We can't find the internet
Attempting to reconnect
Something went wrong!
Hang in there while we get back on track
Towards the development and applications of blood-brain barrier in vitro models for neurotoxicity assessment
Summary
Researchers reviewed the current state of in vitro blood-brain barrier models and their utility for evaluating the neurotoxic potential of environmental contaminants including micro- and nanoplastics. The review identifies validation challenges and argues for more human-relevant model systems to close gaps in regulatory neurotoxicity assessment.
To perform risk assessment of chemicals, drugs and particles, the regulatory OECD guidelines to determine neurotoxicity are based on animal testing. In addition to ethical concerns, inherent problems such as lack of translatability between animals and humans encouraged the development of new approach methodologies (NAMs) such as in silico and in vitro models. The development and validation of robust NAMs fit for regulatory needs are in line and support the current European policy of phasing out animal testing for which the European Commission will publish the roadmap in Q1/2026. The OECD has identified the role of the blood brain barrier as a gap in the developmental neurotoxicity (DNT) test batteries currently being developed. As part of the European Partnership Programme PARC with over 200 participating research institutions, we developed different set-ups for adult neurotoxicity (ANT) and DNT testing based either on human iPSC derived brain capillary endothelial-like cells (BCECs) or the immortalized cell line hCMEC/D3. The development of the BBB in vitro models, their applications and findings will be presented. A set of selected neurotoxins, a mixture of PFAS and various nanoplastics were tested and showcased the broad applicability of the models obtaining data in one test set-up about permeability, changes of the barrier properties, the communication of the BBB with various CNS cells and effects on CNS cells on functional and molecular levels (e.g. RNAseq, DNA- methylation). One out of several interesting findings was the relevance of medium pH indicator phenolred for the successful BCECs differentiation revealed during studies about endocrine disruptors. Acknowledgement: This work was carried out in the framework of the European Partnership for the Assessment of Risks from Chemical (PARC) and has received funding from the European Union’s Horizon Europe Research and Innovation Programme under Grant Agreement No 101057014, the project CHIASMA has received funding from the European Union’s Horizon Europe Research and Innovation Programme: Grant Agreement No. 101137613, the project InChildHealth has received funding from the European Union’s Horizon Europe Research and Innovation Programme: Grant Agreement No. 101056883. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Health and Digital Executive Agency (HaDEA). Neither the European Union nor the granting authority can be held responsible for them. We further gratefully acknowledge the financial support provided by the Austrian Science Fund FWF (project P 34137-B).
Sign in to start a discussion.
More Papers Like This
Towards the development and applications of blood-brain barrier in vitro models for neurotoxicity assessment
This review examined the development and applications of in vitro blood-brain barrier models for assessing neurotoxicity of chemicals, drugs, and particles including nanoplastics. The authors argue that human cell-derived BBB models are critical alternatives to animal testing for predicting neurological effects of emerging contaminants.
Mechanisms of micro- and nanoplastics on blood-brain barrier crossing and neurotoxicity: Current evidence and future perspectives
This review examines evidence that micro- and nanoplastics can cross the blood-brain barrier, the protective shield around the brain, through multiple pathways including disrupting the barrier's tight junctions and being transported inside cells. Once in the brain, these particles may cause damage through oxidative stress, inflammation, mitochondrial dysfunction, and disrupted iron metabolism, with effects worsened when plastics carry other pollutants like heavy metals.
Micro-nanoplastics in the central nervous system: Evidence, mechanisms and perspectives
This review examines evidence that micro- and nanoplastics can cross the blood-brain barrier and cause neurotoxicity through oxidative stress, neuroinflammation, and disruption of neurotransmitter signaling. While clinical studies have confirmed the presence of plastic particles in human brain tissue and cerebrospinal fluid, the authors note that methodological limitations and inconsistent quality controls currently prevent establishing a definitive causal link to neurological conditions.
A systematic review of the potential neurotoxicity of micro-and nanoplastics: the known and unknown
This critical review of 234 studies found that micro- and nanoplastics can reach the brain via olfactory translocation or by crossing the blood-brain barrier, where they may cause neuroinflammation, oxidative damage, and behavioral changes in animal models. The evidence raises significant concerns about potential neurotoxic effects of chronic microplastic exposure in humans, though major knowledge gaps remain.
Insights into the toxic effects of micro-nano-plastics on the human brain and their relationship with the onset of neurological diseases: A narrative review.
This review examined toxic effects of micro and nano-plastics (MNPs) on the human brain, linking MNP exposure to neuroinflammation, oxidative stress, disruption of the blood-brain barrier, and progression toward neurodegenerative diseases. The authors synthesized evidence from cell studies, animal models, and emerging human data.