Do Microplastics Have Neurological Implications in Relation to Schizophrenia Zebrafish Models? A Brain Immunohistochemistry, Neurotoxicity Assessment, and Oxidative Stress Analysis.

The effects of exposure to environmental pollutants on neurological processes are of increasing concern due to their potential to induce oxidative stress and neurotoxicity. Considering that many industries are currently using different types of plastics as raw materials, packaging, or distribution pipes, microplastics (MPs) have become one of the biggest threats to the environment and human health. These consequences have led to the need to raise the awareness regarding MPs negative neurological effects and implication in neuropsychiatric pathologies, such as schizophrenia. The study aims to use three zebrafish models of schizophrenia obtained by exposure to ketamine (Ket), methionine (Met), and their combination to investigate the effects of MP exposure on various nervous system structures and the possible interactions with oxidative stress. The results showed that MPs can interact with ketamine and methionine, increasing the severity and frequency of optic tectum lesions, while co-exposure (MP+Met+Ket) resulted in attenuated effects. Regarding oxidative status, we found that all exposure formulations led to oxidative stress, changes in antioxidant defense mechanisms, or compensatory responses to oxidative damage. Met exposure induced structural changes such as necrosis and edema, while paradoxically activating periventricular cell proliferation. Taken together, these findings highlight the complex interplay between environmental pollutants and neurotoxicants in modulating neurotoxicity.

Potential neurotoxicity associated with methotrexate.

This study aimed to elucidate the incidence and characteristics of neurotoxicity in patients receiving methotrexate (MTX) treatment. A retrospective analysis was performed using data from the electronic cohort database spanning from January 1990 to December 2021. This review focused on patients who manifested neurotoxic symptoms post-MTX therapy, excluding patients with peripheral neuropathy. Of the 498 individuals who received MTX, 26 (5.22%) exhibited neurotoxicity. Pediatric patients (< 18 years) accounted for 18 cases (7.44%), whereas adults (> 18 years) comprised eight cases (3.13%). The median onset age was 11 years (range 4-15) in the pediatric cohort and 39.5 years (range 19-67) in the adult cohort. A predominant male predisposition was noted (21 patients, 80.77%). The majority of patients (21, 80.77%) experienced neurotoxic effects following multiple MTX administrations. Modes of MTX delivery included intrathecal (37.0%), intravenous (22.2%), and combined routes (40.7%). Clinical presentations were predominantly encephalopathy (69.2%), followed by encephalomyelopathy (15.4%), myelopathy (11.5%), and polyradiculopathy (3.8%). Fourteen patients recovered (53.85%). Risk factors were male sex, pediatric age (particularly above 10 years), and administration route (intrathecal in adults and intravenous in pediatrics). Although infrequent, MTX-related neurotoxicity has a substantial impact on patient prognosis, with potential development following even a single dose. Its radiological resemblance to diverse neuropathologies, such as cerebral infarction and subacute combined degeneration, necessitates vigilant diagnostic scrutiny.

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.

Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma.

Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count < 150 G/L, a C-reactive protein (CRP) level > 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets (< 150 G/L), use of axi-cel and no bridging therapy or SD/PD after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.

PAHs as environmental pollutants and their neurotoxic effects.

Polycyclic aromatic hydrocarbons (PAHs), which are widely present in incompletely combusted air particulate matter <2.5 µm (PM2.5), tobacco and other organic materials, can enter the human body through various routes and are a class of environmental pollutants with neurotoxic effects. PAHs exposure can lead to abnormal development of the nervous system and neurobehavioral abnormalities in animals, including adverse effects on the nervous system of children and adults, such as a reduced learning ability, intellectual decline, and neural tube defects. After PAHs enter cells of the nervous system, they eventually lead to nervous system damage through mechanisms such as oxidative stress, DNA methylation and demethylation, and mitochondrial autophagy, potentially leading to a series of nervous system diseases, such as Alzheimer's disease. Therefore, preventing and treating neurological diseases caused by PAHs exposure are particularly important. From the perspective of the in vitro and in vivo effects of PAHs exposure, as well as its effects on human neurodevelopment, this paper reviews the toxic mechanisms of action of PAHs and the corresponding prevention and treatment methods to provide a relevant theoretical basis for preventing the neurotoxicity caused by PAHs, thereby reducing the incidence of diseases related to the nervous system and protecting human health.

Identification of differential m6A RNA methylomes and ALKBH5 as a potential prevention target in the developmental neurotoxicity induced by multiple sevoflurane exposures.

Sevoflurane, as a commonly used inhaled anesthetic for pediatric patients, has been reported that multiple sevoflurane exposures are associated with a greater risk of developing neurocognitive disorder. N6-Methyladenosine (m6A), as the most common mRNA modification in eukaryotes, has emerged as a crucial regulator of brain function in processes involving synaptic plasticity, learning and memory, and neurodevelopment. Nevertheless, the relevance of m6A RNA methylation in the multiple sevoflurane exposure-induced developmental neurotoxicity remains mostly elusive. Herein, we evaluated the genome-wide m6A RNA modification and gene expression in hippocampus of mice that received with multiple sevoflurane exposures using m6A-sequencing (m6A-seq) and RNA-sequencing (RNA-seq). We discovered 19 genes with differences in the m6A methylated modification and differential expression in the hippocampus. Among these genes, we determined that a total of nine differential expressed genes may be closely associated with the occurrence of developmental neurotoxicity induced by multiple sevoflurane exposures. We further found that the alkB homolog 5 (ALKBH5), but not methyltransferase-like 3 (METTL3) and Wilms tumor 1-associated protein (WTAP), were increased in the hippocampus of mice that received with multiple sevoflurane exposures. And the IOX1, as an inhibitor of ALKBH5, significantly improved the learning and memory defects and reduced neuronal damage in the hippocampus of mice induced by multiple sevoflurane exposures. The current study revealed the role of m6A methylated modification and m6A-related regulators in sevoflurane-induced cognitive impairment, which might provide a novel insight into identifying biomarkers and therapeutic strategies for inhaled anesthetic-induced developmental neurotoxicity.

Episodes of acute methotrexate-related neurotoxicity linked to compromised long-term neurocognitive function.

Methotrexate is a critical component of curative chemotherapy for pediatric acute lymphoblastic leukemia (ALL), but is associated with neurotoxicity. Information on long-term outcomes following an acute neurotoxic event is limited. Therefore, this report compares neurocognitive performance more than 12 months post diagnosis (mean = 4 years) between ALL patients with (n = 25) and without (n = 146) a history of acute neurotoxicity. Compared to children with no documented on-treatment neurotoxic event, children who experienced a neurotoxic event during treatment exhibited poorer performance on measures of fine motor function (p = .02) and attention (p = .02). Children with ALL who experience acute neurotoxicity may be candidates for early neuropsychological screening and intervention.

Screening tools to evaluate the neurotoxic potential of botanicals: building a strategy to assess safety.

AREAS COVERED: This paper outlines the selection of NAMs, including in vitro assays using primary rat cortical neurons, zebrafish embryos, and Caenorhabditis elegans. These assays aim to assess neurotoxic endpoints such as neuronal activity and behavioral responses. Microelectrode array recordings of rat cortical neurons provide insights into the impact of botanical extracts on neuronal function, while the zebrafish embryos and C. elegans assays evaluate neurobehavioral responses. The paper also provides an account of the selection of botanical case studies based on expert judgment and existing neuroactivity/toxicity information. The proposed battery of assays will be tested with these case studies to evaluate their utility for neurotoxicity screening. EXPERT OPINION: The complexity of botanicals necessitates the use of multiple NAMs for effective neurotoxicity screening. This paper discusses the evaluation of methodologies to develop a robust framework for evaluating botanical safety, including complex neuronal models and key neurodevelopmental process assays. It aims to establish a comprehensive screening framework.

Identification of neural-relevant toxcast high-throughput assay intended gene targets: Applicability to neurotoxicity and neurotoxicant putative molecular initiating events.

The US EPA's Toxicity Forecaster (ToxCast) is a suite of high-throughput in vitro assays to screen environmental toxicants and predict potential toxicity of uncharacterized chemicals. This work examines the relevance of ToxCast assay intended gene targets to putative molecular initiating events (MIEs) of neurotoxicants. This effort is needed as there is growing interest in the regulatory and scientific communities about developing new approach methodologies (NAMs) to screen large numbers of chemicals for neurotoxicity and developmental neurotoxicity. Assay gene function (GeneCards, NCBI-PUBMED) was used to categorize gene target neural relevance (1 = neural, 2 = neural development, 3 = general cellular process, 3 A = cellular process critical during neural development, 4 = unlikely significance). Of 481 unique gene targets, 80 = category 1 (16.6 %); 16 = category 2 (3.3 %); 303 = category 3 (63.0 %); 97 = category 3 A (20.2 %); 82 = category 4 (17.0 %). A representative list of neurotoxicants (548) was researched (ex. PUBMED, PubChem) for neurotoxicity associated MIEs/Key Events (KEs). MIEs were identified for 375 compounds, whereas only KEs for 173. ToxCast gene targets associated with MIEs were primarily neurotransmitter (ex. dopaminergic, GABA)receptors and ion channels (calcium, sodium, potassium). Conversely, numerous MIEs associated with neurotoxicity were absent. Oxidative stress (OS) mechanisms were 79.1 % of KEs. In summary, 40 % of ToxCast assay gene targets are relevant to neurotoxicity mechanisms. Additional receptor and ion channel subtypes and increased OS pathway coverage are identified for potential future assay inclusion to provide more complete coverage of neural and developmental neural targets in assessing neurotoxicity.

Impaired memory in Sprague-Dawley rats exposed to complex groundwater mixtures of contaminants is associated with reduced cranial blood flow and hippocampal neurotoxicity.

Exposure to industrial contaminants has been implicated in neurobehavioral toxicity in humans. To explore this potential risk, we investigated the neurotoxic effects of oral exposure to a complex groundwater mixture containing petroleum hydrocarbons, pesticides, heavy metals, and unknown parent and breakdown products using male and female Sprague Dawley rats. Rats were randomly divided into six groups and orally exposed daily via drinking water to: (i) tap water, (ii) 10 % v/v low impact groundwater, and (iii) 0.01 %, 0.1 %, 1 %, and 10 % high-impact groundwater for 60 days. Medium- and long-term memory (measured using the novel object recognition task) were impaired. However, no gross motor or coordination deficits were observed by the end of the study period (rotarod test). Doppler ultrasound of the middle cerebral and common carotid arteries was performed to examine the hemodynamic changes. The common carotid blood flow decreased in the groundwater-exposed rats compared to that in the control. However, no significant differences in cerebral blood velocity were observed between the exposed and control groups. A significant reduction in hippocampal serotonin levels was observed in groundwater-exposed rats relative to that in the control group. Collectively, these results indicate that impaired recognition memory in rats exposed to groundwater is accompanied by reduced cranial blood flow and hippocampal neurotoxicity, characterized by altered serotonergic signalling. The levels of detected contaminants known to cause neural or vascular damage were of magnitudes lower than the concentrations of contaminants found in the groundwater mixture, meaning the culprit chemical identity remains unknown. This study emphasizes the need to use whole mixture in exposures when dealing with complex contaminated sites rather than the use of individual compounds.

Neurotoxicity assessment of the herbicide pethoxamid in zebrafish (Danio rerio) embryos/larvae.

Pethoxamid, a member of the chloroacetamide herbicide family, is a recently approved chemical for pre- or post-emergence weed control; however, toxicity data for sublethal effects in aquatic organisms exposed to pethoxamid are non-existent in literature. To address this, we treated zebrafish embryos/larvae to pethoxamid over a 7-day period post-fertilization and evaluated several toxicological endpoints associated with oxidative stress and neurotoxicity. Continuous pethoxamid exposure did not affect survival nor hatch success in embryos/larvae for 7 days up to 1000 µg L-1. Exposure to pethoxamid did not affect embryonic ATP-linked respiration, but it did reduce non-mitochondrial respiration at the highest concentration tested. We also noted a significant increase in both apoptosis and levels of reactive oxygen species (ROS) in larvae zebrafish following exposure to pethoxamid. Increases in apoptosis and ROS, however, were not correlated with any altered gene expression pattern for apoptotic and oxidative damage response transcripts. To assess neurotoxicity potential, we measured behavior and several transcripts implicated in neural processes in the central nervous system. While locomotor activity of larval zebrafish was affected by pethoxamid exposure (hyperactivity was observed at concentrations below 1 µg L-1, and hypoactivity was noted at higher exposures to 10 and 100 µg L-1 pethoxamid), there were no effects on steady state mRNA abundance for neurotoxicity-related transcripts tested. This data contributes to knowledge regarding exposure risks for chloroacetamide-based herbicides and is the first study investigating sublethal toxicity for this newly registered herbicide.

Riding the storm: managing cytokine-related toxicities in CAR-T cell therapy.

The advent of chimeric antigen receptor T cells (CAR-T) has been a paradigm shift in cancer immunotherapeutics, with remarkable outcomes reported for a growing catalog of malignancies. While CAR-T are highly effective in multiple diseases, salvaging patients who were considered incurable, they have unique toxicities which can be life-threatening. Understanding the biology and risk factors for these toxicities has led to targeted treatment approaches which can mitigate them successfully. The three toxicities of particular interest are cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effector cell-associated hemophagocytic lymphohistiocytosis (HLH)-like syndrome (IEC-HS). Each of these is characterized by cytokine storm and hyperinflammation; however, they differ mechanistically with regard to the cytokines and immune cells that drive the pathophysiology. We summarize the current state of the field of CAR-T-associated toxicities, focusing on underlying biology and how this informs toxicity management and prevention. We also highlight several emerging agents showing promise in preclinical models and the clinic. Many of these established and emerging agents do not appear to impact the anti-tumor function of CAR-T, opening the door to additional and wider CAR-T applications.

Cefepime Neurotoxicity in Patients With Normal Renal Function: An Overlooked Cause of Encephalopathy in the Intensive Care Unit.

Cefepime is a fourth-generation cephalosporin with extended antimicrobial coverage. Concerns have been raised about the side effects of cefepime including myoclonus, encephalopathy, and seizures, especially when renal impairment is present. There have been reports of cases of adverse neurological consequences despite appropriate renal adjustment. Here, we present a case of a 69-year-old patient initially diagnosed with pneumonia and treated with cefepime. The patient later developed altered mental status, leading to differential diagnoses including stroke, drug overdose, or non-convulsive seizures. Following a comprehensive workup, it was determined that she had cefepime-induced encephalopathy, despite having normal kidney function, which resolved completely after discontinuing the medication. In addition, we include similar cases retrieved from PubMed up to the present date, to the best of our knowledge.

Plasma neurofilament light chain levels in chemotherapy-induced peripheral neurotoxicity according to type of anticancer drug.

BACKGROUND AND PURPOSE: A real-time biomarker in chemotherapy-induced peripheral neurotoxicity (CIPN) would be useful for clinical decision-making during treatment. Neurofilament light chain (NfL) can be detected in blood in the case of neuroaxonal damage. The aim of the study was to compare the levels of plasma NfL (pNfL) according to the type of chemotherapeutic agent and the severity of CIPN. METHODS: This single-center prospective observational longitudinal study included patients treated with paclitaxel (TX; n = 34), brentuximab vedotin (BV; n = 29), or oxaliplatin (PT; n = 19). All patients were assessed using the Total Neuropathy Score-clinical version and Common Terminology Criteria for Adverse Events before, during, and up to 6-12 months after the end of treatment. Nerve conduction studies (NCS) were performed before and after chemotherapy discontinuation. Consecutive plasma samples were analyzed for NfL levels using a Simoa® analyzer. Changes in pNfL were compared between groups and were eventually correlated with clinical and NCS data. Clinically relevant (CR) CIPN was considered to be grade ≥ 2. RESULTS: Eighty-two patients, mostly women (59.8%), were included. One third of the patients who received TX (29.4%), BV (31%), or PT (36.8%) developed CR-CIPN, respectively, without differences among them (p = 0.854). Although pNfL significantly increased during treatment and decreased throughout the recovery period in all three groups, patients receiving TX showed significantly greater and earlier changes in pNfL levels compared to the other agents (p < 0.001). CONCLUSIONS: A variable change in pNfL is observed depending on the type of agent and mechanism of neurotoxicity with comparable CIPN severity, strongly implying the need to identify different cutoff values for each agent.

A zebrafish-based acoustic motor response (AMR) assay to evaluate chemical-induced developmental neurotoxicity.

Behavioral assays using early-developing zebrafish (Danio rerio) offer a valuable supplement to the in vitro battery adopted as new approach methodologies (NAMs) for assessing risk of chemical-induced developmental neurotoxicity. However, the behavioral assays primarily adopted rely on visual stimulation to elicit behavioral responses, known as visual motor response (VMR) assays. Ocular deficits resulting from chemical exposures can, therefore, confound the behavioral responses, independent of effects on the nervous system. This highlights the need for complementary assays employing alternative forms of sensory stimulation. In this study, we investigated the efficacy of acoustic stimuli as triggers of behavioral responses in larval zebrafish, determined the most appropriate data acquisition mode, and evaluated the suitability of an acoustic motor response (AMR) assay as means to assess alterations in brain activity and risk of chemical-induced developmental neurotoxicity. We quantified the motor responses of 120 h post-fertilization (hpf) larvae to acoustic stimuli with varying patterns and frequencies, and determined the optimal time intervals for data acquisition. Following this, we examined changes in acoustic and visual motor responses resulting from exposures to pharmacological agents known to impact brain activity (pentylenetetrazole (PTZ) and tricaine-s (MS-222)). Additionally, we examined the AMR and VMR of larvae following exposure to two environmental contaminants associated with developmental neurotoxicity: arsenic (As) and cadmium (Cd). Our findings indicate that exposure to a 100 Hz sound frequency in 100 ms pulses elicits the strongest behavioral response among the acoustic stimuli tested and data acquisition in 2 s time intervals is suitable for response assessment. Exposure to PTZ exaggerated and depressed both AMR and VMR in a concentration-dependent manner, while exposure to MS-222 only depressed them. Similarly, exposure to As and Cd induced respective hyper- and hypo-activation of both motor responses. This study highlights the efficiency of the proposed zebrafish-based AMR assay in demonstrating risk of chemical-induced developmental neurotoxicity and its suitability as a complement to the widely adopted VMR assay.

Neurotoxicology of dopamine: Victim or assailant?

Since the identification of dopamine as a neurotransmitter in the mid-20th century, investigators have examined the regulation of dopamine homeostasis at a basic biological level and in human disorders. Genetic animal models that manipulate the expression of proteins involved in dopamine homeostasis have provided key insight into the consequences of dysregulated dopamine. As a result, we have come to understand the potential of dopamine to act as an endogenous neurotoxin through the generation of reactive oxygen species and reactive metabolites that can damage cellular macromolecules. Endogenous factors, such as genetic variation and subcellular processes, and exogenous factors, such as environmental exposures, have been identified as contributors to the dysregulation of dopamine homeostasis. Given the variety of dysregulating factors that impact dopamine homeostasis and the potential for dopamine itself to contribute to further cellular dysfunction, dopamine can be viewed as both the victim and an assailant of neurotoxicity. Parkinson's disease has emerged as the exemplar case study of dopamine dysregulation due to the genetic and environmental factors known to contribute to disease risk, and due to the evidence of dysregulated dopamine as a pathologic and pathogenic feature of the disease. This review, inspired by the talk, "Dopamine in Durham: location, location, location" presented by Dr. Miller for the Jacob Hooisma Memorial Lecture at the International Neurotoxicology Association meeting in 2023, offers a primer on dopamine toxicity covering endogenous and exogenous factors that disrupt dopamine homeostasis and the actions of dopamine as an endogenous neurotoxin.

Catatonia Due to Lithium Neurotoxicity: A Case Report. / Lityum Nörotoksisitesine Ikincil Gelisen Katatoni Vakasi: Bir Olgu Sunumu.

Lithium may cause toxicity as it has a narrow therapeutic range. Lithium intoxication may manifest in the form of acute, acute on chronic and chronic intoxication. Neurotoxicity is a common component of chronic lithium intoxication and the symptoms include tremor, ataxia, dysarthria, extrapyramidal symptoms, hyperreflexia, seizures and status epilepticus. Although rare, catatonia could as a manifestation of lithium neurotoxicity. In this report, we present a patient with bipolar disorder presenting with catatonic symptoms secondary to lithium intoxication. We will discuss the risk factors, differential diagnosis and the treatment of catatonic symptoms. Lithium neurotoxicity may present with various clinical symptoms including catatonia, and differential diagnosis should be made well in such cases. If lithium neurotoxicity is suspected, rapid and appropriate intervention is required to prevent permanent neurological damage. Keywords: Lithium, Neurotoxicity, Catatonia.

Ion Channel and Transporter Involvement in Chemotherapy-Induced Peripheral Neurotoxicity.

The peripheral nervous system can encounter alterations due to exposure to some of the most commonly used anticancer drugs (platinum drugs, taxanes, vinca alkaloids, proteasome inhibitors, thalidomide), the so-called chemotherapy-induced peripheral neurotoxicity (CIPN). CIPN can be long-lasting or even permanent, and it is detrimental for the quality of life of cancer survivors, being associated with persistent disturbances such as sensory loss and neuropathic pain at limb extremities due to a mostly sensory axonal polyneuropathy/neuronopathy. In the state of the art, there is no efficacious preventive/curative treatment for this condition. Among the reasons for this unmet clinical and scientific need, there is an uncomplete knowledge of the pathogenetic mechanisms. Ion channels and transporters are pivotal elements in both the central and peripheral nervous system, and there is a growing body of literature suggesting that they might play a role in CIPN development. In this review, we first describe the biophysical properties of these targets and then report existing data for the involvement of ion channels and transporters in CIPN, thus paving the way for new approaches/druggable targets to cure and/or prevent CIPN.

Neurotoxic snakebites in Africa: Clinical implications, therapeutic strategies, and antivenom efficacy.

Snakebite is a significant health concern in Africa, particularly due to neurotoxic envenomation which can lead to neuromuscular paralysis and respiratory failure. In Nigeria, snakes from the Elapidae family are a notable cause of envenomation cases, though these incidents are underreported. This review examined case reports of neurotoxic envenomation in Africa, highlighting the clinical impacts and the efficacy of available antivenoms. Preclinical studies showed that the polyvalent antivenom from the South African Institute for Medical Research (SAIMR) was highly effective against neurotoxicity with a protective efficacy (R) of 1346.80 mg/mL, while clinical assessment emphasized the need for high-dose antivenom therapy along with supportive measures like mechanical ventilation. Unlike hemorrhagic envenomation, where antivenom promptly resolves bleeding, neurotoxic cases often require additional interventions. The review underscores the necessity for tailored approaches in antivenom therapy to address the complexities of neurotoxic snakebites and reduce their public health burden in Africa.

Neurotoxicity and Developmental Neurotoxicity of Copper Sulfide Nanoparticles on a Human Neuronal In-Vitro Test System.

Nanoparticles (NPs) are becoming increasingly important novel materials for many purposes, including basic research, medicine, agriculture, and engineering. Increasing human and environmental exposure to these promising compounds requires assessment of their potential health risks. While the general direct cytotoxicity of NPs is often routinely measured, more indirect possible long-term effects, such as reproductive or developmental neurotoxicity (DNT), have been studied only occasionally and, if so, mostly on non-human animal models, such as zebrafish embryos. In this present study, we employed a well-characterized human neuronal precursor cell line to test the concentration-dependent DNT of green-manufactured copper sulfide (CuS) nanoparticles on crucial early events in human brain development. CuS NPs turned out to be generally cytotoxic in the low ppm range. Using an established prediction model, we found a clear DNT potential of CuS NPs on neuronal precursor cell migration and neurite outgrowth, with IC50 values 10 times and 5 times, respectively, lower for the specific DNT endpoint than for general cytotoxicity. We conclude that, in addition to the opportunities of NPs, their risks to human health should be carefully considered.