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All Rights Reserved [Search All ] [ ] Input Search Term [ ] Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In full text icon Full Text contents icon Contents figure icon Figures / Tables multimedia icon Multimedia attach icon Supplemental Content references icon References related icon Related comments icon Comments Download PDF Comment Top of Article * Key Points * Abstract * Introduction * Methods * Results * Discussion * Conclusions * Article Information * References Figure 1. Microphotographs and Micro-Fourier Transform Infrared (mFTIR) Spectra of the Microplastics Found in the Olfactory Bulb Tissue View LargeDownload HQI indicates hit quality index. Figure 2. Microphotographs and Micro-Fourier Transform Infrared (mFTIR) Spectra of the Main Microplastics Found in the Digested Olfactory Bulb View LargeDownload HQI indicates hit quality index. Table 1. Demographic and Autopsy Findings of the Decedents View LargeDownload Table 2. Morphology and Polymeric Matrix of the Identified Particles and Fibers View LargeDownload Supplement 1. eFigure. Microphotographs and uFTIR Spectra of the Microplastics Found in the Digested Olfactory Bulb Supplement 2. Data Sharing Statement 1. Li Y, Tao L, Wang Q, Wang F, Li G, Song M. Potential health impact of microplastics: a review of environmental distribution, human exposure, and toxic effects. Environ Health. 2023;1 (4):249-257. doi:10.1021/envhealth.3c00052Google ScholarCrossref 2. Marfella R, Prattichizzo F, Sardu C, et al. Microplastics and nanoplastics in atheromas and cardiovascular events. N Engl J Med. 2024;390(10):900-910. doi:10.1056/NEJMoa2309822PubMedGoogle Scholar Crossref 3. Jenner LC, Rotchell JM, Bennett RT, Cowen M, Tentzeris V, Sadofsky LR. Detection of microplastics in human lung tissue using mFTIR spectroscopy. Sci Total Environ. 2022;831:154907. doi:10.1016 /j.scitotenv.2022.154907PubMedGoogle ScholarCrossref 4. Amato-Lourenco LF, Carvalho-Oliveira R, Junior GR, Dos Santos Galvao L, Ando RA, Mauad T. Presence of airborne microplastics in human lung tissue. J Hazard Mater. 2021;416:126124. doi:10.1016/ j.jhazmat.2021.126124PubMedGoogle ScholarCrossref 5. Zhu L, Kang Y, Ma M, et al. Tissue accumulation of microplastics and potential health risks in human. Sci Total Environ. 2024; 915:170004. doi:10.1016/j.scitotenv.2024.170004PubMedGoogle Scholar Crossref 6. Horvatits T, Tamminga M, Liu B, et al. Microplastics detected in cirrhotic liver tissue. EBioMedicine. 2022;82:104147. doi:10.1016/ j.ebiom.2022.104147PubMedGoogle ScholarCrossref 7. Halfar J, Cabanova K, Vavra K, et al. Microplastics and additives in patients with preterm birth: the first evidence of their presence in both human amniotic fluid and placenta. Chemosphere. 2023;343:140301. doi:10.1016/j.chemosphere.2023.140301PubMedGoogle ScholarCrossref 8. Ragusa A, Svelato A, Santacroce C, et al. Plasticenta: First evidence of microplastics in human placenta. Environ Int. 2021; 146:106274. doi:10.1016/j.envint.2020.106274PubMedGoogle Scholar Crossref 9. Montano L, Giorgini E, Notarstefano V, et al. Raman microspectroscopy evidence of microplastics in human semen. Sci Total Environ. 2023;901:165922. doi:10.1016/j.scitotenv.2023.165922 PubMedGoogle ScholarCrossref 10. Leslie HA, van Velzen MJM, Brandsma SH, Vethaak AD, Garcia-Vallejo JJ, Lamoree MH. Discovery and quantification of plastic particle pollution in human blood. Environ Int. 2022; 163:107199. doi:10.1016/j.envint.2022.107199PubMedGoogle Scholar Crossref 11. Kopatz V, Wen K, Kovacs T, et al. Micro- and nanoplastics breach the blood-brain barrier (BBB): biomolecular corona's role revealed. Nanomaterials (Basel). 2023;13(8):1404. doi:10.3390/nano13081404 PubMedGoogle ScholarCrossref 12. Jin H, Yang C, Jiang C, et al. Evaluation of neurotoxicity in BALB/c mice following chronic exposure to polystyrene microplastics. 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Amato-Lourenco LF, Dos Santos Galvao L, Wiebeck H, Carvalho-Oliveira R, Mauad T. Atmospheric microplastic fallout in outdoor and indoor environments in Sao Paulo megacity. Sci Total Environ. 2022;821:153450. doi:10.1016/j.scitotenv.2022.153450PubMed Google ScholarCrossref 22. Torres-Agullo A, Karanasiou A, Lacorte S. Nasal lavage technique reveals regular inhalation exposure of microplastics, not associated from face mask use. Environ Int. 2023;178:108129. doi:10.1016/ j.envint.2023.108129PubMedGoogle ScholarCrossref 23. Tuna A, Tas BM, Basaran Kankilic G, et al. Detection of microplastics in patients with allergic rhinitis. Eur Arch Otorhinolaryngol. 2023;280(12):5363-5367. doi:10.1007/ s00405-023-08105-7PubMedGoogle ScholarCrossref 24. Gao W, Deng XJ, Zhang J, Qi L, Zhao XQ, Zhang PY. Assessment of quality control measures in the monitoring of microplastic: a critical review. Environmental Pollutants and Bioavailability. 2023;35(1). doi:10.1080/26395940.2023.2203349Google ScholarCrossref 25. Gwinnett C, Miller RZ. Are we contaminating our samples? A preliminary study to investigate procedural contamination during field sampling and processing for microplastic and anthropogenic microparticles. Mar Pollut Bull. 2021;173(Pt B):113095. doi:10.1016 /j.marpolbul.2021.113095Google ScholarCrossref 26. Rochman CM,, Brookson C,, Bikker J,, et al. Rethinking microplastics as a diverse contaminant suite. Environ Toxicol Chem. 2019;38(4):703-711. doi:10.1002/etc.4371Google ScholarCrossref 27. Jackson M, Mantsch HH. The use and misuse of FTIR spectroscopy in the determination of protein structure. Crit Rev Biochem Mol Biol. 1995;30(2):95-120. doi:10.3109/10409239509085140PubMedGoogle Scholar Crossref 28. De Frond H, Rubinovitz R, Rochman CM. mATR-FTIR spectral libraries of plastic particles (FLOPP and FLOPP-e) for the analysis of microplastics. Anal Chem. Published online November 23, 2021. doi:10.1021/acs.analchem.1c02549PubMedGoogle ScholarCrossref 29. Primpke S, Cross RK, Mintenig SM, et al. Toward the systematic identification of microplastics in the environment: evaluation of a new independent software tool (siMPle) for spectroscopic analysis. Appl Spectrosc. 2020;74(9):1127-1138. doi:10.1177/0003702820917760 PubMedGoogle ScholarCrossref 30. Weisser J, Pohl T, Heinzinger M, Ivleva NP, Hofmann T, Glas K. The Identification of Microplastics Based on Vibrational Spectroscopy Data--A Critical Review of Data Analysis Routines. TrAC. Trends Analyt Chem. 2022;148:116535. doi:10.1016/j.trac.2022.116535 Google ScholarCrossref 31. Morgado V, Palma C, Bettencourt da Silva RJN. Microplastics identification by infrared spectroscopy - Evaluation of identification criteria and uncertainty by the Bootstrap method. Talanta. 2021;224:121814. doi:10.1016/j.talanta.2020.121814PubMed Google Scholar 32. Abolmaali N, Gudziol V, Hummel T. Pathology of the olfactory nerve. Neuroimaging Clin N Am. 2008;18(2):233-42. doi:10.1016/ j.nic.2007.10.002Google Scholar 33. Spera I, Cousin N, Ries M, et al. Open pathways for cerebrospinal fluid outflow at the cribriform plate along the olfactory nerves. EBioMedicine. 2023;91:104558. doi:10.1016/ j.ebiom.2023.104558PubMedGoogle Scholar 34. Krmpotic-Nemanic J, Padovan I, Vinter I, Jalsovec D. Development of the cribriform plate and of the lamina mediana. Ann Anat. 1998; 180(6):555-559. doi:10.1016/S0940-9602(98)80065-4PubMedGoogle Scholar 35. Kalmey JK, Thewissen JG, Dluzen DE. Age-related size reduction of foramina in the cribriform plate. Anat Rec. 1998;251(3):326-329. doi:10.1002/(SICI)1097-0185(199807)251:3<326::AID-AR7>3.0.CO;2-T PubMedGoogle Scholar 36. Kincaid AE, Ayers JI, Bartz JC. Specificity, size, and frequency of spaces that characterize the mechanism of bulk transepithelial transport of prions in the nasal cavities of hamsters and mice. J Virol. 2016;90(18):8293-8301. doi:10.1128/JVI.01103-16PubMedGoogle Scholar 37. Akhbarizadeh R, Dobaradaran S, Amouei Torkmahalleh M, Saeedi R, Aibaghi R, Faraji Ghasemi F. Suspended fine particulate matter (PM [2.5]), microplastics (MPs), and polycyclic aromatic hydrocarbons (PAHs) in air: their possible relationships and health implications. Environ Res. 2021;192:110339. doi:10.1016/j.envres.2020.110339PubMed Google Scholar 38. Braithwaite I, Zhang S, Kirkbride JB, Osborn DPJ, Hayes JF. Air pollution (particulate matter) exposure and associations with depression, anxiety, bipolar, psychosis and suicide risk: a systematic review and meta-analysis. Environ Health Perspect. 2019; 127(12):126002. doi:10.1289/EHP4595PubMedGoogle Scholar 39. Kioumourtzoglou MA, Schwartz JD, Weisskopf MG, et al. Long-term PM2.5 exposure and neurological hospital admissions in the northeastern United States. Environ Health Perspect. 2016;124 (1):23-29. doi:10.1289/ehp.1408973PubMedGoogle Scholar 40. Fullard ME, Morley JF, Duda JE. Olfactory dysfunction as an early biomarker in Parkinson's disease. Neurosci Bull. 2017;33 (5):515-525. doi:10.1007/s12264-017-0170-xPubMedGoogle Scholar 41. Liu XQ, Huang J, Song C, Zhang TL, Liu YP, Yu L. Neurodevelopmental toxicity induced by PM2.5 exposure and its possible role in neurodegenerative and mental disorders. Hum Exp Toxicol. Published online August 3, 2023. doi:10.1177/ 09603271231191436PubMedGoogle Scholar 42. Prust M, Meijer J, Westerink RHS. The plastic brain: neurotoxicity of micro- and nanoplastics. Part Fibre Toxicol. 2020; 17(1):24. doi:10.1186/s12989-020-00358-yPubMedGoogle Scholar 43. Zhu J, Zhang X, Liao K, Wu P, Jin H. Microplastics in dust from different indoor environments. Sci Total Environ. 2022;833:155256. doi:10.1016/j.scitotenv.2022.155256PubMedGoogle Scholar 44. Jeong SH, Jang JH, Lee YB. Drug delivery to the brain via the nasal route of administration: exploration of key targets and major consideration factors. J Pharm Investig. 2023;53(1):119-152. doi: 10.1007/s40005-022-00589-5PubMedGoogle Scholar 45. Tas BM, Tuna A, Basaran Kankilic G, et al. Role of microplastics in chronic rhinosinusitis without nasal polyps. Laryngoscope. 2024; 134(3):1077-1080. doi:10.1002/lary.30926PubMedGoogle Scholar 46. Kempen JH. Appropriate use and reporting of uncontrolled case series in the medical literature. Am J Ophthalmol. 2011;151 (1):7-10.e1. doi:10.1016/j.ajo.2010.08.047PubMedGoogle Scholar See More About Environmental Health Neurology Pathology and Laboratory Medicine Toxicology Medical Education and Training --------------------------------------------------------------------- Sign Up for Emails Based on Your Interests Select Your Interests Customize your JAMA Network experience by selecting one or more topics from the list below. * Academic Medicine * Acid Base, Electrolytes, Fluids * Allergy and Clinical Immunology * American Indian or Alaska Natives * Anesthesiology * Anticoagulation * Art and Images in Psychiatry * Artificial Intelligence * Assisted Reproduction * Bleeding and Transfusion * Cardiology * Caring for the Critically Ill Patient * Challenges in Clinical Electrocardiography * Climate and Health * Climate Change * Clinical Challenge * Clinical Decision Support * Clinical Implications of Basic Neuroscience * Clinical Pharmacy and Pharmacology * Complementary and Alternative Medicine * Consensus Statements * Coronavirus (COVID-19) * Critical Care Medicine * Cultural Competency * Dental Medicine * Dermatology * Diabetes and Endocrinology * Diagnostic Test Interpretation * Drug Development * Electronic Health Records * Emergency Medicine * End of Life, Hospice, Palliative Care * Environmental Health * Equity, Diversity, and Inclusion * Ethics * Facial Plastic Surgery * Gastroenterology and Hepatology * Genetics and Genomics * Genomics and Precision Health * Geriatrics * Global Health * Guide to Statistics and Methods * Guidelines * Hair Disorders * Health Care Delivery Models * Health Care Economics, Insurance, Payment * Health Care Quality * Health Care Reform * Health Care Safety * Health Care Workforce * Health Disparities * Health Inequities * Health Policy * Health Systems Science * Hematology * History of Medicine * Humanities * Hypertension * Images in Neurology * Implementation Science * Infectious Diseases * Innovations in Health Care Delivery * JAMA Infographic * Law and Medicine * Leading Change * Less is More * LGBTQIA Medicine * Lifestyle Behaviors * Medical Coding * Medical Devices and Equipment * Medical Education * Medical Education and Training * Medical Journals and Publishing * Melanoma * Mobile Health and Telemedicine * Narrative Medicine * Nephrology * Neurology * Neuroscience and Psychiatry * Notable Notes * Nursing * Nutrition * Nutrition, Obesity, Exercise * Obesity * Obstetrics and Gynecology * Occupational Health * Oncology * Ophthalmology * Orthopedics * Otolaryngology * Pain Medicine * Palliative Care * Pathology and Laboratory Medicine * Patient Care * Patient Information * Pediatrics * Performance Improvement * Performance Measures * Perioperative Care and Consultation * Pharmacoeconomics * Pharmacoepidemiology * Pharmacogenetics * Pharmacy and Clinical Pharmacology * Physical Medicine and Rehabilitation * Physical Therapy * Physician Leadership * Poetry * Population Health * Primary Care * Professional Well-being * Professionalism * Psychiatry and Behavioral Health * Public Health * Pulmonary Medicine * Radiology * Regulatory Agencies * Reproductive Health * Research, Methods, Statistics * Resuscitation * Rheumatology * Risk Management * Scientific Discovery and the Future of Medicine * Shared Decision Making and Communication * Sleep Medicine * Sports Medicine * Stem Cell Transplantation * Substance Use and Addiction Medicine * Surgery * Surgical Innovation * Surgical Pearls * Teachable Moment * Technology and Finance * The Art of JAMA * The Arts and Medicine * The Rational Clinical Examination * Tobacco and e-Cigarettes * Toxicology * Translational Medicine * Trauma and Injury * Treatment Adherence * Ultrasonography * Urology * Users' Guide to the Medical Literature * Vaccination * Venous Thromboembolism * Veterans Health * Violence * Women's Health * Workflow and Process * Wound Care, Infection, Healing Get the latest research based on your areas of interest. [ ] Weekly Email [ ] Monthly Email Save Preferences Privacy Policy | Terms of Use Others Also Liked Comment 2 Comments for this article EXPAND ALL September 17, 2024 Surgical masks, friend or foe? Steven Reid, MD | Doctor Lifeline, Incorporated It would be very interesting to compare the olfactory bulb micro plastics burden between those who frequently utilize face masks, such as surgical teams, and those who have had little exposure to such masks. The masks themselves are largely made of synthetic fibers and could therefore be a source for increased micro plastics exposure. On the other hand, they could potentially filter out environmental exposure to micro plastics. Such data may have public health implications. CONFLICT OF INTEREST: None Reported September 17, 2024 Could health risks from microplastics and nanoplastics exposure vary with specific environmental factors or the local air quality? Giovanni Ghirga, Pediatrician | Italian Branch of the International Society of Doctors for the Environment, Bern, Switzerland Dear Editor Food and water are thought to be the major sources of microplastics and nanoplastics (MNPs) exposure, with more than 100,000 particles in each liter of bottled water, the majority of which are nanoplastics (1,2). Furthermore, we are exposed to MNPs in the atmosphere through the air we inhale. In a 2021 study, a team of researchers estimated that people in five Chinese megacities inhale 1-2 million MNPs annually; thus, air exposure poses a significant concern because after inhaling, MNPs can rapidly reach every organ and tissue (3). MNPs take various forms, are primary or secondary, and can have wildly different sizes, shapes, and chemical formulations--all of which can impact their toxicity. Plastic polymers, typically considered to be chemically inactive, can impact biological processes through their physical presence alone. MNPs may contain or come in contact with biologically active chemicals. Once released into the environment, MNPs can attract and accumulate a variety of other contaminants. Due to their physical properties, such as hydrophobicity and large surface area in relation to their volume, MNPs can act as sponges for toxic metals, polycyclic aromatic hydrocarbons, and other hazardous chemicals. This absorption can lead to the bioaccumulation of these contaminants in organisms that ingest, inhale, or come into contact with MNPs, potentially detrimental to human well-being and ecosystem health. Depending on the location and source of the MNPs, the composition and toxicity of these absorbed chemicals can vary significantly. For example, in areas with high levels of industrial pollution, MNPs may become coated with a range of toxic chemicals, including heavy metals, pesticides, polycyclic aromatic hydrocarbons, and other industrial byproducts. In contrast, the absorbed chemicals may be less harmful or minimal in quantity in more pristine environments. This variation in composition and toxicity of absorbed chemicals onto the surfaces of MNPs means that the health risk from exposure could significantly differ from one area to another. While the health hazards of ingesting or inhaling MNPs are still being investigated, the presence of hazardous chemicals on their surfaces is a well-established concern (4). Finally, this hypothesis could suggest the potential lower toxicity of the vast amount of MNPs formed in commonly used water bottles compared to those inhaled by residents in areas with low air quality. 1. Nicole W. An Ill Wind? Growing Recognition of Airborne Nano- and Microplastic Exposures. Environ Health Perspect. 2023 Apr;131 (4):42001. doi: 10.1289/EHP12662. Epub 2023 Apr 28. PMID: 37116008; PMCID: PMC10146709. 2. Qian N, Gao X, Lang X, Deng H, Bratu TM, Chen Q, Stapleton P, Yan B, Min W. Rapid single-particle chemical imaging of nanoplastics by SRS microscopy. Proc Natl Acad Sci U S A. 2024 Jan 16;121 (3):e2300582121. doi: 10.1073/pnas.2300582121. Epub 2024 Jan 8. PMID: 38190543; PMCID: PMC10801917. 3. Zhu X, Huang W, Fang M, Liao Z, Wang Y, Xu L, et al. 2021. Airborne microplastic concentrations in five megacities of Northern and southeast China. Environ Sci Technol 55(19):12871-12881, PMID: 34559513, https://doi.org/10.1021/acs.est.1c03618. 4. Ghirga G, Ghirga P, Orchi C. Microplastics and Nanoplastics in Atheromas. N Engl J Med. 2024;390(18):1726-1727. doi:10.1056/ NEJMc2404154 CONFLICT OF INTEREST: None Reported READ MORE This Issue Views 12,008 Citations 0 Comments 2 View Metrics * Download PDF * X Facebook More LinkedIn * Cite This Citation Amato-Lourenco LF, Dantas KC, Junior GR, et al. Microplastics in the Olfactory Bulb of the Human Brain. JAMA Netw Open. 2024;7 (9):e2440018. doi:10.1001/jamanetworkopen.2024.40018 Manage citations: Ris (Zotero) EndNote BibTex Medlars ProCite RefWorks Reference Manager Mendeley (c) 2024 * Permissions Original Investigation Environmental Health September 16, 2024 Microplastics in the Olfactory Bulb of the Human Brain Luis Fernando Amato-Lourenco, PhD^1,2; Katia Cristina Dantas, PhD^2; Gabriel Ribeiro Junior, PhD^2; et al Vitor Ribeiro Paes, MD^2; Romulo Augusto Ando, PhD^4; Raul de Oliveira Freitas, PhD^3; Ohanna Maria Menezes M. da Costa, PhD^3; Renata S. Rabelo, PhD^3; Kelly Cristina Soares Bispo^2; Regiani Carvalho-Oliveira, PhD^2; Thais Mauad, MD, PhD^2 Author Affiliations Article Information * ^1Institute of Biology, Freie Universitat Berlin, Berlin, Germany * ^2Department of Pathology, Sao Paulo Medical School, University of Sao Paulo, Sao Paulo, Brazil * ^3Brazilian Synchrotron Light Laboratory (LNLS), Brazilian Center for Research in Energy and Materials (CNPEM), Sao Paulo, Brazil * ^4Department of Fundamental Chemistry, Institute of Chemistry, University of Sao Paulo (IQUSP), Sao Paulo, Brazil JAMA Netw Open. 2024;7(9):e2440018. doi:10.1001/ jamanetworkopen.2024.40018 visual abstract icon Visual Abstract editorial comment icon Editorial Comment related articles icon Related Articles author interview icon Interviews multimedia icon Multimedia audio icon Listen to this article Key Points Question Can microplastics reach the olfactory bulb in the human brain? Findings This case series analyzed the olfactory bulbs of 15 deceased individuals via micro-Fourier transform infrared spectroscopy and detected the presence of microplastics in the olfactory bulbs of 8 individuals. The predominant shapes were particles and fibers, with polypropylene being the most common polymer. Meaning The presence of microplastics in the human olfactory bulb suggests the olfactory pathway as a potential entry route for microplastics into the brain, highlighting the need for further research on their neurotoxic effects and implications for human health. Abstract Importance Microplastic (MP) pollution is an emerging environmental and health concern. While MPs have been detected in various human tissues, their presence in the human brain has not been documented, raising important questions about potential neurotoxic effects and the mechanisms by which MPs might reach brain tissues. Objective To determine the presence of MPs in the human olfactory bulb and to analyze their characteristics such as size, morphology, color, and polymeric composition. Design, Setting, and Participants This case series study used a cross-sectional design involving the analysis of olfactory bulb tissues obtained from deceased individuals during routine coroner autopsies. The sampling procedures were conducted at Sao Paulo City Death Verification Service, with laboratory analysis carried out at the Brazilian Synchrotron Light Laboratory (LNLS). Participants included 15 adult individuals who had been residents of Sao Paulo for more than 5 years and underwent coroner autopsies. Exclusion criteria included previous neurosurgical interventions. Data analysis was performed in April 2024. Exposure The primary exposure assessed was the presence of MPs in the olfactory bulb, analyzed through direct tissue examination and digested tissue filtration followed by micro-Fourier transform infrared spectroscopy. Main Outcomes and Measures The main outcomes were the identification and characterization of MPs within the olfactory bulb, including their size, morphology, color, and polymeric composition. Results The median age of the 15 deceased individuals was 69.5 years, ranging from 33 to 100 years, with 12 males and 3 females. MPs were detected in the olfactory bulbs of 8 out of 15 individuals. A total of 16 synthetic polymer particles and fibers were identified, with 75% being particles and 25% being fibers. The most common polymer detected was polypropylene (43.8%). Sizes of MPs ranged from 5.5 mm to 26.4 mm for particles, and the mean fiber length was 21.4 mm. Polymeric materials were absent in procedural blank and negative control filters, indicating minimal contamination risk. Conclusions and Relevance This case series provides evidence of MPs found in the human olfactory bulb, suggesting a potential pathway for the translocation of MPs to the brain. The findings underscore the need for further research on the health implications of MP exposure, particularly concerning neurotoxicity and the potential for MPs to bypass the blood-brain barrier. Introduction The ubiquity of microplastic (MP) pollution has become a pervasive environmental concern,^1 raising questions about its occurrence within the human body and its harmful effects.^2 While MPs have been detected in various organs of the human body, such as the lungs,^3^,4 large and small intestines,^5 liver,^6 placenta,^7^,8 semen,^9 and bloodstream,^10 to our knowledge, there have been no published studies to date reporting their presence in the human brain. The presence of the blood-brain barrier (BBB) is likely an important limiting factor for the access of MPs to the human brain via hematogenous translocation. Despite this, some animal studies have shown that MPs can impair the BBB and reach the brain via oral ingestion, leading to neurotoxic effects.^11^-13 Another potential entry site for micro- and nanoplastics (MNPs) in the human brain is the olfactory pathway.^14 This pathway involves olfactory neurons in the nasal that transmit information about odors to the central olfactory system of the brain. Olfactory axons pass through the cribriform plate (CP) of the ethmoid bone and reach the olfactory bulbs (OB), which are connected to the limbic system of the brain. There are different levels of evidence suggesting that the olfactory pathway might allow the translocation of exogenous particles to the brain. Environmental black carbon particles have been detected in various human brain regions, with one of the highest concentrations found in the OB, measuring 420.8 particles/mm^3.^15 Rarely, the 15- to 30-mm-sized ameboid form of Naegleria fowleri penetrates the brain via the nose, causing amebic meningoencephalitis.^16 Affected individuals typically present with the disease after contact with contaminated freshwater bodies or after rinsing the nose with nonsterile tap water.^17 Furthermore, the permeability of this barrier has been evoked as a possible quicker and safer drug delivery route to the brain,^18^,19 as well as access to cerebrospinal fluid through nasal lymphatic vessels.^20 In this study, given the ubiquitous presence of MPs in the air^21 and their previous identification in the human nasal cavity,^22^,23 we hypothesized that the smallest-size fraction of MPs could reach the OB. Therefore, we conducted an investigation into the presence of MPs within human OB obtained from 15 deceased individuals during coroner autopsies. We identified and analyzed various characteristics of the MPs, including their size, morphology, color, and polymeric composition. Methods This case series study was approved by the ethical board of the Sao Paulo University Medical School, in compliance with the Helsinki Declaration. Written informed consent was provided by the deceased individuals' next of kin. The study was conducted from February 2023 to May 2024 and followed the Reporting Guideline for Case Series.^46 Study Population We obtained the bilateral OBs from 15 adult individuals who underwent routine coroner autopsies at the Sao Paulo City Death Verification Service of University of Sao Paulo to determine the cause of death. All individuals had been residents of Sao Paulo for more than 5 years. Cases in which the deceased had previously undergone neurosurgical interventions were not selected for the study. Information regarding previous occupations and underlying diseases was obtained through questionnaires administered to the next of kin. Additionally, autopsy reports were reviewed. We also collected samples from the OB of 2 stillbirths at 7 months gestation, as a negative control for the study. The collection of OBs took place between February 2023 and February 2024. Quality Control and Quality Assurance and Evaluation of Sample Processing We implemented a plastic-free approach to safeguard the integrity of our results. This strategy facilitated a thorough assessment of potential sources of variability and error, thereby enhancing the reliability of our collected data. All procedures, from the OB sampling to the micro-Fourier transform infrared (mFTIR) spectroscopy analysis, followed the protocols recommended by several studies.^24^- 26 Briefly, all solutions were prefiltered through a Whatman cellulose filters with a mesh size of 0.45 mm. Stainless steel materials, glassware, and samples were covered with aluminum foil (before and after processing) to avoid airborne sample contamination. Ultrapure water with a resistivity of 18.2 mO was obtained from a Milli-Q purification device (Millipore Corp). Glass and stainless-steel materials were washed thoroughly using the purified water 3 times and then using acetone P.A. to remove any particles or fibers that have adhered to the glass. The scientific staff responsible for handling samples wore exclusively 100% cotton laboratory coats and were required to remove any plastic or textile bracelets, rings, and watches to minimize the risk of sample contamination. Clean latex gloves were used for all procedures. The samples were processed in a clean laminar flow cabinet (ISO class 5, SKU330313, Hipperquimica, SP, Brazil). Blank filters (47 mm) were used from the OB collection to the sample filtering to assess possible airborne contamination. A clean filter was also used as a negative control. Access to the mFTIR spectroscopy and the digestion/ filtration room was restricted to the operators only, to avoid air flow in the room and the suspension/resuspension of possible atmospheric contaminants. Sample Processing The presence of MPs in the OB was assessed in 2 ways: directly on the tissue and a digested assessment. The cryo-cuts method preserves the spatial context of MPs within the tissue, allowing their proximity to anatomical structures such as blood vessels to be observed. This is crucial for understanding potential pathways of MPs translocation and accumulation within the OB. The digestion method ensures that MPs that are deeply embedded in the tissue are not overlooked. Postdigestion, MPs are concentrated on filters, which can then be analyzed for a more accurate quantification and identification without interference from the tissue matrix. By combining these 2 methods, the study maximized the probability of detecting and characterizing MPs within the OB. OB Cryo-Cuts The left OB of each case was horizontally cryo-sectioned using a Leica CM1860 UV cryostat (Leica Biosystems) at 10 mm thickness and thaw-mounted onto 5 mm x 5 mm gold/chromium-coated silicon dioxide/ silicon substrates. No fixatives were used for the tissue sections. The samples were then freeze-dried for 48 hours (Freezone 6 [Labconco Corp]) and examined by optical microscopy (Eclipse LV100ND [Nikon Instruments Inc]). The freeze-drying process maintains the integrity of biological tissues by extracting water without substantially compromising their structure. Futhermore, the presence of water molecules, characterized by strong hydrogen bonding, poses a considerable challenge in FTIR measurements, as they mask specific signals indicative of chemical compositions.^27 The procedures took place in a biosafety level 2 room in the Cryogenic Preparations Laboratory (LCRIO) at the Brazilian Synchrotron Light Laboratory (LNLS), National Center for Energy and Materials Research (CNPEM). Sample Digestion and Filtering Immediately after sampling, the right OBs from 10 selected cases were individually frozen at -20 degC in glass vials, covered with aluminum foil, and sealed with a glass lid until the digestion. For 5 patients, there was no available tissue for digestion. The tissues were then incubated for 12 hours at 40 degC using the enzyme mixture Corolase 7089 (20 UHb/mL)^4 inside the laminar flux hood. The solution was then filtered using a glass vacuum filtration system (Sigma-Aldrich) and silver membrane filters (25 mm in diameter and 0.45 microns pore size [Millipore]). Subsequently, the filters were kept individually in closed Petri dishes inside a glass dissector until the spectroscopy analysis. Due to the material characteristics, a recovery test was not feasible. Micro-Fourier Transform Infrared Spectroscopy We performed single-point mFTIR microspectroscopy measurements in reflection mode using a diffraction-limited IR microscope (Cary 620 [Agilent Technologies]). The IR microscope is coupled to a Michelson interferometer responsible for the frequency demultiplexing of the mid-IR broadband response. We used a 1000 K Globar source and illumination and interferograms detection was done by using a high-sensitivity cryo-cooled Mercury-Cadmium-Telluride (MCT [Infrared Associates Inc]). After the interferometer, the IR beam was directed to a 25 x objective that produced an illumination spot of 420 mm x 420 mm on the sample's surface. This field of view was further reduced to 50 to 100 mm by slits to concentrate the analysis around specific particles. The reflected light was collected through a confocal arrangement by the same objective lens and then directed to the MCT detector. FTIR spectra were generated by calculating the Fourier transforms of the recorded interferograms. The spectral resolution was configured at 16 cm^-1, encompassing the range from 4000 to 700 cm^-1. Each mFTIR spectrum was normalized to the spectrum of a clean gold surface, which served as a reference background. The cryo-cuts and digested filters were fully analyzed. The mFTIR analyses took place in the IMBUIA beamline at the Brazilian Synchrotron Light Laboratory (LNLS), National Center for Research in Energy and Materials (CNPEM). The acquired spectra were processed manually using the KnowItAll Informatics System 2024 (John Wiley and Sons Inc). The comparative analysis was performed with the help of FTIR spectra libraries developed for MPs research, including the FTIR Library of Plastic Particles (FLOPP),^28 FTIR Library of Plastic Particles Sourced from the Environment (FLOPP-e),^28 siMPLe database,^29 and KnowItAll IR Spectral Library. We adopted a Hit Quality Index greater than 75% of agreement between characteristic bands of polymers observed in reference materials with bands observed in unknown particles or fibers.^30^,31 Microphotograph Analysis We determined particle sizes by analyzing microphotographs obtained through mFTIR spectroscopy. ImageJ 1.54g software (US National Institutes of Health) was used for accurate measurements. Statistical Analysis Descriptive analyses were performed using SPSS Statistics 26.0 software (IBM Inc). These analyses were performed in April 2024. Results The median (range) age of the 15 deceased individuals was 69.5 (33-100) years. They included 12 males and 3 females. Demographic information is detailed in Table 1. Apart from the 2 cases with histological evidence of previous ischemic cerebral infarction and 1 case with a subarachnoid hematoma due to a ruptured aneurysm of the middle cerebral artery, there were no cerebral histological abnormalities in the remaining cases. The mean (SD) mass of the OB (left or right) was 0.187 (0.050) g, ranging from 0.100 to 0.273 g. A total of 16 synthetic polymer particles and fibers were identified in 8 out of the 15 deceased individuals, with a range from 1 to 4 MPs per OB. Of these, 75% were particles, of which 83.4% were fragments and 16.6% were spheres, while 25% were fibers with a length-to-width ratio exceeding 3. The particles had a mean (SD) length of 12.1 (7.2) mm, ranging from 5.5 to 26.4 mm, and a mean (SD) width of 8.9 (6.4) mm, ranging from 3.0 to 25.4 mm. The fibers exhibited a mean (SD) length of 21.4 (2.6) mm, ranging from 19.0 to 24.5 mm, and a mean (SD) width of 3.8 (1.8) mm, ranging from 3.0 to 6.0 mm. In the procedural blank filters, we detected 2 cotton fibers, 2 silica beads, and 1 silicate fragment. Polymeric materials were absent in both the procedural blank and negative control filters. From the 2 collected samples in stillborn, we were able to analyze 1 case, which did not show the presence of MPs. The other case had insufficient material for analysis. Polypropylene was the most prevalent polymer (43.8%), followed by polyamide, nylon, and polyethylene vinyl acetate (12.5%). This was followed by polyethylene, perlon polyamide, and wool-polypropylene, which accounted for 6.3%). Upon comparison with the reference spectral library of plastic materials, the identified MP particles and fibers exhibited indications of weathering. The mFTIR spectra of the weathered MPs differed substantially from those of pristine standard samples; multiple peaks in the spectra of weathered MPs were attenuated or entirely absent. Microphotographs and mFTIR point-spectra showing the main types of MP detected in the OB are shown in Figure 1 and Figure 2. The complete mFTIR point-spectra results of the digested OB are presented in the eFigure in Supplement 1. Table 2 provides details regarding the morphology, color, and chemical characterization of the particles and fibers. Discussion To our knowledge, this is the first study in which the presence of MPs in the human brain was identified and characterized using mFTIR, allowing quantification and characterization of the morphology and polymeric matrix. Specifically, we detected particles as the predominant shape in the OB in 8 out of 15 individuals who underwent autopsy in Sao Paulo. Our data extend the notion that not only black carbon^15 but also MP accumulate in the OB in humans. We believe that the anatomy of the cribriform plate of the ethmoid bone may serve as a gateway in the nasal passages from within the skull. This plate, situated between the frontal and sphenoid bones, lies horizontally and contains multiple foramina, each less than 1 mm in diameter.^32 The OB lies directly above it, and the olfactory neurons of the nasal mucosa reach the OB via the foramina of the cribriform plate. Recent studies have shown that part of the cerebrospinal fluid outflow occurs via lymphatic vessels that surround the olfactory axons, reaching the nasal mucosa and extending toward the nasal lymphoid tissue.^33 Ossification of the CP occurs by 1 year of age,^34 and the total area of the perforations is age-dependent; it is 3.79 to 3.99 mm^2 in those over 50 years of age and 5.61 to 7.91 mm^2 in those under 50 years of age. This decrease in the area over time, causing compression and dysfunction of the olfactory nerves, is thought to explain the decreased olfactory sensation in older individuals.^35 Furthermore, in mice, paracellular spaces in the olfactory epithelium can reach 5 to 20 mm in the medial-lateral dimension of the transport and a 10- to 100-mm range observed in the rostral-caudal dimension.^36 If a similar situation is observed in humans, this could represent another factor facilitating entry of larger particles in the brain via the cribriform plate. Given the widespread presence of MPs in the air, some of which are associated with PM[2.5],^37 the identification of MPs in the nose^45 and now in the OB, along with the vulnerable anatomical pathways, reinforces the notion that the olfactory pathway is an important entry site for exogenous particles to the brain. In previous epidemiological studies, exposure to PM[2.5] has been associated with neurological and psychiatric adverse outcomes, such as dementia.^38^, 39 Some neurodegenerative diseases, such as Parkinson disease, seem to have a connection with nasal abnormalities as initial symptoms.^40 In experimental studies, both exposures to PM[2.5] and MPs have shown to cause several neurotoxic effects, including disturbances on the brain development.^41^,42 The cribriform plate reaches maturation at 1 to 2 years of age, which is a critical time window during which MP penetration into the brain could have negative effects on the organ maturation. In this study, the MP polymeric matrix found in the OB corresponds to the most produced and manufactured plastics, such as polypropylene, nylon/polyamide, polyethylene and polyethylene vinyl acetate, present in packaging, clothes and home accessories, suggesting indoor environments as a major source of inhaled MPs.^21^,43 Limitations This study has certain limitations. Although the olfactory pathway seems a likely exposure route, we cannot dismiss the possibility of multiple entry routes. MPs might have reached the OB either through systemic circulation, crossing the BBB, or via the respiratory pathway through the trigeminal nerve.^44 The biologic matrix of the OB tissues can be a confounding factor when analyzing MP spectra due to its similarity to some polymeric materials. Therefore, we were cautious to consider suspect particles as polymeric material only when spectral bands highly matched with weathered bands from MP libraries (HQI >75%). In the filtered samples, the biological matrix was previously digested, not being an issue. Given the maximum spatial resolution (3 mm) of mFTIR spectroscopy setup and the limited capacity of analysis for other techniques, we were unable to detect nanoplastics. It is likely that the number of plastics in the submicron range with the potential to cause substantial biological damage would be far more numerous. Avoiding contamination is one of the biggest challenges when analyzing MP. Due to the presence of MP fibers and particles in the air, we have used blank samples in all methodological procedures to detect contamination of the air. We found no MP in our procedural blanks, which supports the validity of our results. Furthermore, we had the opportunity to analyze the brains of 2 stillbirths. However, the status of brain tissue maceration made the analysis challenging due to difficulties in sampling and processing. Conclusions This case series describes the presence of MPs in the OB, mainly particles of the most commonly produced/processed polymers for clothing and packaging such as polypropylene and nylon. Our data support the idea that the olfactory pathway is an important entry site for environmental air pollutants. Considering the potential neurotoxic effects caused by MPs in the brain, and the widespread environmental contamination with plastics, our results should raise concern in the context of increasing prevalence of neurodegenerative diseases. Noninvasive imaging technologies, such as magnetic resonance imaging, are needed to overcome the current limitations in tissue analysis of different human organs and to improve the understanding of the health hazards of MPs. Back to top Article Information Accepted for Publication: August 22, 2024. Published: September 16, 2024. doi:10.1001/jamanetworkopen.2024.40018 Open Access: This is an open access article distributed under the terms of the CC-BY License. (c) 2024 Amato-Lourenco LF et al. JAMA Network Open. Corresponding Author: Luis Fernando Amato-Lourenco, PhD, Freie Universitat Berlin - Institut fur Biologie, Altensteinstr 6D- 14195 Berlin, Germany (luisfamato@zedat.fu-berlin.de). Author Contributions: Dr Amato-Lourenco and Prof Mauad had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Amato-Lourenco, Carvalho-Oliveira, Mauad. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Amato-Lourenco, Dantas, Carvalho-Oliveira, Mauad. Critical review of the manuscript for important intellectual content: Amato-Lourenco, Ribeiro Junior, Ribeiro Paes, S. Rabelo, da Costa, Ando, Freitas, Bispo, Carvalho-Oliveira, Mauad. Statistical analysis: Amato-Lourenco, Freitas, Mauad. Obtained funding: Amato-Lourenco, Mauad. Administrative, technical, or material support: Amato-Lourenco, Dantas, Ribeiro Paes, Freitas, Bispo, Carvalho-Oliveira. Supervision: Amato-Lourenco, Carvalho-Oliveira, Mauad. Conflict of Interest Disclosures: None reported. Funding/Support: This study was financially supported by the Alexander von Humboldt Foundation (AvH), Germany, by the Plastic Soup Foundation, by the Brazilian Research Council (CNPq) grant 308023/ 2023-4 and Sao State Research Agency (FAPESP) grant 2021/10724-2. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Data Sharing Statement: See Supplement 2. Additional Contributions: We would like to thank the Sao Paulo City Death Verification Service (SVOC) staff, the IMBUIA beamline at the Brazilian Synchrotron Light Laboratory (LNLS) for providing beamtime (proposal No. 20232740) and the technical support, Maria Westerbos and the Plastic Soup Foundation, Professor Dr Lukas Kenner and Professor Dra Verena Pichler for reviewing the manuscript before submission, and to Dr Walter Waldman for recommending the LNLS facilities to us. They were not compensated. References 1. Li Y, Tao L, Wang Q, Wang F, Li G, Song M. Potential health impact of microplastics: a review of environmental distribution, human exposure, and toxic effects. Environ Health. 2023;1 (4):249-257. doi:10.1021/envhealth.3c00052Google ScholarCrossref 2. Marfella R, Prattichizzo F, Sardu C, et al. Microplastics and nanoplastics in atheromas and cardiovascular events. N Engl J Med. 2024;390(10):900-910. doi:10.1056/NEJMoa2309822PubMedGoogle Scholar Crossref 3. 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