Microplastics in Brain Hematomas and Neurological Outcomes After Intracerebral Hemorrhage (PARTENOPE)

Plastic Accumulation in Residual Brain Tissues From Hemorrhagic Events: Neurological Outcomes and Pathogenetic Evidence (PARTENOPE Study)

This observational study investigates the presence of micro- and nanoplastics in surgically removed intracerebral hematomas and their association with neurological outcomes in patients with spontaneous intracerebral hemorrhage.

Microplastics have recently been identified in human tissues and are increasingly recognized as potential contributors to inflammation and vascular dysfunction. However, their role in cerebrovascular diseases, particularly intracerebral hemorrhage, remains unknown.

Patients undergoing surgical hematoma evacuation will be enrolled. Brain tissue and blood samples will be analyzed using advanced spectroscopic and imaging techniques to detect and characterize micro- and nanoplastics.

The study aims to evaluate whether the presence of these particles is associated with increased inflammation, worse neurological outcomes, and higher risk of adverse cerebrovascular events.

This research may provide novel insights into the impact of environmental pollutants on brain vascular disease and patient prognosis.

Study Overview

• Status: Active, not recruiting
• Conditions: Intracerebral Hemorrhage; Brain Hematoma
• Intervention / Treatment: Other: Observational Analysis

Detailed Description

Spontaneous intracerebral hemorrhage is a severe and life-threatening neurological condition representing approximately 10-15% of all strokes worldwide and is associated with high early mortality and substantial long-term disability. Despite significant advances in neuroimaging, neurosurgical techniques, and neurocritical care, clinical outcomes remain poor, and the biological mechanisms underlying hemorrhage initiation, expansion, and secondary brain injury are still incompletely understood.

The pathophysiology of intracerebral hemorrhage is characterized by a complex interplay of vascular, inflammatory, and neurotoxic processes. Structural vascular alterations, endothelial dysfunction, and disruption of the blood-brain barrier contribute to vessel rupture and hematoma formation. Following the initial bleeding event, secondary brain injury is driven by hematoma-induced mechanical damage, oxidative stress, activation of resident and infiltrating immune cells, and release of pro-inflammatory mediators. Microglial activation, macrophage infiltration, and inflammasome-related pathways are recognized as important contributors to neuronal injury and neurological deterioration.

While traditional risk factors such as hypertension and small vessel disease are well established, the contribution of environmental exposures to cerebrovascular vulnerability has been largely overlooked. In recent decades, environmental exposure to micro- and nanoplastics has emerged as a global health concern. The exponential increase in plastic production has resulted in widespread distribution of plastic-derived particles across ecosystems, leading to chronic human exposure through ingestion, inhalation, and dermal contact.

Microplastics and nanoplastics have been detected in multiple biological matrices, including blood, lung tissue, placenta, and cardiovascular structures. Experimental and translational studies suggest that these particles may interact with biological systems by promoting oxidative stress, immune activation, endothelial dysfunction, and tissue inflammation. Microplastics and nanoplastics have also been described in vascular tissues, supporting the rationale for investigating their potential association with cerebrovascular disease.

The central nervous system is particularly susceptible to vascular and inflammatory insults, and preservation of blood-brain barrier integrity plays a critical role in maintaining neural homeostasis. Emerging evidence indicates that nanoscale particles may cross biological barriers and potentially contribute to neuroinflammation, microglial activation, and neuronal dysfunction. However, the presence, distribution, and potential biological impact of microplastics and nanoplastics in cerebrovascular diseases, particularly intracerebral hemorrhage, have not been systematically investigated.

The PARTENOPE study (Plastic Accumulation in Residual Brain Tissues from Hemorrhagic Events: Neurological Outcomes and Pathogenetic Evidence) has been designed to address this knowledge gap. This observational cohort study integrates retrospective and prospective data collection and adopts a translational approach combining clinical characterization, advanced analytical chemistry, and biological investigation.

Study Design and Population

The study includes adult patients diagnosed with spontaneous intracerebral hemorrhage undergoing neurosurgical hematoma evacuation. Both retrospectively identified cases and prospectively enrolled patients are included to capture a broad spectrum of clinical presentations and improve the robustness and generalizability of findings.

Patients with traumatic intracranial hemorrhage, intracranial neoplasms, or vascular malformations are excluded to ensure a homogeneous population focused on primary spontaneous hemorrhagic events.

Biological Sample Collection and Contamination Control

Intracerebral hematoma samples are collected intraoperatively using standardized protocols specifically designed to minimize environmental contamination. Measures include the use of non-plastic surgical instruments, glass collection systems, and controlled laboratory environments to preserve sample integrity and minimize external contamination.

Peripheral blood samples are obtained to assess systemic exposure to microplastics and nanoplastics and to enable comparative analyses between circulating and tissue-associated particle burden.

Analytical Characterization of Microplastics and Nanoplastics

Identification and characterization of microplastics and nanoplastics are performed using a multimodal analytical platform integrating advanced spectroscopic and imaging techniques. These techniques include scanning electron microscopy with energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, and pyrolysis gas chromatography-mass spectrometry.

This integrated analytical approach enables high-resolution characterization of particle size, morphology, and polymer composition. Quantitative analyses provide estimates of particle burden within hematoma tissue, while qualitative analyses identify polymer types and potential environmental sources.

Spatial mapping analyses are also conducted to determine localization of particles within the hematoma matrix, including their presence in extracellular compartments and their potential interaction with inflammatory cells such as macrophages.

Clinical and Radiological Characterization

Comprehensive clinical data are collected, including demographic variables, cardiovascular risk factors, medication exposure, and comorbid conditions. Radiological assessment includes hematoma volume, location, and imaging characteristics derived from computed tomography and magnetic resonance imaging.

Perioperative variables, surgical techniques, and postoperative management are also recorded to enable integrated analysis of clinical and biological determinants of outcome.

Outcome Assessment

Patients are followed longitudinally to evaluate neurological and clinical outcomes using standardized clinical, radiological, and biological assessments.

Primary and Secondary Objectives

The primary objective of the study is to evaluate the presence and burden of microplastics and nanoplastics in intracerebral hematoma tissue and to investigate their association with neurological and cerebrovascular outcomes.

Secondary objectives include:

• evaluating the relationship between circulating and tissue-associated particle levels
• assessing the association between particle burden and inflammatory responses
• exploring the potential contribution of microplastics and nanoplastics to hematoma progression and recurrence
• characterizing the physicochemical properties and distribution of detected particles

Mechanistic and Exploratory Analyses

Exploratory analyses aim to investigate potential mechanistic pathways linking microplastic and nanoplastic exposure to neurovascular injury. These include evaluation of oxidative stress pathways, immune cell activation, endothelial dysfunction, and inflammatory signaling cascades.

Particular attention is given to macrophage activation, microglial response, and inflammasome-related pathways that may contribute to secondary brain injury after hemorrhage. The interaction between microplastics and nanoplastics and the blood-brain barrier is also explored, including their potential contribution to barrier dysfunction and increased vascular permeability.

Scientific and Clinical Implications

The PARTENOPE study represents one of the first systematic investigations of microplastics and nanoplastics in intracerebral hemorrhage. By integrating environmental exposure science with clinical neurology and advanced analytical techniques, this study aims to provide novel insights into the potential role of environmental pollutants in cerebrovascular disease.

If an association between microplastic and nanoplastic accumulation and adverse clinical outcomes is identified, these findings may have important implications for risk stratification, prevention strategies, and future research on environmental determinants of neurological disease.

Ultimately, this study seeks to contribute to a more comprehensive understanding of the factors influencing cerebrovascular health and disease progression.

• Study Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy, 80138
    • University Hospital Luigi Vanvitelli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with spontaneous intracerebral hemorrhage undergoing surgical hematoma evacuation at a tertiary care hospital. The cohort includes both retrospective and prospective cases, enabling integrated clinical, radiological, and biological analyses.

Description

Inclusion Criteria:

• Age ≥18 years
• Diagnosis of spontaneous intracerebral hemorrhage confirmed by CT or MRI
• Indication for surgical hematoma evacuation
• Availability of intracerebral hematoma tissue sample
• Ability to provide informed consent (patient or legal representative)

Exclusion Criteria:

• Traumatic intracerebral hemorrhage
• Intracranial neoplasms
• Known vascular malformations (e.g., arteriovenous malformations, aneurysms)
• Severe systemic infection or sepsis at admission
• Inadequate or contaminated biological samples
• Refusal or inability to provide informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Intracerebral Hemorrhage Patients; Patients with spontaneous intracerebral hemorrhage undergoing surgical hematoma evacuation. Micro- and nanoplastics will be measured in hematoma tissue and blood samples, and associations with clinical outcomes will be evaluated.

Other: Observational Analysis; No intervention is administered as part of the study. All patients receive standard clinical care according to current guidelines for intracerebral hemorrhage. Biological samples, including intracerebral hematoma tissue and peripheral blood, are collected for observational analysis of micro- and nanoplastics and their association with clinical, radiological, and biological outcomes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of Micro- and Nanoplastics in Intracerebral Hematoma Tissue	Quantification of micro- and nanoplastics in intracerebral hematoma tissue samples collected during surgical evacuation.	Baseline (intraoperative sampling)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale Score	Neurological outcome assessed using the modified Rankin Scale, a 7-point functional outcome scale ranging from 0 (no symptoms) to 6 (death), where higher scores indicate worse neurological disability.micro- and nanoplastic burden.	12 months
Circulating Concentrations of Inflammatory Biomarkers	Measurement of circulating inflammatory biomarkers, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and their association with micro- and nanoplastics.hematoma tissue samples collected during surgical evacuation. Neurological outcome will be assessed using the modified Rankin Scale (mRS), a 7-point functional outcome scale ranging from 0 (no symptoms) to 6 (death), where higher scores indicate worse neurological disability.	Baseline
Concentration of Circulating Micro- and Nanoplastics	Concentration of circulating micro- and nanoplastics measured in peripheral blood samples and evaluated in relation to micro- and nanoplastic burden in intracerebral hematoma tissue.	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematoma Volume	Measurement of intracerebral hematoma volume assessed by CT imaging and its association with micro- and nanoplastic burden.	Baseline

Collaborators and Investigators

• Sponsor: University of Campania Luigi Vanvitelli
• Collaborators: Federico II University; IRCCS Multimedica

Publications and helpful links

General Publications

• Prattichizzo F, Ceriello A, Pellegrini V, La Grotta R, Graciotti L, Olivieri F, Paolisso P, D'Agostino B, Iovino P, Balestrieri ML, Rajagopalan S, Landrigan PJ, Marfella R, Paolisso G. Micro-nanoplastics and cardiovascular diseases: evidence and perspectives. Eur Heart J. 2024 Oct 7;45(38):4099-4110. doi: 10.1093/eurheartj/ehae552.
• Marfella R, Kallweit U. Neurotoxicity at the Tides: A Call to Action on Marine Microplastics and Brain Health. Eur J Neurol. 2025 May;32(5):e70181. doi: 10.1111/ene.70181. No abstract available.
• Marfella R, Prattichizzo F, Paolisso G. Microplastics and nanoplastics: tiny threats for cardiovascular diseases? Cardiovasc Res. 2025 Oct 24;121(12):1793-1795. doi: 10.1093/cvr/cvaf143. No abstract available.
• Marfella R, Carreras F, Prattichizzo F, La Grotta R, Pellegrini V, Sardu C, D'Onofrio N, Barbieri M, Municino M, Siniscalchi M, Spinetti F, Vigliotti G, Vecchione C, Carrizzo A, Accarino G, Squillante A, Spaziano G, Mirra D, Esposito R, Fenti A, Galoppo S, Canzano S, Marfella LV, Falco G, Balestrieri ML, Mauro C, Ceriello A, Landrigan PJ, D'Agostino B, Iovino P, Paolisso G. Detection and Proinflammatory Effects of BTEX within the Human Atherosclerotic Plaque. Environ Sci Technol. 2025 Dec 23;59(50):27044-27056. doi: 10.1021/acs.est.5c04941. Epub 2025 Dec 11.
• D'Onofrio N, Donisi I, Del Vecchio V, Prattichizzo F, Pellegrini V, Barbieri M, Ceriello A, Marfella R, Paolisso G, Balestrieri ML. PCSK9 inhibition ameliorates microplastic-induced endothelial redox imbalance via SIRT6 modulation. Cell Mol Biol Lett. 2025 Dec 22;31(1):9. doi: 10.1186/s11658-025-00838-z.
• Marfella R, Prattichizzo F, Barbieri M, Paolisso P, Scisciola L, Basilicata MG, Marfella LV, Pesapane A, Fenti A, La Grotta R, Carreras F, Iovino P, Barbato E, Ceriello A, Landrigan PJ, Paolisso G. Microplastics and Atherosclerosis: Mechanisms. Annu Rev Pharmacol Toxicol. 2026 Jan;66(1):369-390. doi: 10.1146/annurev-pharmtox-062124-113011.
• Donisi I, Sardu C, Colloca A, Balestrieri A, Vecchio VD, Marfella R, Campanile G, D'Onofrio N, Balestrieri ML. In vitro evidence and integrative bioinformatics identify the SGLT2-PPARgamma axis as a target against polyethylene microplastic-driven metabolic reprogramming in colorectal cancer cells. J Transl Med. 2026 Feb 2;24(1):312. doi: 10.1186/s12967-026-07776-0.
• Prattichizzo F, Paolisso G, Iovino P, Marfella R. Microplastics and nanoplastics: Novel components of the environmental exposome associated with cardiovascular diseases. Trends Cardiovasc Med. 2026 Mar 12:S1050-1738(26)00038-1. doi: 10.1016/j.tcm.2026.03.003. Online ahead of print. No abstract available.
• Marfella R, Fumagalli C, Marfella LV, Furbatto F, Fenti A, Paolisso P, Sardu C, Prattichizzo F, Iovino P, Mauro C. Environmental Pollutant-Induced Cardiopathogenesis Through Immune Dysfunction: The Emerging Role of Micro- and Nanoplastics. Can J Cardiol. 2026 Apr 8:S0828-282X(26)00300-4. doi: 10.1016/j.cjca.2026.03.050. Online ahead of print.
• 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 May;163:107199. doi: 10.1016/j.envint.2022.107199. Epub 2022 Mar 24.
• Marfella R, Prattichizzo F, Sardu C, Fulgenzi G, Graciotti L, Spadoni T, D'Onofrio N, Scisciola L, La Grotta R, Frige C, Pellegrini V, Municino M, Siniscalchi M, Spinetti F, Vigliotti G, Vecchione C, Carrizzo A, Accarino G, Squillante A, Spaziano G, Mirra D, Esposito R, Altieri S, Falco G, Fenti A, Galoppo S, Canzano S, Sasso FC, Matacchione G, Olivieri F, Ferraraccio F, Panarese I, Paolisso P, Barbato E, Lubritto C, Balestrieri ML, Mauro C, Caballero AE, Rajagopalan S, Ceriello A, D'Agostino B, Iovino P, Paolisso G. Microplastics and Nanoplastics in Atheromas and Cardiovascular Events. N Engl J Med. 2024 Mar 7;390(10):900-910. doi: 10.1056/NEJMoa2309822.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Actual): January 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Neuroinflammation; Environmental Exposure; Microplastics; Blood-Brain Barrier; Nanoplastics
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hemorrhage; Inflammation; Intracranial Hemorrhages; Pathological Conditions, Signs and Symptoms; Neuroinflammatory Diseases; Cerebral Hemorrhage
• Other Study ID Numbers: PARTENOPE-ICH-01; DAMSS-CIAMC-2026 (Other Grant/Funding Number: University of Campania "Luigi Vanvitelli",)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) will be made available upon reasonable request after publication of the primary results. Data will be shared with qualified researchers for scientific purposes, subject to institutional approval and data sharing agreements.
• IPD Sharing Time Frame: De-identified individual participant data and supporting documents will be available beginning 6 months after publication of the primary results and will remain available for at least 5 years.
• IPD Sharing Access Criteria: Data will be available to qualified researchers with a scientifically sound research proposal. Requests will be reviewed by the study investigators and the institution. Data will be shared following approval and completion of a data sharing agreement to ensure confidentiality and appropriate use.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No