Identification of circulating biomarkers for neuro-recovery of brain-injured patients (CirBrain)
The CirBrain proposal intends to identify biomarkers of neurorecovery in patients with severe traumatic brain injury (TBI). Severe TBI is an intracranial damage caused by the impact on the head leading to coma and possible fatal outcome. Despite the severity of 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 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 neuroregenerative 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 puls 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 analysed in plasma as part of the second CirBrain phase.
CirBrain is expected to give new insights into 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.
