Register or Submit a manuscript.
Quick Link
OBM Neurobiology

(ISSN 2573-4407)

OBM Neurobiology is an international peer-reviewed Open Access journal published quarterly online by LIDSEN Publishing Inc. By design, the scope of OBM Neurobiology is broad, so as to reflect the multidisciplinary nature of the field of Neurobiology that interfaces biology with the fundamental and clinical neurosciences. As such, OBM Neurobiology embraces rigorous multidisciplinary investigations into the form and function of neurons and glia that make up the nervous system, either individually or in ensemble, in health or disease. OBM Neurobiology welcomes original contributions that employ a combination of molecular, cellular, systems and behavioral approaches to report novel neuroanatomical, neuropharmacological, neurophysiological and neurobehavioral findings related to the following aspects of the nervous system: Signal Transduction and Neurotransmission; Neural Circuits and Systems Neurobiology; Nervous System Development and Aging; Neurobiology of Nervous System Diseases (e.g., Developmental Brain Disorders; Neurodegenerative Disorders).

OBM Neurobiology publishes a variety of article types (Original Research, Review, Communication, Opinion, Comment, Conference Report, Technical Note, Book Review, etc.). Although the OBM Neurobiology Editorial Board encourages authors to be succinct, there is no restriction on the length of the papers. Authors should present their results in as much detail as possible, as reviewers are encouraged to emphasize scientific rigor and reproducibility.

Publication Speed (median values for papers published in 2025): Submission to First Decision: 10.3 weeks; Submission to Acceptance: 17.1 weeks; Acceptance to Publication: 8.0 days (1-2 days of FREE language polishing included)
Current Issue: 2026  Archive: 2025 2024 2023 2022 2021 2020 2019 2018 2017
Open Access Review

Exposure to Environmental Toxicants: Glymphatic System Dysfunction and Its Implications on Neurodevelopmental Disorders

Mojtaba Ehsanifar 1,* ORCID logo, Akram Gholami 2, Reyhaneh Shenasi 3, Nioosha Pahnavar 2, Maryam Golmohammadi 2

  1. Department of Environmental Health, Torbat Jam Faculty of Medical Sciences, Torbat Jam, Iran

  2. Department of Nursing, Torbat Jam Faculty of Medical Sciences, Torbat Jam, Iran

  3. Department of Public Health, Torbat Jam Faculty of Medical Sciences, Torbat Jam, Iran

* Correspondence: Mojtaba Ehsanifar ORCID logo

Academic Editor: Fabrizio Stasolla

Received: October 30, 2025 | Accepted: April 20, 2026 | Published: April 27, 2026

OBM Neurobiology 2026, Volume 10, Issue 2, doi:10.21926/obm.neurobiol.2602333

Recommended citation: Ehsanifar M, Gholami A, Shenasi R, Pahnavar N, Golmohammadi M. Exposure to Environmental Toxicants: Glymphatic System Dysfunction and Its Implications on Neurodevelopmental Disorders. OBM Neurobiology 2026; 10(2): 333; doi:10.21926/obm.neurobiol.2602333.

© 2026 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.

Abstract

The glymphatic system is a glia-dependent network surrounding blood vessels that facilitates the exchange of cerebrospinal fluid (CSF) and interstitial fluid, playing a crucial role in clearing neuro-metabolites from the brain. This system’s efficiency in transporting waste significantly increases during non-rapid eye movement non-REM sleep. Recent findings suggests that malfunctioning of the glymphatic system might be linked to neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and schizophrenia (SCZ), all of which often correlate with disturbed sleep patterns. Furthermore, various environmental toxicants have been shown to affect neurodevelopment negatively. Exposure to these toxicants early in life disrupts the sleep/Blood-Brain Barrier (BBB)/Aquaporin-4 connections, impairs the glymphatic system’s ability to clear substances like amyloid-beta (Aβ), tau proteins, and inflammatory mediators, ultimately skewing neurodevelopment toward an increased risk of disorders. In summary, this narrative review consolidates existing evidence. It highlights key priorities for examining the relationship between the exposome, the glymphatic system, and neurodevelopmental pathways, aiming to pave the way for future research and therapeutic interventions.

Keywords

Environmental toxicants exposure; glymphatic system; neurodevelopmental disorders

1. Introduction

Neurodevelopmental disorders encompass a group of clinical conditions that appear in early developmental stages, marked by difficulty in personal, social, academic, or occupational areas, as identified by the American Psychiatric Association in 2022. Among these disorders, Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are the most common [1]. Although not officially classified under neurodevelopmental disorders by the DSM-5-TR, a growing body of evidence points to the neurodevelopmental roots of schizophrenia, corresponding conceptually with this group [2,3]. High prevalence of comorbidities is a shared characteristic of all neurodevelopmental disorders [4,5]. The diverse clinical presentations and complex pathophysiologies of neurodevelopmental conditions pose significant hurdles for early diagnosis and treatment [6]. Over 200 high-risk genes have been identified, influencing critical biological processes like synaptic function, transcriptional regulation, and epigenetic mechanisms [7]. Environmental factors are also critical in the emergence and progression of neurodevelopmental disorders, acting through oxidative stress, neuroinflammation, and epigenetic modifications, which ultimately result in structural and functional changes in the brain [8,9,10]. The interplay between genes and environment underscores why individuals with genetic predispositions are more susceptible to environmental hazards. Hence, the concept of the exposome—the collected environmental exposures throughout a person’s life and their impact on brain health—has gained significance [11,12]. Toxic heavy metals are well documented for their ability to disrupt enzymatic functions, modify cell signaling, induce neuroinflammation, and foster oxidative stress, linking them to neurodevelopmental disorders [13,14]. The study of the glymphatic system is a comparatively new frontier in scientific inquiry, having been proposed only in 2012 and experiencing notable advancements starting around 2015 [15]. The glymphatic system has become a focal point as a major pathway connecting environmental impacts to neurodevelopmental consequences. It manages waste removal via cerebrospinal fluid (CSF) directed from the subarachnoid space into the brain’s interstitium through astrocytic aquaporin-4 channels along perivascular spaces. The CSF moves into perivenous spaces and meningeal lymphatic routes, eventually reaching cervical lymph nodes, predominantly during sleep, which enhances glymphatic clearance [16,17]. A dysfunctional glymphatic system can compromise protein clearance, lead to the build-up of misfolded proteins, and alter neuroinflammatory responses [18,19]. This suggests it may act as a unifying mechanism between toxic exposures and susceptibility to neurodevelopmental disorders. This mini-review aims to synthesize empirical evidence on the interconnections between environmental toxins, glymphatic system dysfunction, and neurodevelopmental disorders, examining shared biological processes and evaluating potential intervention strategies.

2. Neurodevelopmental Disorders and Glymphatic System Dysfunction

The link between the glymphatic system and neurodevelopmental disorders like ASD, ADHD, and SCZ is gaining significant focus [20,21]. Specifically, in autism spectrum disorder (ASD), studies have shown consistent changes in perivascular spaces (PVS). Enlargement of these spaces can be observed as early as 24 months, correlating with a higher likelihood of ASD diagnosis and more severe symptoms such as verbal dysfunction and sleep issues [22,23]. Furthermore, increased volumes of extra-axial cerebrospinal fluid in children aged 6 to 24 months indicate a potential relationship between PVS dilation and impaired glymphatic function early in life [24,25]. Sex differences in ASD are noted, with boys showing greater PVS volume in the white matter than girls, which is linked to insomnia [26]. Advanced imaging approaches such as diffusion tensor imaging along the perivascular space (DTI-ALPS) support the notion of glymphatic dysfunction in ASD, showing lower values than in healthy individuals [23]. The DTI-ALPS index tends to increase with age, suggesting a decline in glymphatic function over time [27]. Comparing individuals with ASD to those with ADHD using both DTI-ALPS and diffusion kurtosis imaging (DKI-ALPS) has revealed a reduced index in ASD, which correlates with higher severity and worse developmental outcomes [22,23]. The DKI-ALPS is more sensitive for detecting alterations in the glymphatic system [28]. ADHD findings show increased PVS volume and changes in CSF diffusivity in children compared to their non-ADHD peers [29]. Furthermore, reduced DTI-ALPS values are linked to inattention symptoms and, in adults, correlate with poor visual memory performance [21]. This highlights persistent glymphatic issues in ADHD across the lifespan, potentially tied to cognitive deficits. Schizophrenia (SCZ) follows a similar pattern, with reduced DTI-ALPS values linked to cognitive difficulties, particularly in visuospatial, attention, and orientation domains [30]. A study has shown a connection among DTI-ALPS, cognitive performance, and gut microbiota composition, pointing to a potential gut-brain axis in this context [31]. Markers like PVS changes and extra-axial CSF can serve as early indicators in ASD, ADHD, and SCZ, aiding earlier diagnosis [29,32]. Recent findings support the idea that childhood PVS enlargement indicates impaired CSF circulation with potential consequences for neurodevelopment and long-term cognitive outcomes [24]. These findings collectively highlight the role of sleep-dependent glymphatic dynamics as a potential mechanism linking inflammation, BBB integrity, and solute clearance in neurodevelopmental disorders.

3. Hazards of Environmental Toxicants

The primary categories of hazardous substances include heavy metals, pesticides, hydrocarbons, solvents, radioactive elements, and improperly disposed pharmaceuticals and cosmetics [33]. Approximately 7 million deaths yearly are linked to global environmental pollution, as reported by Rentschler and Leonova [34]. The detrimental impact of conventional toxicants like pesticides is well-documented in scientific research, posing significant risk factors for developing malignant tumors [35,36]. Studies confirm that agricultural workers exposed to chemicals like glyphosate and atrazine exhibit increased cancer incidences. Moreover, communities near farming areas demonstrate similar health concerns. Research findings highlight notable links between pesticide exposure and enhanced risks of non-Hodgkin’s lymphoma, leukemia, and bladder cancer [37,38].

3.1 Exposure to Microplastics and Nanoplastics

New findings have identified additional hazardous substances that affect both the environment and human health, including microplastics (MP) and nanoplastics (NP) [39]. MPs are categorized as primary, originating from personal care products like exfoliants and toothpaste, and as secondary, resulting from the breakdown of larger plastics—the latter posing greater health hazards [39,40]. Exposure to MPs occurs through diverse pathways, including ingestion via contaminated food, inhalation, and dermal contact [23]. Notably, ingestion is primarily linked to water pollution and bioaccumulation of pollutants in marine life consumed by humans [41,42]. Meanwhile, inhalation exposure can occur from atmospheric MPs emitted by sources such as automotive tire wear [43,44,45]. Dermal contact is particularly associated with NPs in personal care products [46,47]. The interaction of MPs and NPs with the human body can disrupt various physiological systems, causing oxidative stress, activating inflammatory pathways, and inducing toxicity at both cellular and neurological levels [23,40,48]. Animal studies show that prenatal exposure to MPs can alter neurotransmitter levels in the brain, reduce cortical layer thickness, and lead to anxiety and memory deficits, indicating potential interference with crucial brain development [49].

3.2 Exposure to Endocrine Disrupting Chemicals

In conjunction with pesticides and microplastics, numerous toxic substances have been shown to affect multiple physiological systems and disrupt critical biological functions necessary for maintaining homeostasis, including gametogenesis and pregnancy. Among these substances, endocrine-disrupting chemicals (EDCs) are particularly significant, as they interfere with hormonal signaling, leading to abnormal endocrine system function [50]. Research indicates that EDCs, such as heavy metals, polyfluoroalkyl substances (PFAS), bisphenols (BPs), and parabens, can reduce sperm motility and volume in men [51]. In women, these EDCs can cross the placental barrier, leading to bioaccumulation in the fetus [52]. The consequences of these alterations include negative effects on reproductive and neurodevelopment, and an increased risk of prematurity [53].

3.3 Emerging Pollutants

With modernization and industrialization, the risk of exposure to emerging pollutants has inevitably increased. Emerging pollutants are substances that are not yet subject to relevant management policies or emission control standards, but are likely to be included in the controlled object based on their frequency of detection and potential health risks [54]. Emerging pollutants have been newly discovered in the environment or, if previously known, have only recently come to attention [55]. Emerging pollutants are usually characterized by serious hazards, hidden risks, environmental persistence, bioaccumulation, extensive sources, and complex management [56]. Emerging pollutants that have recently attracted widespread international concern are broadly divided into three categories: endocrine-disrupting chemicals (EDCs), persistent organic pollutants (POPs), and pharmaceutical and personal care products (PPCPs), with overlap among them. Exposure assessment studies of emerging pollutants often rely on structural models because these pollutants are difficult to observe directly, and the mechanisms and manifestations in the body after exposure are complex [52,57]. Some risks associated with exposure to emerging pollutants are shown in Figure 1. Among newer contaminants, PFAS have shown potential in affecting neurodevelopment, though more evidence is needed to tighten the connection between PFAS and ASD [58]. Findings suggest detrimental impacts on cognitive functions in children, with boys showing particular susceptibility to these influences [59].

Click to view original image

Figure 1 Emerging Pollutants Risks.

4. Health Effects of Environmental Toxicants

4.1 Immune System Imbalances

Toxicants are also linked to immune system imbalances. One study examined the consequences of exposure to environmental pollutants on systemic and airway inflammation and altered modulation of the immune response. Cytokines like IL-8, IL-6, IL-1, IL-4, and TNFα were identified as stable biomarkers, along with nitric oxide and CD4/CD8 immune markers [60]. Additionally, epigenetic changes, including DNA methylation modifications and histone alterations, were observed. Another study focused on an animal model exposed dermally to PFAS, noting reduced populations of B cells, NK cells, and macrophages in the spleen, along with increased CD4+ and CD8+ T lymphocytes in the dermis, indicating an attenuated humoral immune response [61]. Similarly, children living in high-pollution areas showed reduced B lymphocyte counts and serum C3/C4 levels, with increased monocyte counts and proportions of CD8+ T lymphocytes, suggesting immunosuppression and an associated inflammatory adaptation [62].

4.2 Maternal Immune Activation Theory

The maternal immune activation (MIA) theory suggests that systemic inflammation during pregnancy—often due to infection or inflammatory insults—alters the intrauterine environment (cytokines, fetal microglia, placenta–brain axis), leading to reprogramming of neurodevelopment and increased risks for neurodevelopmental disorders like ASD and ADHD [63,64].

4.3 Impact on the CNS

Beyond peripheral effects, various toxicants have significant impacts on the central nervous system (CNS). Recent research links air pollution to oxidative stress, inflammation, and BBB impairment, all of which contribute to the onset of neurological disorders [65,66,67,68]. New findings suggest that both direct and indirect exposure to toxins affect neurodevelopment. Nonetheless, isolating their effects within individual biological systems is challenging due to pleiotropy, complex exposure mixtures, variations in developmental windows of susceptibility, and context-dependent interactions.

4.3.1 Environmental Pollutants, the Glymphatic System, and Neurodevelopment

Environmental pollutants have wide-ranging health implications, but their impact on the brain is especially significant. Research consistently reveals connections between exposure to various pollutants during pregnancy and childhood and the onset of neurodevelopmental disorders.

Research illustrates that fine particulate matter, particularly PM2.5, is positively correlated with several neurodevelopmental issues. For instance, PM2.5 has been linked to ADHD. ASD association stands at an OR of 1.10 (95% CI: 1.04 to 1.17). Schizophrenia (SCZ) correlations, as indicated by biological aging markers, highlight changes in serum glycerophospholipid metabolites. Moreover, PM2.5 exposure has been linked to changes in gut microbiota [69]. There is a noted link between prenatal O3 exposure and the development of ASD. Evidence points to an association between NO2 exposure and both ASD and broader neurodevelopmental challenges. Persistent associations between Benzene and Nickel and ADHD have been noted [70].

4.3.2 Toxicants and the Glymphatic System

Within this scope, while the precise influence of toxicants on the glymphatic system remains to be fully elucidated, there is already evidence that various pesticides and herbicides, including glyphosate and rotenone, interact with mechanisms pertinent to glymphatic system function. Intriguingly, experiments have demonstrated that glyphosate, at varying doses, can breach the blood-brain barrier and accumulate in the mouse brain in vivo. Additionally, glyphosate exposure in vitro has increased Aβ40-42 production and diminished cell viability in primary cortical neurons. These findings align with the theory that glyphosate could provoke neuroinflammation, thereby contributing to alterations associated with neurodegenerative diseases [71]. Conversely, rotenone has been robustly associated with pathological changes and clinical manifestations similar to those observed in Parkinson’s disease patients, such as the development of α-synuclein aggregates in neurons and inflammatory shifts [72]. Recent research on rotenone-induced Parkinson’s disease has revealed that this neurotoxin markedly diminished the influx of Texas-Red Dextran 40 kDa and fluorescein isothiocyanate tracers into the brain following a cisternal injection, while significantly heightening tracer retention within the brain parenchyma. Collectively, these results suggest a functional impairment of the glymphatic system following pesticide exposure [73]. Moving the focus from pesticides to another toxic substance, polystyrene nanoplastics have been shown to impair glymphatic system function in preclinical research considerably. A recent study involving intranasal delivery of this compound in mice resulted in increased brain bioaccumulation, heightened levels of Aβ and p-Tau proteins, disruption of polarized astrocytic aquaporin-4 expression in astrocytic endfeet, induction of neuroinflammation, and eventual cognitive impairment [74].

5. Potential Therapeutic Interventions

Understanding how the glymphatic system functions at the intersection of neurodevelopmental disorders and environmental toxin exposure opens the door to developing new therapeutic approaches. Dysfunction of the glymphatic system, often tied to oxidative stress, neuroinflammation, and BBB impairment, as noted by various studies [18,75], suggests that targeting this system could yield significant therapeutic benefits. Evidence suggests that physical activity-based interventions can positively influence glymphatic function. In APP/PS1 transgenic mice, swimming exercise increased astrocytic aquaporin-4 expression and promoted its polarization at the ends of perivascular astrocytes, thereby decreasing Aβ plaque formation [76]. Similarly, another study using an animal model found that voluntary circular exercise promoted glymphatic clearance of Aβ, increased astrocytic aquaporin-4 polarization, and improved cognitive deficits and anxiety-related behaviors [77]. Although these models are linked to neurodegenerative diseases, a connection between Aβ deposition and toxicant exposure in neurodevelopmental disorders is plausible, as these conditions share similar pathophysiological features [27].

6. Pharmacological Interventions

Recent studies highlight certain drugs with potential effects on the glymphatic system. Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, has been shown to lower pro-inflammatory cytokines and prevent neuronal apoptosis [78]. In a related animal study, dexmedetomidine increased CSF flow and reduced the risk of accumulation of metabolic waste products [79]. Similarly, when administered in an intracerebral hemorrhage model, simvastatin restored the glymphatic system’s integrity through the VEGF-C/VEGFR3/PI3K-Akt pathway [80]. Another study in the same model showed that melatonin had a neuroprotective effect, enhancing glymphatic transport recovery and preventing BBB impairment [81].

7. Mitigating Toxicant Effects

The negative impact of toxic substances on the brain can be mitigated with specific antioxidant, anti-inflammatory, and chelating agents that reduce toxin burdens and safeguard neurovascular integrity. Experimental findings have demonstrated that combining deferiprone with N-acetylcysteine entirely reversed brain dysfunction caused by iron overload by restoring the BBB, mitochondrial function, and synaptic plasticity [82]. Moreover, advances in nanotechnology, such as the use of liposomes, exosomes, and dendrimers for the delivery of anti-inflammatory agents to the brain, offer promise [83]. These nanocarriers aim to reduce neuroinflammation, offering an innovative approach to mitigating the effects of environmental toxicants on the CNS.

8. Limitations and Future Directions in Glymphatic Research

In our examination, we attempt to outline how the glymphatic system’s operation and structure might be associated with neurodevelopmental disorders such as ASD, SCZ, and ADHD, particularly considering the influence of environmental toxicants in these processes. Nevertheless, to date, only a limited number of investigations have thoroughly explored this potential relationship. Even with the noteworthy escalation in research publications in recent years, this domain is still in its developmental stages, necessitating further original studies to solidify its translational potential [15]. Furthermore, the complexity and multifactorial nature of neurodevelopmental disorders remain an enigma, further complicating efforts to elucidate their relationship to environmental toxicant exposure and glymphatic system function.

9. Comprehensive Findings on Environmental Toxicants

Current studies underscore the crucial role of the glymphatic system in clearing the brain of metabolites generated by neuroinflammatory and oxidative stress responses. Based on this understanding, we propose a broader investigational scope beyond traditional mechanisms, emphasizing the potential modulation of glymphatic system efficacy in neurodevelopmental disorders by extensive environmental exposure spanning progenitors’ lifetimes, and during gestation, as well as the exacerbation of symptoms in patients with these disorders.

Various environmental toxicants have been linked to unfavorable neurodevelopment, including fine particulate matter (PM2.5), other air pollutants like ozone (O3) and nitrogen dioxide (NO2), metals (such as lead with mixed findings for mercury), PFAS, pesticides (like glyphosate), heavy metals (including methylmercury and lead), and nanoplastics. Preclinical findings suggest potential mechanistic pathways by which these pollutants interfere with the BBB, disrupt astrocytic aquaporin-4 polarization at astrocytic end feet, impair the exchange of cerebrospinal fluid and interstitial fluid, and heighten neuroinflammation—culminating in glymphatic dysfunction.

Overall, this body of research suggests that various environmental toxicants can significantly influence brain physiology and development, presenting notable links with both neurodevelopmental disorders and the glymphatic system. Although no research has directly examined the effects of toxicants on the glymphatic system in the context of neurodevelopmental disorders, a hypothesis holds that early-life exposure to toxicants may elevate the risk of glymphatic dysfunction and subsequent neurodevelopmental issues.

10. Future Directions and Research Recommendations

Early-life environmental exposures disrupt crucial axes, such as the BBB and astrocytic aquaporin-4, thereby hindering the glymphatic system’s clearance of solutes like amyloid-beta, tau, and inflammatory mediators. This can skew neurodevelopmental trajectories, elevating the risk of heightened conditions in patients with neurodevelopmental disorders. To rigorously examine this proposition, future research must blend exposome evaluations with glymphatic system-specific neuroimaging (e.g., DTI-/DKI-ALPS), cerebrospinal fluid biomarkers, and tangible sleep metrics. Studies should be designed to differentiate by disorder subtypes and developmental stages.

Noteworthy evidence gaps persist, including the lack of focused studies testing toxicant impacts on the glymphatic system in neurodevelopmental disorder populations, limited longitudinal study designs spanning sensitive periods, insufficient attention to sex differences and exposure mixtures, and the absence of glymphatic system endpoints amenable to translation. The intersection of the glymphatic system, toxicants, and neurodevelopment represents an exciting yet underexplored field. Addressing these gaps could enhance our understanding of disease mechanisms, fostering novel prevention and therapeutic strategies and providing pathways for new approaches.

11. Conclusion

In summary, research corroborates substantial links between environmental toxicants and several neurodevelopmental disorders. This connection underscores the critical importance of minimizing exposure, especially during early developmental stages. Consistent with this perspective, dysregulation of the glymphatic system may provide a mechanistic connection between environmental toxicant exposure and the onset or progression of neurodevelopmental disorders. By integrating strategies targeting the glymphatic system with preventive actions and toxicant protection, a promising approach for treating and managing neurodevelopmental disorders can be developed.

Abbreviations

Acknowledgments

This work was supported by Dr. Ehsanifar research lab.

Author Contributions

ME Conceptualization, Supervision and Writing – original draft – review & editing; AGH and NP and RSH and MG Writing – review & editing. All authors have read and agreed to the published version of the manuscript.

Funding

None of the funding sources had any role in the study design, in the writing of the manuscript, or in the decision to submit the article for publication.

Competing Interests

All the authors declare that there are no conflicts of interest.

Data Availability Statement

No data was used for the research described in the article.

AI-Assisted Technologies Statement

No Generative Artificial intelligence (AI) was used in the preparation of this manuscript and AI tools were used solely for basic grammar correction and language refinement in the preparation of this manuscript. Specifically, OpenAI’s ChatGPT was employed to improve the readability and linguistic clarity of the English text. All scientific content, data interpretation, and conclusions were developed independently by the authors. The authors accept full responsibility for the content of the manuscript.

References

  1. Bertollo AG, Puntel CF, da Silva BV, Martins M, Bagatini MD, Ignácio ZM. Neurobiological relationships between neurodevelopmental disorders and mood disorders. Brain Sci. 2025; 15: 307. [CrossRef] [Google scholar]
  2. Bowler A, Arichi T, Austerberry C, Fearon P, Ronald A. A systematic review and meta-analysis of the associations between motor milestone timing and motor development in neurodevelopmental conditions. Neurosci Biobehav Rev. 2024; 167: 105825. [CrossRef] [Google scholar]
  3. Bhuiyan MN, Saha BK, Satter MA. Harnessing artificial intelligence and precision diets for brain health and cognitive resilience. J Nutr. 2025; 155: 3179-3190. [CrossRef] [Google scholar]
  4. Khachadourian V, Mahjani B, Sandin S, Kolevzon A, Buxbaum JD, Reichenberg A, et al. Comorbidities in autism spectrum disorder and their etiologies. Transl Psychiatry. 2023; 13: 71. [CrossRef] [Google scholar]
  5. Danielson ML, Claussen AH, Bitsko RH, Katz SM, Newsome K, Blumberg SJ, et al. ADHD prevalence among US children and adolescents in 2022: Diagnosis, severity, co-occurring disorders, and treatment. J Clin Child Adolesc Psychol. 2024; 53: 343-360. [CrossRef] [Google scholar]
  6. Nikanfar M, Avci CB, Khalilnezhad A, Shahriyari E, Nourazarian A. Brain-derived exosomes in neurodevelopmental and neuropsychiatric disorders: Molecular insights, therapeutic potential, and translational challenges. Mol Neurobiol. 2025; 62: 16342-16382. [CrossRef] [Google scholar]
  7. Gao S, Shan C, Zhang R, Wang T. Genetic advances in neurodevelopmental disorders. Med Rev. 2025; 5: 139-151. [CrossRef] [Google scholar]
  8. Ehsanifar M, Yavari Z, Rafati M. Exposure to urban air pollution particulate matter: Neurobehavioral alteration and hippocampal inflammation. Environ Sci Pollut Res. 2022; 29: 50856-50866. [CrossRef] [Google scholar]
  9. Ehsanifar M, Tameh AA, Farzadkia M, Kalantari RR, Zavareh MS, Nikzaad H, et al. Exposure to nanoscale diesel exhaust particles: Oxidative stress, neuroinflammation, anxiety and depression on adult male mice. Ecotoxicol Environ Saf. 2019; 168: 338-347. [CrossRef] [Google scholar]
  10. Ehsanifar M, Montazeri Z, Zavareh MS, Rafati M, Wang J. Cognitive impairment, depressive-like behaviors and hippocampal microglia activation following exposure to air pollution nanoparticles. Environ Sci Pollut Res. 2023; 30: 23527-23537. [CrossRef] [Google scholar]
  11. Ehsanifar M, Gholami A, Pahnavar N, Shenasi R, Golmohammadi M. Exposure to mycotoxins: Neurological disorders and psychiatric manifestations. OBM Neurobiol. 2026; 10: 322. [CrossRef] [Google scholar]
  12. Dallere S, Rasà DM, Pavarino G, Schellino R, Vercelli A, Boido M. The exposome from neurodevelopment to neurodegeneration: A narrative review. Neurosci Biobehav Rev. 2025; 176: 106247. [CrossRef] [Google scholar]
  13. Gu Q, Liu J, Zhang X, Huang A, Yu X, Wu K, et al. Association between heavy metals exposure and risk of attention deficit hyperactivity disorder (ADHD) in children: A systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2025; 34: 921-941. [CrossRef] [Google scholar]
  14. Ehsanifar M, Esmaeili A. Neurotoxicity following exposure to chlorpyrifos. OBM Neurobiol. 2025; 9: 284. [CrossRef] [Google scholar]
  15. Hou C, Ren W, Wang B, Fu XA, Liu Q, Li J, et al. A bibliometric and knowledge-map analysis of the glymphatic system from 2012 to 2022. Front Mol Neurosci. 2023; 16: 1148179. [CrossRef] [Google scholar]
  16. Al Masri M, Corell A, Michaëlsson I, Jakola AS, Skoglund T. The glymphatic system for neurosurgeons: A scoping review. Neurosurg Rev. 2024; 47: 61. [CrossRef] [Google scholar]
  17. Hablitz LM, Nedergaard M. The glymphatic system. Curr Biol. 2021; 31: R1371-R1375. [CrossRef] [Google scholar]
  18. Xiong Y, Yu Q, Zhi H, Peng H, Xie M, Li R, et al. Advances in the study of the glymphatic system and aging. CNS Neurosci Ther. 2024; 30: e14803. [CrossRef] [Google scholar]
  19. Zou K, Deng Q, Zhang H, Huang C. Glymphatic system: A gateway for neuroinflammation. Neural Regen Res. 2024; 19: 2661-2672. [CrossRef] [Google scholar]
  20. Barlattani T, Grandinetti P, Cintio AD, Montemagno A, Testa R, D’Amelio C, et al. Glymphatic system and psychiatric disorders: A rapid comprehensive scoping review. Curr Neuropharmacol. 2024; 22: 2016-2033. [CrossRef] [Google scholar]
  21. Fang Y, Peng J, Chu T, Gao F, Xiong F, Tu Y. Glymphatic system dysfunction in adult ADHD: Relationship to cognitive performance. J Affect Disord. 2025; 379: 150-158. [CrossRef] [Google scholar]
  22. Sotgiu S, Cavassa V, Puci MV, Sotgiu MA, Turilli D, Jacono AL et al. Enlarged perivascular spaces under the dorso-lateral prefrontal cortex and severity of autism. Sci Rep. 2025; 15: 8142. [CrossRef] [Google scholar]
  23. Wang M, He K, Zhang L, Xu D, Li X, Wang L, et al. Assessment of glymphatic function and white matter integrity in children with autism using multi-parametric MRI and machine learning. Eur Radiol. 2025; 35: 1623-1636. [CrossRef] [Google scholar]
  24. Garic D, McKinstry RC, Rutsohn J, Slomowitz R, Wolff J, MacIntyre LC, et al. Enlarged perivascular spaces in infancy and autism diagnosis, cerebrospinal fluid volume, and later sleep problems. JAMA Netw Open. 2023; 6: e2348341. [CrossRef] [Google scholar]
  25. Chong PL, Garic D, Shen MD, Lundgaard I, Schwichtenberg AJ. Sleep, cerebrospinal fluid, and the glymphatic system: A systematic review. Sleep Med Rev. 2022; 61: 101572. [CrossRef] [Google scholar]
  26. Sotgiu MA, Lo Jacono A, Barisano G, Saderi L, Cavassa V, Montella A, et al. Brain perivascular spaces and autism: Clinical and pathogenic implications from an innovative volumetric MRI study. Front Neurosci. 2023; 17: 1205489. [CrossRef] [Google scholar]
  27. Li X, Ruan C, Zibrila AI, Musa M, Wu Y, Zhang Z, et al. Children with autism spectrum disorder present glymphatic system dysfunction evidenced by diffusion tensor imaging along the perivascular space. Medicine. 2022; 101: e32061. [CrossRef] [Google scholar]
  28. Tian P, Xue Y, Zhu X, Liu Z, Bian B, Jia F, et al. Abnormal glymphatic system function in children with autism spectrum disorder: A diffusion kurtosis imaging study. Eur J Pediatr. 2025; 184: 411. [CrossRef] [Google scholar]
  29. Chen Y, Wang M, Su S, Dai Y, Zou M, Lin L, et al. Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder. Eur Radiol. 2024; 34: 1444-1452. [CrossRef] [Google scholar]
  30. Tu Y, Fang Y, Li G, Xiong F, Gao F. Glymphatic system dysfunction underlying schizophrenia is associated with cognitive impairment. Schizophr Bull. 2024; 50: 1223-1231. [CrossRef] [Google scholar]
  31. Wu H, Liu B, Liu WV, Wen Z, Yang W, Yang H, et al. Glymphatic system dysfunction correlated with gut dysbiosis and cognitive impairment in schizophrenia. Schizophrenia. 2025; 11: 113. [CrossRef] [Google scholar]
  32. Abdolizadeh A, Torres-Carmona E, Kambari Y, Amaev A, Song J, Ueno F, et al. Evaluation of the glymphatic system in schizophrenia spectrum disorder using proton magnetic resonance spectroscopy measurement of brain macromolecule and diffusion tensor image analysis along the perivascular space index. Schizophr Bull. 2024; 50: 1396-1410. [CrossRef] [Google scholar]
  33. Sokan-Adeaga AA, Sokan-Adeaga MA, Sokan-Adeaga ED, Oparaji AN, Edris H, Tella EO, et al. Environmental toxicants and health adversities: A review on interventions of phytochemicals. J Public Health Res. 2023; 12: 22799036231181226. [CrossRef] [Google scholar]
  34. Rentschler J, Leonova N. Global air pollution exposure and poverty. Nat Commun. 2023; 14: 4432. [CrossRef] [Google scholar]
  35. Silva KC, Oliveira GE, Amarante MK, Panis C. Evidence concerning parental exposure to pesticides and the occurrence of leukemia in offspring: A systematic review. Front Pediatr. 2025; 13: 1560678. [CrossRef] [Google scholar]
  36. Xie PP, Zong ZQ, Qiao JC, Li ZY, Hu CY. Exposure to pesticides and risk of colorectal cancer: A systematic review and meta-analysis. Environ Pollut. 2024; 345: 123530. [CrossRef] [Google scholar]
  37. Ehsanifar M, Esmaeili A, Ahmadi O. Oxidative stress and endocrine disruption following exposure to chlorpyrifos. Casp J Health Res. 2025; 10: 93-100. [Google scholar]
  38. Gerken J, Vincent GT, Zapata D, Barron IG, Zapata I. Comprehensive assessment of pesticide use patterns and increased cancer risk. Front Cancer Control Soc. 2024; 2: 1368086. [CrossRef] [Google scholar]
  39. Ehsanifar M, Yavari Z. Neurotoxicity following exposure to micro and nanoplastics. OBM Neurobiol. 2025; 9: 277. [CrossRef] [Google scholar]
  40. Zhao B, Rehati P, Yang Z, Cai Z, Guo C, Li Y. The potential toxicity of microplastics on human health. Sci Total Environ. 2024; 912: 168946. [CrossRef] [Google scholar]
  41. Ding Y, Fang W, Wang T. Microplastic pollution in Chinese bays: Sampling method comparisons, key drivers, and economic influence. J Hazard Mater. 2025; 496: 139546. [CrossRef] [Google scholar]
  42. Islam MT, Antu UB, Hossain MS, Paul JR, Hasan T, Singha P, et al. Microplastic toxicity in fish: A potential review on sources, impacts, and solution. Aquat Toxicol. 2025; 287: 107498. [CrossRef] [Google scholar]
  43. Giechaskiel B, Grigoratos T, Mathissen M, Quik J, Tromp P, Gustafsson M, et al. Contribution of road vehicle tyre wear to microplastics and ambient air pollution. Sustainability. 2024; 16: 522. [CrossRef] [Google scholar]
  44. Luo D, Chu X, Wu Y, Wang Z, Liao Z, Ji X, et al. Micro-and nano-plastics in the atmosphere: A review of occurrence, properties and human health risks. J Hazard Mater. 2024; 465: 133412. [CrossRef] [Google scholar]
  45. Tunali M, Nowack B. Towards including soil ecotoxicity of microplastics and tire wear particles into life cycle assessment. Ecotoxicol Environ Saf. 2025; 303: 118856. [CrossRef] [Google scholar]
  46. Di Bella CE, D’Agostino C, Peregrina DV, Gigliobianco MR. Advanced characterization of sustainable exfoliating particles from food waste for facial scrub formulations and their in vivo evaluation. Sustain Chem Pharm. 2025; 44: 101953. [CrossRef] [Google scholar]
  47. Ranjan VP, Joseph A, Srivastava S, Sharma HB, Biswas B, Goel S, et al. From cosmetics to contamination: Microplastics in personal care products as vectors for chromium in aquatic environments. Waste Manage Bull. 2024; 2: 229-240. [CrossRef] [Google scholar]
  48. Luo Q, Tan H, Ye M, Jho EH, Wang P, Iqbal B, et al. Microplastics as an emerging threat to human health: An overview of potential health impacts. J Environ Manage. 2025; 387: 125915. [CrossRef] [Google scholar]
  49. Tian L, Zhang Y, Chen J, Liu X, Nie H, Li K, et al. Effects of nanoplastic exposure during pregnancy and lactation on neurodevelopment of rat offspring. J Hazard Mater. 2024; 474: 134800. [CrossRef] [Google scholar]
  50. Chen J, Song P, Li C, Liu H, Zhang L, Zhou Y, et al. Endocrine disrupting chemicals exposure and health: An umbrella review. Ecotoxicol Environ Saf. 2025; 302: 118574. [CrossRef] [Google scholar]
  51. Rodprasert W, Toppari J, Virtanen HE. Environmental toxicants and male fertility. Best Pract Res Clin Obstet Gynaecol. 2023; 86: 102298. [CrossRef] [Google scholar]
  52. Ehsanifar M, Gholami A, Esmaeili A. Mental health disorders following exposure to endocrine disruptor chemicals. OBM Neurobiol. 2025; 9: 285. [CrossRef] [Google scholar]
  53. Tzouma Z, Dourou P, Diamanti A, Harizopoulou V, Papalexis P, Karampas G, et al. Associations between endocrine-disrupting chemical exposure and fertility outcomes: A decade of human epidemiological evidence. Life. 2025; 15: 993. [CrossRef] [Google scholar]
  54. Naidu R, Espana VA, Liu Y, Jit J. Emerging contaminants in the environment: Risk-based analysis for better management. Chemosphere. 2016; 154: 350-357. [CrossRef] [Google scholar]
  55. Gavrilescu M, Demnerová K, Aamand J, Agathos S, Fava F. Emerging pollutants in the environment: Present and future challenges in biomonitoring, ecological risks and bioremediation. New Biotechnol. 2015; 32: 147-156. [CrossRef] [Google scholar]
  56. Li Y, Li Y, Zhang S, Gao T, Gao Z, Lai CW, et al. Global distribution, ecotoxicity, and treatment technologies of emerging contaminants in aquatic environments: A recent five-year review. Toxics. 2025; 13: 616. [CrossRef] [Google scholar]
  57. Puri M, Gandhi K, Suresh Kumar M. A global overview of endocrine disrupting chemicals in the environment: Occurrence, effects, and treatment methods. Int J Environ Sci Technol. 2023; 20: 12875-12902. [CrossRef] [Google scholar]
  58. Mišľanová C, Valachovičová M. Health impacts of per-and polyfluoroalkyl substances (PFASs): A comprehensive review. Life. 2025; 15: 573. [CrossRef] [Google scholar]
  59. Liu D, Yan S, Liu Y, Chen Q, Ren S. Association of prenatal exposure to perfluorinated and polyfluoroalkyl substances with childhood neurodevelopment: A systematic review and meta-analysis. Ecotoxicol Environ Saf. 2024; 271: 115939. [CrossRef] [Google scholar]
  60. Marques-da-Silva D, Videira PA, Lagoa R. Registered human trials addressing environmental and occupational toxicant exposures: Scoping review of immunological markers and protective strategies. Environ Toxicol Pharmacol. 2022; 93: 103886. [CrossRef] [Google scholar]
  61. Weatherly LM, Shane HL, Jackson LG, Lukomska E, Baur R, Cooper MP, et al. Systemic and immunotoxicity induced by topical application of perfluorohexane sulfonic acid (PFHxS) in a murine model. Food Chem Toxicol. 2024; 186: 114578. [CrossRef] [Google scholar]
  62. Li X, Zhang X, Zhang Z, Han L, Gong D, Li J, et al. Air pollution exposure and immunological and systemic inflammatory alterations among schoolchildren in China. Sci Total Environ. 2019; 657: 1304-1310. [CrossRef] [Google scholar]
  63. Massrali A, Adhya D, Srivastava DP, Baron-Cohen S, Kotter MR. Virus-induced maternal immune activation as an environmental factor in the etiology of autism and schizophrenia. Front Neurosci. 2022; 16: 834058. [CrossRef] [Google scholar]
  64. Han VX, Patel S, Jones HF, Dale RC. Maternal immune activation and neuroinflammation in human neurodevelopmental disorders. Nat Rev Neurol. 2021; 17: 564-579. [CrossRef] [Google scholar]
  65. Ehsanifar M, Rajati R, Gholami A, Reiss JP. Mold and mycotoxin exposure and brain disorders. J Integr Neurosci. 2023; 22: 137. [CrossRef] [Google scholar]
  66. Ehsanifar M, Montazeri Z, Taheri MA, Rafati M, Behjati M, Karimian M. Hippocampal inflammation and oxidative stress following exposure to diesel exhaust nanoparticles in male and female mice. Neurochem Int. 2021; 145: 104989. [CrossRef] [Google scholar]
  67. Ehsanifar M, Jafari AJ, Montazeri Z, Kalantari RR, Gholami M, Ashtarinezhad A. Learning and memory disorders related to hippocampal inflammation following exposure to air pollution. J Environ Health Sci Eng. 2021; 19: 261-272. [CrossRef] [Google scholar]
  68. Ehsanifar M, Jafari AJ, Nikzad H, Zavareh MS, Atlasi MA, Mohammadi H, et al. Prenatal exposure to diesel exhaust particles causes anxiety, spatial memory disorders with alters expression of hippocampal pro-inflammatory cytokines and NMDA receptor subunits in adult male mice offspring. Ecotoxicol Environ Saf. 2019; 176: 34-41. [CrossRef] [Google scholar]
  69. Pan R, Yi X, Xu Y, Song J, Yi W, Liu J, et al. Association between indoor PM2.5 components and accelerated biological aging in schizophrenia patients: Evidence from multi-omics mechanisms. J Hazard Mater. 2024; 480: 136162. [CrossRef] [Google scholar]
  70. Gao X, Zheng X, Wang X, Li Z, Yang L. Environmental pollutant exposure and adverse neurodevelopmental outcomes: An umbrella review and evidence grading of meta-analyses. J Hazard Mater. 2025; 491: 137832. [CrossRef] [Google scholar]
  71. Winstone JK, Pathak KV, Winslow W, Piras IS, White J, Sharma R, et al. Glyphosate infiltrates the brain and increases pro-inflammatory cytokine TNFα: Implications for neurodegenerative disorders. J Neuroinflammation. 2022; 19: 193. [CrossRef] [Google scholar]
  72. Paradis M, Kucharowski N, Edwards Faret G, Maya Palacios SJ, Meyer C, Stümpges B, et al. The ER protein Creld regulates ER-mitochondria contact dynamics and respiratory complex 1 activity. Sci Adv. 2022; 8: eabo0155. [CrossRef] [Google scholar]
  73. Zhao X, Cao R, Tian X, Liu P, Liu D, Yu X, et al. OAB-14 attenuated glymphatic system disorder, neuroinflammation and Dyskinesia in Parkinson’s disease model mice induced by rotenone. Neurochem Res. 2025; 50: 142. [CrossRef] [Google scholar]
  74. Sun M, Zhang M, Di F, Bai W, Sun J, Zhang M, et al. Polystyrene nanoplastics induced learning and memory impairments in mice by damaging the glymphatic system. Ecotoxicol Environ Saf. 2024; 284: 116874. [CrossRef] [Google scholar]
  75. Gong W, Zhai Q, Wang Y, Shen A, Huang Y, Shi K, et al. Glymphatic function and choroid plexus volume is associated with systemic inflammation and oxidative stress in major depressive disorder. Brain Behav Immun. 2025; 128: 266-275. [CrossRef] [Google scholar]
  76. Liang S, Liu H, Wang X, Lin H, Zheng L, Zhang Y, et al. Aerobic exercise improves clearance of amyloid-β via the glymphatic system in a mouse model of Alzheimer’s Disease. Brain Res Bull. 2025; 222: 111263. [CrossRef] [Google scholar]
  77. Li M, Xu J, Li L, Zhang L, Zuo Z, Feng Y, et al. Voluntary wheel exercise improves glymphatic clearance and ameliorates colitis-associated cognitive impairment in aged mice by inhibiting TRPV4-induced astrocytic calcium activity. Exp Neurol. 2024; 376: 114770. [CrossRef] [Google scholar]
  78. Zhang SS, Meng FG, Rong YY, Zhang YW, Liu HQ. Dexmedetomidine and the glymphatic system: A new perspective in managing postoperative cognitive dysfunction. Front Pharmacol. 2025; 16: 1648308. [CrossRef] [Google scholar]
  79. Persson ND, Lohela TJ, Mortensen KN, Rosenholm M, Li Q, Weikop P, et al. Anesthesia blunts carbon dioxide effects on glymphatic cerebrospinal fluid dynamics in mechanically ventilated rats. Anesthesiology. 2024; 141: 338-352. [CrossRef] [Google scholar]
  80. Liao J, Duan Y, Liu Y, Chen H, An Z, Chen Y, et al. Simvastatin alleviates glymphatic system damage via the VEGF-C/VEGFR3/PI3K-Akt pathway after experimental intracerebral hemorrhage. Brain Res Bull. 2024; 216: 111045. [CrossRef] [Google scholar]
  81. Chen Y, Guo H, Sun X, Wang S, Zhao M, Gong J, et al. Melatonin regulates glymphatic function to affect cognitive deficits, behavioral issues, and blood–brain barrier damage in mice after intracerebral hemorrhage: Potential links to circadian rhythms. CNS Neuroscie Ther. 2025; 31: e70289. [CrossRef] [Google scholar]
  82. Sripetchwandee J, Pipatpiboon N, Chattipakorn N, Chattipakorn S. Combined therapy of iron chelator and antioxidant completely restores brain dysfunction induced by iron toxicity. PLoS One. 2014; 9: e85115. [CrossRef] [Google scholar]
  83. Mahanta AK, Gothwal A, Chaulagain B, Muolokwu CE, Tagoe B, Lamsal B, et al. Emerging anti-inflammatory nanosystems targeted to the brain. Nanomedicine. 2025; 20: 2237-2255. [CrossRef] [Google scholar]
Journal Metrics
2024
CiteScore SJR SNIP
1.20.2050.249
Newsletter
Download PDF Download Citation
0 0
Newsletter  

TOP