Decreased Superoxide Dismutase Concentrations (SOD) in Plasma and CSF and Increased Circulating Total Antioxidant Capacity (TAC) Are Associated with Unfavorable Neurological Outcome after Aneurysmal Subarachnoid Hemorrhage

• Main Authors: Harald Krenzlin, Dominik Wesp, Jan Schmitt, Christina Frenz, Elena Kurz, Julia Masomi-Bornwasser, Johannes Lotz, Florian Ringel, Thomas Kerz, Naureen Keric
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Journal of Clinical Medicine
• Subjects: SAH; CSF; plasma; oxidative stress; ROS; antioxidant capacity
• Online Access: https://www.mdpi.com/2077-0383/10/6/1188

Background: Subarachnoid hemorrhage (SAH) is a devastating disease with high morbidity and mortality. Hypoxia-induced changes and hemoglobin accumulation within the subarachnoid space are thought to lead to oxidative stress, early brain injury, and delayed vasospasm. This study aimed to evaluate the antioxidant status and its impact on neurological outcome in patients with aneurysmal SAH. Methods: In this prospective observational study, 29 patients with aneurysmal SAH were included (mean age 54.7 ± 12.4). Blood and cerebrospinal fluid (CSF) samples were collected on days (d) 1, 3, and 7. In addition, 29 patients without intracranial hemorrhage served as controls. The antioxidant system was analyzed by glutathione peroxidase (GSH-Px; U/L) and total and free glutathione-sulfhydryl (GSH; mg/L) in the plasma. Superoxide dismutase (SOD, U/mL) and total antioxidant capacity (TAC, µmol/L) were measured in the serum and CSF. Clinical data were compiled on admission (Hunt and Hess grade, Fisher grade, and GCS). Neurological and cognitive outcome (modified Rankin scale (mRS), Glasgow Outcome Scale Extended (GOSE) and Montreal Cognitive Assessment (MoCA)) was assessed after 6 weeks (6 w) and 6 months (6 m). Results: Plasma levels of SOD increased from day 1 to 7 after SAH (d1: 1.22 ± 0.36 U/L; d3: 1.25 ± 0.33 U/L, <i>p</i> = 0.99; d7: 1.52 ± 0.4 U/L, <i>p</i> = 0.019) and were significantly higher compared to controls (1.11 ± 0.27 U/L) at day 7 (<i>p</i> < 0.001). Concordantly, CSF levels of SOD increased from day 1 to 7 after SAH (d1: 1.22 ± 0.41 U/L; d3: 1.77 ± 0.73 U/L, <i>p</i> = 0.10; d7: 2.37 ± 1.29 U/L, <i>p</i> < 0.0001) without becoming significantly different compared to controls (1.74 ± 0.8 U/L, <i>p</i> = 0.09). Mean plasma TAC at day 1 (d1: 77.87 ± 49.72 µmol/L) was not statistically different compared to controls (46.74 ± 32.42 µmol/L, <i>p</i> = 0.25). TAC remained unchanged from day 1 to 7 (d3: 92.64 ± 68.58 µmol/L, <i>p</i> = 0.86; d7: 74.07 ± 54.95 µmol/L, <i>p</i> = 0.8) in plasma. TAC in CSF steeply declined from day 1 to 7 in patients with SAH becoming significantly different from controls at days 3 and 7 (d3: 177.3 ± 108.7 µmol/L, <i>p</i> = 0.0046; d7: 85.35 ± 103.9 µmol/L, <i>p</i> < 0.0001). Decreased SOD levels in plasma and CSF are associated with a worse neurological outcome 6 weeks (mRS: CSF <i>p</i> = 0.0001; plasma <i>p</i> = 0.027/GOSE: CSF <i>p</i> = 0.001; plasma <i>p</i> = 0.001) and 6 months (mRS: CSF <i>p</i> = 0.001; plasma <i>p</i> = 0.09/GOSE: CSF <i>p</i> = 0.001; plasma <i>p</i> = 0.001) after SAH. Increased plasma TAC correlated with a worse neurological outcome 6 weeks (mRS: <i>p</i> = 0.001/GOSE <i>p</i> = 0.001) and 6 months (mRS <i>p</i> = 0.001/GOSE <i>p</i> = 0.001) after SAH. Conclusion: In our study, a reduction in the antioxidative enzyme SOD and elevated TAC were associated with a poorer neurological outcome reflected by mRS and GOSE at 6 weeks and 6 months after SAH. A lower initial SOD CSF concentration was associated with the late deterioration of cognitive ability. These findings support the mounting evidence of the role of oxidative stress in early brain injury formation and unfavorable outcome after SAH.