efficacy and mechanism of DAU. Results: There are 66 potential DAU-AD target intersections identified from 100 DAU and 3036 AD-related targets. Subsequent protein-protein interaction (PPI) network analysis identified 16 core targets of DAU for anti-AD. PIK3CA, AKT1 and mTOR were predicted to be the central targets with the best connectivity through the analysis of "compound-target-biological process-pathway network". Molecular docking revealed strong binding affinities between DAU and PIK3CA, AKT1, and mTOR. In vivo experiments demonstrated that DAU effectively reduced paralysis in AD nematodes caused by Aβ aggregation toxicity, downregulated expression of PIK3CA, AKT1, and mTOR homologues (age-1, akt-1, let-363), and upregulated expression of autophagy genes and the marker protein LGG-1. Simultaneously, DAU increased lysosomal content and enhanced degradation of the autophagy-related substrate protein P62. Thioflavin T（Th-T）staining experiment revealed that DAU decreased Aβ accumulation in AD nematodes. Further experiments also confirmed DAU's protein scavenging activity in polyglutamine (polyQ) aggregation nematodes. Conclusion: Collectively, the mechanism of DAU against AD may be related to the activation of the autophagy-lysosomal protein clearance pathway, which contributes to the decrease of Aβ aggregation and the restoration of protein homeostasis. [ABSTRACT FROM AUTHOR]

Human induced pluripotent stem cell-derived sensory neuron (iPSC-dSN) models are a valuable resource for the study of neurotoxicity but are affected by poor replicability and reproducibility, often due to a lack of optimization. Here, we identify experimental factors related to culture conditions that substantially impact cellular drug response in vitro and determine optimal conditions for improved replicability and reproducibility. Treatment duration and cell seeding density were both found to be significant factors, while cell line differences also contributed to variation. A replicable dose–response in viability was demonstrated after 48-h exposure to docetaxel or paclitaxel. Additionally, a replicable dose-dependent reduction in neurite outgrowth was demonstrated, demonstrating the applicability of the model for the examination of additional phenotypes. Overall, we have established an optimized iPSC-dSN model for the study of taxane-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

A 41-year-old man developed rapidly progressive cranial neuropathies and muscle weakness followed by respiratory failure, requiring ventilation support. On examination, there was marked bilateral ptosis and ophthalmoplegia with bulbar, neck and proximal upper limb weakness. He had a recent open left humeral fracture that eventually required amputation. Despite immunoglobulin therapy, his progressive weakness continued. Multiple investigation results were inconclusive. Eventually, botulinum type A toxin was found positive, by which time the therapeutic window for antitoxin had passed. He continued on supportive management and was treated for concomitant infections and nosocomial illnesses. He was subsequently weaned from respiratory support and has made a good neurological recovery. [ABSTRACT FROM AUTHOR]

In this article, we will discuss the history, pharmacodynamics, and neurotoxicity of psychostimulants and hallucinogens. The drugs discussed are widely used and have characteristic toxidromes and potential for neurological injuries with which the practicing clinician should be familiar. Psychostimulants are a class of drugs that includes cocaine, methamphetamine/amphetamines, and cathinones, among others, which produce a crescendoing euphoric high. Seizures, ischemic and hemorrhagic strokes, rhabdomyolysis, and a variety of movement disorders are commonly encountered in this class. Hallucinogens encompass a broad class of drugs, in which the user experiences hallucinations, altered sensorium, distorted perception, and cognitive dysfunction. The experience can be unpredictable and dysphoric, creating a profound sense of anxiety and panic in some cases. Recognizing the associated neurotoxicities and understanding the appropriate management is critical in caring for these patient populations. Several of these agents are not detectable by standard clinical laboratory analysis, making identification and diagnosis an even greater challenge. [ABSTRACT FROM AUTHOR]

With the rise of the opioid epidemic, the practicing neurologist must recognize the patterns of a growing number of opioid-associated neurological injuries. This is in addition to the classic toxidrome of miosis, altered mental status, and respiratory depression, which must never be overlooked, as it is reversible and potentially lifesaving. Several other idiosyncratic syndromes due to opioid-related nervous system insults are defined by their characteristic imaging findings and portend variable functional recovery. Opioid toxicity can not only lead to brain injury, but also spinal cord and, rarely, peripheral nerve injury. As several newer synthetic opioids are undetectable by most assays, a low threshold to suspect opioid exposure must be maintained. [ABSTRACT FROM AUTHOR]

The study objectives are to investigate the ability of capsaicin to revert the toxic effects in glutamate and lipopolysaccharide (LPS)-induced neurotoxicity in Neuro2a (N2a) cells as well as thwarting cognitive impairments, mitochondrial deficits, and oxidative insults induced by 3-nitropropanoic acid (3-NP) in a rodent model of Huntington's disease. In-vitro study with N2a cells was performed through MTT and LDH assay and their biochemical examinations were also performed. 3-NP-administered mice (n = 6) were treated with capsaicin (5, 10, and 20 mg/kg) through the per-oral (p.o.) route for 7 consecutive days. Physiological and behavioral studies were performed in drug-treated mice. After behavioral studies, biochemical parameters were performed for cytokines levels, various oxidative stress parameters, and mitochondrial enzyme complex activities with mitochondrial permeability. N2a cells treated with capsaicin demonstrated neuroprotective effects and reduced neurotoxicity. Based on experimental observation, in an in-vitro study, the effective dose of CAP was 50 µM. Moreover, a 100 µM dose of capsaicin had toxic effects on neuronal cells (N2a cells). On the other hand, the effective dose of 3-NP was 20 mg/kg, (p.o.) in animals (in-vivo). All tested doses of capsaicin upturned the cognitive impairment and motor in-coordination effects induced by 3-NP. 3-NP-injected mice demonstrated substantially increased pro-inflammatory cytokine concentrations, defective mitochondrial complex activity, and augmented oxidative insult. However, capsaicin at different doses reduced oxidative damage and cytokines levels and improved mitochondrial complex activity along with mitochondrial permeability. Furthermore, capsaicin (10 and 20 mg/kg) improved the TNF-α concentration. These findings suggested because of the anti-inflammatory and antioxidant effect, capsaicin can be considered a novel treatment for the management of neurodegenerative disorders by reverting the antioxidant enzyme activity, pro-inflammatory cytokines concentration, and mitochondrial functions. [ABSTRACT FROM AUTHOR]

Purpose: Cefepime is an antibiotic associated with cefepime induced neurotoxicity (CIN), particularly in those with reduced renal function, or in cases of inappropriate medication dosing. This report describes a case of CIN associated with a change in infusion duration from 180 to30 minutes, which to the best of our knowledge has not been previously reported in the literature. Summary: A 73-year old male was treated with extended infusion cefepime over 180 minutes while hospitalized with recurrent pneumonia. On discharge, cefepime was continued as outpatient parenteral antimicrobial therapy (OPAT) administered over 30 minutes. The patient began to experience symptoms of neurotoxicity after 1 day of receiving OPAT, which subsequently led to a readmission as neurological symptoms worsened. Cefepime was discontinued and symptoms resolved within 48 hours. Renal function was stable throughout treatment and no other causes for neurotoxicity were noted. Conclusion: This is a unique case of CIN secondary to shortened infusion time, which is clinically relevant, particularly during transitions of care. Further investigation, including more widespread use of therapeutic drug monitoring will be beneficial to further elucidate the relationship between infusion time and CIN development. [ABSTRACT FROM AUTHOR]

Background: Texture analysis extracts many quantitative image features, offering a valuable, cost-effective, and non-invasive approach for individual medicine. Furthermore, multimodal machine learning could have a large impact for precision medicine, as texture biomarkers can underlie tissue microstructure. This study aims to investigate imaging-based biomarkers of radio-induced neurotoxicity in pediatric patients with metastatic medulloblastoma, using radiomic and dosiomic analysis. Methods: This single-center study retrospectively enrolled children diagnosed with metastatic medulloblastoma (MB) and treated with hyperfractionated craniospinal irradiation (CSI). Histological confirmation of medulloblastoma and baseline follow-up magnetic resonance imaging (MRI) were mandatory. Treatment involved helical tomotherapy (HT) delivering a dose of 39 Gray (Gy) to brain and spinal axis and a posterior fossa boost up to 60 Gy. Clinical outcomes, such as local and distant brain control and neurotoxicity, were recorded. Radiomic and dosiomic features were extracted from tumor regions on T1, T2, FLAIR (fluid-attenuated inversion recovery) MRI-maps, and radiotherapy dose distribution. Different machine learning feature selection and reduction approaches were performed for supervised and unsupervised clustering. Results: Forty-eight metastatic medulloblastoma patients (29 males and 19 females) with a mean age of 12 ± 6 years were enrolled. For each patient, 332 features were extracted. Greater level of abstraction of input data by combining selection of most performing features and dimensionality reduction returns the best performance. The resulting one-component radiomic signature yielded an accuracy of 0.73 with sensitivity, specificity, and precision of 0.83, 0.64, and 0.68, respectively. Conclusions: Machine learning radiomic-dosiomic approach effectively stratified pediatric medulloblastoma patients who experienced radio-induced neurotoxicity. Strategy needs further validation in external dataset for its potential clinical use in ab initio management paradigms of medulloblastoma. [ABSTRACT FROM AUTHOR]

This article explores the relationships among cancer care, financial challenges, and mental health, emphasizing the growing significance of addressing these interconnected issues. Increased frequency of cancer diagnoses and improved treatment options have resulted in higher survival rates, highlighting emerging challenges. Disparities exist among specific populations, underscoring the need for targeted interventions. Current interventions and policy strategies highlight gaps in addressing financial toxicity and health-related quality of life. Future research should include developing tailored interventions and policies that consider the complex interplay among cancer care, financial challenges, and mental health. [ABSTRACT FROM AUTHOR]

Exogenous, well‐established antioxidant N‐acetylcysteine can reduce or prevent the deleterious effects of pesticides. In this study, utilizing a mouse model of daily single dose of N‐acetylcysteine administration, we investigated the impact of this adjuvant on the treatment with atropine and/or obidoxime as well as oxidative stress response in pyrimiphos‐methyl‐induced toxicity. We found that N‐acetylcysteine significantly reduces the oxidative stress generated by pyrimiphos‐methyl. The therapy consisting of atropine and/or obidoxime routinely used in organophosphorous insecticide poisonings, including pyrimiphos‐methyl, had no effect on the antioxidant properties of N‐acetylcysteine. Adjunctive treatment offered by N‐acetylcysteine fills therapeutic gap and may provide the full potential against pyrimiphos‐methyl‐induced toxicity. [ABSTRACT FROM AUTHOR]

Copyright of Abant Medical Journal / Abant Tıp Dergisi is the property of Abant Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Sevoflurane (Sev), a widely used volatile anesthetic, can cause neurotoxicity, and impair learning and memory. Objective This study investigates the role and mechanisms of circHIPK3 in Sev-exposed neurotoxicity and learning and memory impairment. Methods SD rats and hippocampal neuronal cells were exposed to Sev. RT-qPCR analysis of circHIPK3 and miR-338-3p levels. MWM test was performed to examine the behavioral changes in rats. The levels of circHIPK3 and miR-338-3p levels were investigated using RT-qPCR. ELISA assay to analyze the expression of pro-inflammatory factors. CCK-8, flow cytometry, and commercial ROS assay kits were analyzed to detect cell viability, apoptosis, and ROS production. DLR and RIP assays validate circHIPK3 binding to miR-338-3p. Results Sev increased circHIPK3 expression in rat hippocampal tissue as well as in neuronal cells but decreased miR-338-3p levels compared to controls. circHIPK3 binding to miR-338-3p. Furthermore, silencing of circHIPK3 rats attenuated Sev-induced decline in learning and memory functions. silencing circHIPK3 also reduced Sev-induced secretion of inflammatory factors in rat and neuronal cells. Reducing circHIPK3 partially reversed the Sev-induced decrease in cell viability, increased apoptosis, and overproduction of ROS. However, the inhibitory effect of circHIPK3 on Sev neurotoxicity was restored upon downregulation of miR-338-3p. Conclusion Collectively, silencing circHIPK3 alleviates Sev exposure-induced learning and memory deficits and neurotoxicity by enhancing miR-338-3p expression. [ABSTRACT FROM AUTHOR]

It is well established that sevoflurane exposure leads to widespread neuronal cell death in the developing brain. Adenosine deaminase acting on RNA-1 (ADAR1) dependent adenosine-to-inosine (A-to-I) RNA editing is dynamically regulated throughout brain development. The current investigation is designed to interrogate the contributed role of ADAR1 in developmental sevoflurane neurotoxicity. Herein, we provide evidence to show that developmental sevoflurane priming triggers neuronal pyroptosis, apoptosis and necroptosis (PANoptosis), and elicits the release of inflammatory factors including IL-1β, IL-18, TNF-α and IFN-γ. Additionally, ADAR1-P150, but not ADAR1-P110, depresses cellular PANoptosis and inflammatory response by competing with Z-DNA/RNA binding protein 1 (ZBP1) for binding to Z-RNA in the presence of sevoflurane. Further investigation demonstrates that ADAR1-dependent A-to-I RNA editing mitigates developmental sevoflurane-induced neuronal PANoptosis. To restore RNA editing, we utilize adeno-associated virus (AAV) to deliver engineered circular ADAR-recruiting guide RNAs (cadRNAs) into cells, which is capable of recruiting endogenous adenosine deaminases to promote cellular A-to-I RNA editing. As anticipated, AAV-cadRNAs diminishes sevoflurane-induced cellular Z-RNA production and PANoptosis, which could be abolished by ADAR1-P150 shRNA transfection. Moreover, AAV-cadRNAs delivery ameliorates developmental sevoflurane-induced spatial and emotional cognitive deficits without influence on locomotor activity. Taken together, these results illustrate that ADAR1-P150 exhibits a prominent role in preventing ZBP1-dependent PANoptosis through A-to-I RNA editing in developmental sevoflurane neurotoxicity. Application of engineered cadRNAs to rectify the compromised ADAR1-dependent A-to-I RNA editing provides an inspiring direction for possible clinical preventions and therapeutics. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the neurotoxicity and neuroprotective activity of cannabidiol (CBD), valproate, furosemide, metformin, and bilobalide, individually and mixed with CBD in PC12 cells exposed to Glutamate. In addition, antioxidant activity, reactive oxygen species (ROS) production, and caspase-3 activity were evaluated. Methods: Neurotoxicity and neuroprotection were evaluated with the MTT assay; antioxidant activity, and production of ROS with 2,2-diphenyl-1-picryl-hydrazyl-hydrate, and DCFDA methods, respectively; the apoptosis with caspase-3 activity assay. Results: CBD 5 µM, and bilobalide 15.3 µM showed neuroprotective activity by ROS inhibition and decreased caspase-3 activity. Metformin 1548.4 µM did not provide significant neuroprotection but decreased ROS generation. Conclusions: Combining CBD with the study drugs did not improve neuroprotection than the neuroprotection of individual drugs. [ABSTRACT FROM AUTHOR]

Zinc (Zn) and copper (Cu) are essential for normal brain functions. In particular, Zn and Cu are released to synaptic clefts during neuronal excitation. Synaptic Zn and Cu regulate neuronal excitability, maintain calcium (Ca) homeostasis, and play central roles in memory formation. However, in pathological conditions such as transient global ischemia, excess Zn is secreted to synaptic clefts, which causes neuronal death and can eventually trigger the pathogenesis of a vascular type of senile dementia. We have previously investigated the characteristics of Zn-induced neurotoxicity and have demonstrated that low concentrations of Cu can exacerbate Zn neurotoxicity. Furthermore, during our pharmacological approaches to clarify the molecular pathways of Cu-enhanced Zn-induced neurotoxicity, we have revealed the involvement of Ca homeostasis disruption. In the present review, we discuss the roles of Zn and Cu in the synapse, as well as the crosstalk between Zn, Cu, and Ca, which our study along with other recent studies suggest may underlie the pathogenesis of vascular-type senile dementia. [ABSTRACT FROM AUTHOR]

Bupivacaine (BUP) is an anesthetic commonly used in clinical practice that when used for spinal anesthesia, might exert neurotoxic effects. Thioredoxin-interacting protein (TXNIP) is a member of the α-arrestin protein superfamily that binds covalently to thioredoxin (TRX) to inhibit its function, leading to increased oxidative stress and activation of apoptosis. The role of TXNIP in BUP-induced oxidative stress and apoptosis remains to be elucidated. In this context, the present study aimed to explore the effects of TXNIP knockdown on BUP-induced oxidative stress and apoptosis in the spinal cord of rats and in PC12 cells through the transfection of adeno-associated virus-TXNIP short hairpin RNA (AAV-TXNIP shRNA) and siRNA-TXNIP, respectively. In vivo, a rat model of spinal neurotoxicity was established by intrathecally injecting rats with BUP. The BUP + TXNIP shRNA and the BUP + Control shRNA groups of rats were injected with an AAV carrying the TXNIP shRNA and the Control shRNA, respectively, into the subarachnoid space four weeks prior to BUP treatment. The Basso, Beattie & Bresnahan (BBB) locomotor rating score, % MPE of TFL, H&E staining, and Nissl staining analyses were conducted. In vitro, 0.8 mM BUP was determined by CCK-8 assay to establish a cytotoxicity model in PC12 cells. Transfection with siRNA-TXNIP was carried out to suppress TXNIP expression prior to exposing PC12 cells to BUP. The results revealed that BUP effectively induced neurological behavioral dysfunction and neuronal damage and death in the spinal cord of the rats. Similarly, BUP triggered cytotoxicity and apoptosis in PC12 cells. In addition, treated with BUP both in vitro and in vivo exhibited upregulated TXNIP expression and increased oxidative stress and apoptosis. Interestingly, TXNIP knockdown in the spinal cord of rats through transfection of AAV-TXNIP shRNA exerted a protective effect against BUP-induced spinal neurotoxicity by ameliorating behavioral and histological outcomes and promoting the survival of spinal cord neurons. Similarly, transfection with siRNA-TXNIP mitigated BUP-induced cytotoxicity in PC12 cells. In addition, TXNIP knockdown mitigated the upregulation of ROS, MDA, Bax, and cleaved caspase-3 and restored the downregulation of GSH, SOD, CAT, GPX4, and Bcl2 induced upon BUP exposure. These findings suggested that TXNIP knockdown protected against BUP-induced spinal neurotoxicity by suppressing oxidative stress and apoptosis. In summary, TXNIP could be a central signaling hub that positively regulates oxidative stress and apoptosis during neuronal damage, which renders TXNIP a promising target for treatment strategies against BUP-induced spinal neurotoxicity. [Display omitted] Here are 3 highlights of our research: • A significant increase in TXNIP expression was observed in bupivacaine-induced neurotoxicity both in vitro and in vivo. • Bupivacaine exposure activates TXNIP which positively regulates oxidative stress and apoptosis in vitro and in vivo. • Knocking down TXNIP protects against bupivacaine-induced neurotoxicity by inhibiting oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Summary: Methotrexate (MTX), although an indispensable part of contemporary treatment protocols for childhood acute lymphoblastic leukaemia (ALL)/lymphomas (LBL) in improving outcomes, can lead to serious neurotoxicity with long‐term consequences. The aetiopathogenesis, predisposing factors and treatment for MTX‐induced neurotoxicity are not yet well defined. The aim of our study was to detect the incidence, risk factors and to assess the overall outcomes of MTX‐induced neurotoxicity among large cohort of paediatric ALL/LBL patients treated on a uniform protocol. We conducted retrospective audit of medical records of 622 consecutive children (≤14 years) diagnosed with ALL and LBL between January 2018 and December 2022 and treated on modified BFM‐95 protocol at the Department of Pediatric Oncology, Regional Cancer Centre, Thiruvananthapuram. Risk factors predisposing to MTX‐induced neurotoxicity were identified using binary logistic regression analysis. Forty‐three children were diagnosed with MTX‐induced neurotoxicity with an incidence rate of 6.9%. More than two‐thirds of them had high‐grade MTX‐induced neurotoxicity CTCAE v5.0 with a median age of 9 years (range: 9 months to 14 years). Almost half of them developed MTX neurotoxicity during Protocol M followed by Phase‐Ib consolidation (15%). Majority of these patients (84%, 36/43) were challenged again with MTX, with 11% (4/36) developing recurrence. Fifteen per cent had persistent neurological deficits at last follow‐up. Univariate analysis found older age (age > 5 years) (p < 0.001), T‐cell phenotype (p = 0.040), tumour lysis syndrome during induction (p < 0.001), baseline renal problems prior to MTX exposure (p < 0.001) and CNS leukaemic involvement (p < 0.003) to be significantly associated with MTX neurotoxicity. On multivariate analysis, older age (>5 years), tumour lysis during induction and CNS leukaemia retained statistical significance (p < 0.05). Methotrexate‐induced neurotoxicity during paediatric acute lymphoblastic leukaemia/lymphoma therapy is a transient phenomenon in majority and re‐challenge with MTX is generally safe. Older age children who develop tumour lysis during induction and CNS leukaemic involvement are at increased risk for MTX‐induced neurotoxicity during ALL/LBL treatment. [ABSTRACT FROM AUTHOR]

Aims/Objectives: Cisplatin (CIS) is widely used in the treatment of various malignant tumors. The aim of study is to determine the potential protective effects of protocatechuic acid (PCA) on the brain in neurotoxicity induced by CIS in rats.Materials and methods: Forty rats were divided into four groups: 1-Control group: 2- PCA group: PCA was administered orally at a dose of 100 mg/kg/day for 5 weeks. 3-CIS group: 5 mg/kg/week of CIS was administered intraperiteonally 4-PCA + CIS group: The rats were given PCA orally daily for 5 weeks and CIS of 5 mg/kg/week. The brain tissues were used for histopathological examinations and for total antioxidant capacity (TAC), total oxidative state (TOS), oxidative stress index (OSI), tumornecrosis factor-alpha (T NF-α), interleukin 6 (IL-6) Interleukin 1 beta (IL-1β), acetylcholinesterase (AChE), glutamate, gamma aminobutyric acid (GABA), dopamine analyzes in ELISA. WBC, RBC, hemoglobin and hematocrit levels were measured.Results: PCA + CIS group compared to CIS group TOS, OSI, T NF-α, IL-6, IL-1β, AChE, glutamate, WBC levels decreased significantly, while TAC and GABA levels increased statistically significant. With this study, P CA corrected the deterioration in the oxidant / antioxidant status, suppressed neuro-inflammation, decreased AChE activity, partially normalized neurotransmitters, and decreased the increased WBC count. Necrosis seen in the CIS group in histopathological examinations was never seen in the PCA + CIS group.Conclusions: PCA may provide therapeutic benefit when used in conjunction with CIS. [ABSTRACT FROM AUTHOR]

• EEG prior to antigen receptor T-cell (CAR-T) infusion is an additional tool to identify patients at risk of neurotoxicity. • Increased severity and higher incidence of EEG abnormalities after CAR-T infusion indicates the presence of brain dysfunction. • Early EEG in immune effector cell-associated neurotoxicity syndrome may identify patients who require preemptive treatment or close monitoring. Immune effector cell-associated neurotoxicity syndrome (ICANS) is common after chimeric antigen receptor T-cell (CAR-T) therapy. This study aimed to assess the impact of preinfusion electroencephalography (EEG) abnormalities and EEG findings at ICANS onset for predicting ICANS risk and severity in 56 adult patients with refractory lymphoma undergoing CAR-T therapy. EEGs were conducted at the time of lymphodepleting chemotherapy and shortly after onset of ICANS. Twenty-eight (50%) patients developed ICANS at a median time of 6 days after CAR-T infusion. Abnormal preinfusion EEG was identified as a risk factor for severe ICANS (50% vs. 17%, P = 0.036). Following ICANS onset, EEG abnormalities were detected in 89% of patients [encephalopathy (n = 19, 70%) and/or interictal epileptiform discharges (IEDs) (n = 14, 52%)]. Importantly, IEDs seemed to be associated with rapid progression to higher grades of ICANS within 24 h. If confirmed in a large cohort of patients, these findings could establish the basis for modifying current management guidelines, enabling the identification of patients at risk of neurotoxicity, and providing support for preemptive corticosteroid use in patients with both initial grade 1 ICANS and IEDs at neurotoxicity onset, who are at risk of neurological impairment. [ABSTRACT FROM AUTHOR]

Introduction: Tacrolimus-associated neurotoxicity (TAN) manifests with wide clinical spectrum, ranging from mild tremors to severe encephalopathy. The isolated involvement of the brainstem is a rarely documented presentation of TAN, and its clinical and diagnostic characteristics are unclear. Methods: We report two cases of brainstem-isolated TAN (bi-TAN). Moreover, we performed a systematic review of the literature on bi-TAN and extracted data concerning demographics, clinical characteristics, radiological features, and management. The systematic literature search followed PRISMA guidelines and a pre-defined protocol. Results: Eleven patients, including our two, were identified (mean age: 41.3 years, ± 18.8; five males, 45%). Speech disturbance was the most common clinical presentation (45%). The mean latency from Tacrolimus initiation to bi-TAN onset was 26 days (± 30.8). Tacrolimus serum level tested above the reference range in three patients (mean: 26.83 ± 5.48). Brain MRI showed T2-FLAIR hyperintensities; three showed restricted diffusion on ADC maps. Neurological symptoms resolved completely in seven patients (63%) after Tacrolimus withdrawal or dose reduction. Conclusions: Our findings suggest that bi-TAN could represent a brainstem variant of posterior reversible encephalopathy syndrome. Recognition of bi-TAN as a potential cause of isolated brainstem lesions is crucial to disentangle the diagnostic work-up and ensure prompt withdrawal or reduction of the offending agent. [ABSTRACT FROM AUTHOR]

The European Commission asked EFSA to update its 2011 risk assessment on tetrabromobisphenol A (TBBPA) and five derivatives in food. Neurotoxicity and carcinogenicity were considered as the critical effects of TBBPA in rodent studies. The available evidence indicates that the carcinogenicity of TBBPA occurs via non‐genotoxic mechanisms. Taking into account the new data, the CONTAM Panel considered it appropriate to set a tolerable daily intake (TDI). Based on decreased interest in social interaction in male mice, a lowest observed adverse effect level (LOAEL) of 0.2 mg/kg body weight (bw) per day was identified and selected as the reference point for the risk characterisation. Applying the default uncertainty factor of 100 for inter‐ and intraspecies variability, and a factor of 3 to extrapolate from the LOAEL to NOAEL, a TDI for TBBPA of 0.7 μg/kg bw per day was established. Around 2100 analytical results for TBBPA in food were used to estimate dietary exposure for the European population. The most important contributors to the chronic dietary LB exposure to TBBPA were fish and seafood, meat and meat products and milk and dairy products. The exposure estimates to TBBPA were all below the TDI, including those estimated for breastfed and formula‐fed infants. Accounting for the uncertainties affecting the assessment, the CONTAM Panel concluded with 90%–95% certainty that the current dietary exposure to TBBPA does not raise a health concern for any of the population groups considered. There were insufficient data on the toxicity of any of the TBBPA derivatives to derive reference points, or to allow a comparison with TBBPA that would support assignment to an assessment group for the purposes of combined risk assessment. [ABSTRACT FROM AUTHOR]

Periodontitis is associated with various systemic diseases, potentially facilitated by the passage of Porphyromonas gingivalis outer membrane vesicles (Pg-OMVs). Several recent studies have suggested a connection between Pg-OMVs and neuroinflammation and neurodegeneration, but the precise causal relationship remains unclear. This study aimed to investigate the mechanisms underlying these associations using in vitro models. Isolated Pg-OMVs were characterized by morphology, size, and gingipain activity. We exposed SH-SY5Y neuroblastoma cells and BV-2 microglial cells to various concentrations of Pg-OMVs. Cell morphology, a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, an enzyme-linked immunosorbent assay, and Western blot analysis were used to evaluate the cellular mechanism underlying Pg-OMV-induced neurotoxicity in neuronal cells and inflammatory responses in microglial cells. Exposure to Pg-OMVs induced neurotoxicity in SH-SY5Y cells, as evidenced by cellular shrinkage, reduced viability, activation of apoptotic pathways, and diminished neuronal differentiation markers. Gingipain inhibition mitigated these effects, suggesting that gingipain mediates Pg-OMVs-induced neurotoxicity in SH-SY5Y cells. Our research on neuroinflammation suggests that upon endocytosis of Pg-OMVs by BV-2 cells, lipopolysaccharide (LPS) can modulate the production of inducible nitric oxide synthase and tumor necrosis factor-alpha by activating pathways that involve phosphorylated AKT and the phosphorylated JNK pathway. Our study demonstrated that following the endocytosis of Pg-OMVs, gingipain can induce neurotoxicity in SH-SY5Y cells. Furthermore, the Pg-OMVs-associated LPS can trigger neuroinflammation via AKT and JNK signaling pathways in BV-2 cells. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Oncology Nursing Journal is the property of Pappin Communications and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Di‐(2‐ethylhexyl) phthalate (DEHP) is a commonly used plasticizer with known neurotoxic effects. However, the specific mechanism underlying this neurotoxicity remains unclear. This study aimed to investigate the role of lysosomal function and lysophagy in DEHP‐induced neurotoxicity, with a particular focus on the regulatory role of Transcription factor EB (TFEB). To achieve this, we utilized in vitro models of DEHP‐exposed SH‐SY5Y cells and HT22 cells. Our findings revealed that DEHP exposure led to lysosomal damage and dysfunction. Moreover, we observed impaired autophagic degradation, characterized by elevated levels of LC3II and p62. DEHP treatment downregulated the expression of TFEB, GAL3, and TRIM16, while upregulating the expression of PARP. This led to the inhibition of GAL3/TRIM16 axis dependent lysophagy and ultimately excessive apoptosis in neuronal cells. Importantly, TFEB overexpression alleviated lysosomal dysfunction, activated lysophagy, and mitigated DEHP‐induced apoptosis. Overall, our results suggest that DEHP induces not only lysosomal dysfunction, but also inhibits lysophagy through the suppression of GAL3/TRIM16 axis. Consequently, impaired clearance of damaged lysosomes occurs, culminating in neuronal apoptosis. Taken together, our findings highlight the critical role of TFEB in regulating lysophagy and lysosomal function. Furthermore, TFEB may serve as a potential therapeutic target for mitigating DEHP‐induced neuronal toxicity. [ABSTRACT FROM AUTHOR]

Copyright of Online Turkish Journal of Health Sciences (OTJHS) / Online Türk Sağlık Bilimleri Dergisi is the property of Oguz KARABAY and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)