Bridging Preclinical and Clinical Perspectives: New Insights on Melatonin’s Neuroprotective Effects in Neonatal Rats with Hypoxic-Ischemic Brain Injury and Discovering Prognostic Biomarkers in Patients with Traumatic Brain Injury

This thesis represents a comprehensive endeavor to bridge preclinical and clinical research, aiming to enhance our understanding and treatment approaches for brain injuries. It focuses on two specific areas: neonatal hypoxic-ischemic (HI) brain injury and traumatic brain injury (TBI). The thesis had a dual aim: first, to elucidate the neuroprotective mechanisms of melatonin in neonatal HI brain injury using a neonatal rat model of HI, and second, to identify prognostic biomarkers in patients with TBI. The thesis includes two main chapters. The first chapter, titled “Neonatal Hypoxic-Ischemic Brain Injury: Involvement of Notch1 Signaling Pathway and SIRT3 in the Neuroprotective Effect of Melatonin,” was conducted at the University of Urbino Carlo Bo, Italy. This study demonstrated how melatonin, a natural neurohormone, attenuated brain damage in neonatal HI by modulating the Notch1 signaling pathway and SIRT3. These findings offer new insights into the potential therapeutic role of melatonin in neonatal brain injuries. The second chapter, “Traumatic Brain Injury: Identification of Prognostic Biomarkers,” was conducted during my research at The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, Canada. This chapter includes two projects. The first project, “A Canadian Biobank and Database for Traumatic Brain Injury (CanTBI),” aimed to establish a comprehensive national database, linking regional biobanks and facilitating the translation of molecular biomarker research into clinical practice. The second project, “Prognostic Serum Protein Biomarkers in Children with Severe Traumatic Brain Injury,” discovered eight prognostic biomarkers. This discovery opens avenues for enhanced clinical monitoring and risk stratification in TBI patients, potentially guiding the development of novel treatment strategies. In summary, this thesis not only increases our understanding of brain injuries but also lays the foundation for future research in this field. It highlights the shared pathophysiological mechanisms in HI brain injury and TBI and proposes innovative diagnostic and therapeutic strategies.