Grantor: Croatian Science Foundation
Grantor’s website: https://hrzz.hr/en/
Project ID: IP-2019-04-1511
Project duration: 1 January 2020 – 31 December 2023
Total funding: 150.348,40 EUR
Principal investigator: Assoc. Prof. Kristina Grabušić, PhD
Department of Physiology, Immunology and Pathophysiology, Faculty of Medicine, University of Rijeka, Croatia
Research team
| Vedrana Krušić Alić | Department of Physiology, Immunology and Pathophysiology, Faculty of Medicine, University of Rijeka, Croatia |
| Lara Valenčić Seršić | Department of Anaesthesiology, Resuscitation, Emergency and Intensive Care Medicine, Faculty of Medicine, University of Rijeka, Croatia |
| Siniša Zrna | General Hospital Pula, Croatia |
| Janja Tarčuković | Department of Anaesthesiology, Resuscitation, Emergency and Intensive Care Medicine, Faculty of Medicine, University of Rijeka, Croatia |
| Tin Jagoić | Department of Physiology, Immunology and Pathophysiology, Faculty of Medicine, University of Rijeka, Croatia |
| Mladenka Malenica | Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Croatia |
| Ksenija Tulić | Department of Physiology, Immunology and Pathophysiology, Faculty of Medicine, University of Rijeka, Croatia |
| Maša Biberić | General Hospital Pula, Croatia |
| Vlatka Sotošek | Department of Anaesthesiology, Resuscitation, Emergency and Intensive Care Medicine, Faculty of Medicine, University of Rijeka, Croatia |
| Natalia Kučić | Department of Physiology, Immunology and Pathophysiology, Faculty of Medicine, University of Rijeka, Croatia |
| Olga Shevchuk | Medical Research Centre, University Hospital Essen, Germany |
| Jelena Marinić | Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Croatia |
| Simone Dal Zilio | Istituto Officina dei Materiali – CNR-IOM, Trieste, Italy |
| Lada Kalagac Fabris | General Hospital Pula, Croatia |
| Aleksandar Šuput | General Hospital Pula, Croatia |
Brief description
The CirBrain proposal intends to identify biomarkers of neurorecovery in patients with severe traumatic brain injury (TBI). Severe TBI is intracranial damage caused by the impact on the head leading to coma and a possible fatal outcome. Despite the severity of the injury, a complete neural recovery is possible. However, it is not known when brain recovery is initiated and how it might be affected by therapeutic interventions since knowledge about neurorecovery biomarkers is lacking.
The major goal of CirBrain is to enable the monitoring of brain recovery by biomarkers in body fluids. CirBrain is strongly supported by the latest studies in animals showing that the adult mammalian brain modifies levels of neuro regenerative signals in cerebrospinal fluid (CSF). Moreover, our published and preliminary post-TBI analyses of human CSF describe early induction of:
i) extracellular vesicles (EVs), membrane-enveloped particles derived from cells and able to transport proteins and nucleic acids
ii) novel neuroregeneration-associated proteins.
Based on these results, CirBrain aims to determine a more precise CSF kinetics of changes in:
1) EV size and number by tunable resistive pulse sensing
2) EV morphology and protein content by immunogold staining and electron microscopy
3) EV subpopulations by size-exclusion chromatography followed by slot-blot immunoanalysis
4) levels of neuroregeneration-associated proteins by targeted mass spectrometry
5) microRNA content by real-time PCR.
The biomarkers with the highest CSF levels detected in the first phase will be further analyzed in plasma as part of the second CirBrain phase. CirBrain is expected to give new insights into the identity and kinetics of circulating biomarkers for neurorecovery after TBI. Moreover, biomarkers based on CSF and blood might enable non-invasive monitoring of neurorecovery not only in TBI but also in diverse brain pathologies, providing evaluation of how different treatments affect brain recovery.