Stroke represents the second cause of death, after those related to cardiovascular diseases, and the first cause of disability in the world, with a prevalence that doubles with every decade of life after 55 years of age. The research activity was carried out directly on patients suffering from the disease. As a method of analysis, the patients' blood samples were used, obtained in a timely manner, starting from the acute phase of the disease (within 24 hours from the onset of symptoms) and then after 7 days, 30 days, 90 days up to 180 days during the post-ischemic period. The analyzes were conducted at the Laboratory of Nanomedicine and Molecular Imaging of the Maugeri Scientific Clinical Institutes and are part of an observational, longitudinal and prospective multicentre experimental study. The primary objective of the study is a targeted investigation of the evaluation and possible significance that some circulating biomarkers, present in peripheral blood, may have both in the acute post-stroke phase and in the course of the disease. The work carried out allowed us to quantify the serum levels of light chain neurofilaments (Nf-L) using SiMoA technology. The results obtained show that the serum levels of Nf-L increase in the acute phase of the disease, compared to healthy control subjects. In the second part of the thesis, a preliminary research was conducted by examining the variations in the plasma levels of some microRNA candidates, potentially involved in events that are triggered following ischemic stroke, such as for example post-ischemic excitotoxicity processes, neuroinflammation, of apoptosis, cell proliferation and processes triggered by hypoxia. The study of circulating biomarkers could help to better understand the molecular processes involved in ischemic damage and in the regulation of regenerative mechanisms. Furthermore, a correct and adequate forecast of the patient's motor and cognitive decline following ischemic stroke could make a significant contribution to prevention strategies, have a prognostic role and help the clinician to better set up rehabilitation treatments in order to make them more personalized and above all more objective, through the use of defined and reproducible parameters.
L’Ictus Cerebri rappresenta la seconda causa di decessi, dopo quelli riferiti alle patologie cardiovascolari, e la prima causa di disabilità nel mondo, con una prevalenza che raddoppia ad ogni decade di vita dopo i 55 anni di età. L’attività di Ricerca è stata attuata direttamente sui pazienti affetti dalla patologia. Come metodo di analisi sono stati utilizzati i prelievi ematici dei pazienti, reperiti in maniera puntuale, a partire dalla fase acuta di malattia (entro 24 ore dall’esordio dei sintomi) ed in seguito dopo 7 giorni, 30 giorni, 90 giorni fino a 180 giorni durante il periodo post-ischemico. Le analisi sono state condotte presso il Laboratorio di Nanomedicina ed Imaging Molecolare degli Istituti Clinici Scientifici Maugeri e si inseriscono nel contesto di uno studio sperimentale multicentrico di tipo osservazionale, longitudinale e prospettico. Obiettivo primario dello studio è una indagine mirata sulla valutazione e sul significato possibile che alcuni biomarcatori circolanti, presenti nel sangue periferico, possano avere sia in fase acuta post-ictus, sia nel decorso della patologia. Il lavoro svolto ha permesso di quantificare i livelli sierici dei neurofilamentia a catena leggera (Nf-L) tramite la tecnologia SiMoA. I risultati ottenuti mostrano che i livelli sierici di Nf-L aumentano nella fase acuta di malattia, in confronto a soggetti sani di controllo. Nella seconda parte della tesi è stata condotta una ricerca preliminare esaminando le variazioni nei livelli plasmatici di alcuni candidati microRNA, potenzialmente coinvolti in eventi che si innescano in seguito all’ictus ischemico, quali ad esempio processi di eccitotossicità post-ischemica, di neuro-infiammazione, di apoptosi, di proliferazione cellulare e processi innescati dall’ipossia. Lo studio dei biomarcatori circolanti potrebbe aiutare a comprendere meglio i processi molecolari coinvolti nel danno ischemico e nella regolazione dei meccanismi rigenerativi. Inoltre, una corretta ed adeguata previsione del declino motorio e cognitivo del paziente in seguito all’ictus ischemico potrebbe dare un contributo significativo alle strategie di prevenzione, avere un ruolo prognostico ed aiutare il clinico ad impostare al meglio i trattamenti riabilitativi nell’intento di renderli più personalizzati e soprattutto più oggettivi, mediante l’utilizzo di parametri definiti e riproducibili.
VALUTAZIONE QUANTITATIVA DI BIOMARCATORI EMATICI INDICATIVI DI DANNO ISCHEMICO CEREBRALE
CHIAVETTA, VIOLA
2020/2021
Abstract
Stroke represents the second cause of death, after those related to cardiovascular diseases, and the first cause of disability in the world, with a prevalence that doubles with every decade of life after 55 years of age. The research activity was carried out directly on patients suffering from the disease. As a method of analysis, the patients' blood samples were used, obtained in a timely manner, starting from the acute phase of the disease (within 24 hours from the onset of symptoms) and then after 7 days, 30 days, 90 days up to 180 days during the post-ischemic period. The analyzes were conducted at the Laboratory of Nanomedicine and Molecular Imaging of the Maugeri Scientific Clinical Institutes and are part of an observational, longitudinal and prospective multicentre experimental study. The primary objective of the study is a targeted investigation of the evaluation and possible significance that some circulating biomarkers, present in peripheral blood, may have both in the acute post-stroke phase and in the course of the disease. The work carried out allowed us to quantify the serum levels of light chain neurofilaments (Nf-L) using SiMoA technology. The results obtained show that the serum levels of Nf-L increase in the acute phase of the disease, compared to healthy control subjects. In the second part of the thesis, a preliminary research was conducted by examining the variations in the plasma levels of some microRNA candidates, potentially involved in events that are triggered following ischemic stroke, such as for example post-ischemic excitotoxicity processes, neuroinflammation, of apoptosis, cell proliferation and processes triggered by hypoxia. The study of circulating biomarkers could help to better understand the molecular processes involved in ischemic damage and in the regulation of regenerative mechanisms. Furthermore, a correct and adequate forecast of the patient's motor and cognitive decline following ischemic stroke could make a significant contribution to prevention strategies, have a prognostic role and help the clinician to better set up rehabilitation treatments in order to make them more personalized and above all more objective, through the use of defined and reproducible parameters.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/14453