Dottorato in ARTERIAL HYPERTENSION AND VASCULAR BIOLOGY

Titolo della tesi: SECONDARY BRAIN INJURY AFTER PARENCHYMAL CEREBRAL HEMORRHAGE IN HUMANS: THE ROLE OF NOX2-MEDIATED OXIDATIVE STRESS AND ENDOTHELIN-1

Spontaneous intraparenchymal cerebral hemorrhage (ICH) accounts for about 20% of all stroke cases and is associated with high rates of mortality and long-term disability. Despite a growing interest from the scientific community, currently no decisive therapeutic target has been established. Perihematomal hypoperfusion may lead to ischemic damage during intraparenchymal cerebral hemorrhage (ICH), resulting in worse prognosis. We aimed to (1) investigate the relationship between serum biomarkers related to oxidative stress and vasoactive substances and the occurrence of hypoperfusion and ischemic perihematomal lesions in ICH, and (2) to evaluate their correlation with the volumetric evolution of the hematoma and perihematomal edema. We enrolled 28 patients affected by ICH. Blood samples were collected at three different timepoints from symptoms onset: T0, T1 and T2 (admission, 12-24hs and 48-72hs respectively), to measure Endothelin-1 (ET-1), nitrites/nitrates (NO), NADPH oxidase-2 (NOX-2) and asymmetric dimethylarginine (ADMA). Patients underwent brain MRI with perfusion study at T1 and MRI without perfusion at T2. 12 patients had ischemic perihematomal lesions at T1. A higher NOX-2 concentration at T0 was observed in patients with ischemic perihematomal lesions compared to those without (p=0.051) and with a more severe perihematomal edema at T2 (p=0.011). The ischemic perihematomal lesions development was also associated with increased hematoma volume (p<0.005), perilesional edema (p=0.046), greater midline shift (p=0.036). ET-1 values at T1 inversely correlated with hemorrhage volume at T2 (ρ=-0.717, p=0.030). NOX-2 may have a key role in the development of ischemic perihematomal lesions, aligning with previous research indicating that oxidative stress contributes to secondary brain injury in ICH. The association between higher ET-1 values and a lower hemorrhage volume could be related to the ET-1 vasoconstriction action on the ruptured vessel wall.