Clinical Prognosis for SAH Consistent with Redox Imbalance and Lipid Peroxidation

Abstract

Subarachnoid hemorrhage (SAH) accounts for 3% of all strokes. As more and more data indicates the role of oxidative stress in acute brain damage caused by SAH, an attempt was made to correlate the clinical status of patients with systemic level of antioxidants and lipid peroxidation products. The hemorrhage was diagnosed with brain computed tomography (CT) and aneurysm with angio-CT and angiography, while the vasospasm was monitored with transcranial Doppler. Plasma glutathione peroxidase activity (GSH-Px) and vitamin A, E, and C levels were determined spectrophotometrically and by HPLC, respectively. The levels of polyunsaturated fatty acids (PUFAs) cyclization products were determined by GC-MS, while F 2 -isoprostanes and neuroprostanes (NP) were determined by LC-MS. SAH was accompanied by changes in antioxidant capacity in blood plasma, including initially (day 1) an increase in GSH-Px activity, followed by its decrease and a progressive decrease in glutathione (GSH) levels and vitamins A, E, and C. On the other hand, levels of PUFAs cyclization products, F 2 -isoprostanes, and neuroprostanes were highest on day 1 (two and eight times higher, respectively) and decreased over time. The levels of 4-HNE (4-hydroxynonenal), 4-ONE (4-oxononenal), and MDA (malondialdehyde) changed similarly. In contrast, the 4-HHE (4-hydroxyhexenal) level reduced after SAH increased significantly after a week. It was found that the deterioration of the overall clinical and neurological condition of SAH patients due to cerebral edema, intracranial hemorrhage, or vasoconstriction corresponded to reduced antioxidant defense and, as a consequence, increased lipid peroxidation and slower observed changes in regression. It can be concluded that monitoring the level of lipid peroxidation products (neuroprostanes, 4-ONE, and MDA) can support the monitoring of the clinical status of patients, especially with regard to the assessment of vasospasm.

Mechanisms of Oxidative Stress and Therapeutic Targets following Intracerebral Hemorrhage

“…4-HNE levels in cerebrospinal fluid (CSF) and plasma samples of patients with Parkinson's disease have also been determined by GC-negative-ion chemical ionization mass spectrometry-based detection of O-pentafluorobenzyl oxime [ 60 ]. Vasospasm in patients with SAH has been evaluated based on measurement of lipid peroxidation; the levels of polyunsaturated fatty acid cyclization products, F2-isoprostanes (F2-IsoPs), and neuroprostanes were highest on day 1 post-SAH and decreased over time, with similar trends observed in the levels of 4-HNE, 4-oxononenal, and MDA [ 61 ].…”

Edaravone Dexborneol Treatment Attenuates Neuronal Apoptosis and Improves Neurological Function by Suppressing 4-HNE-Associated Oxidative Stress After Subarachnoid Hemorrhage

“…Oxidative stress has been identified as an important mechanism by which acute brain damage causes neurological dysfunction after SAH ( Jarocka-Karpowicz et al, 2020 ; Wei et al, 2020 ). In addition, neuronal apoptosis has been shown to occur in the brain cortex and hippocampus which are associated with oxidative stress injury following SAH ( Ayer and Zhang, 2008 ).…”

“…Under physiological conditions, redox homeostasis is the result of a balance between the expression of oxidative stress products and the antioxidant capacity. Oxidative stress injury occurs when the production of free radical moieties and lipid peroxides exceeds the antioxidant capacity of the related brain regions ( Fumoto et al, 2019 ; Jarocka-Karpowicz et al, 2020 ). Oxidative stress plays an important role in the course of various pathological changes in early brain injury after SAH, whereas pharmacological or genetic suppression of oxidative stress has been regarded to alleviate early brain injury which is involved in the development of cerebral ischemia and poor outcome ( Fumoto et al, 2019 ).…”

“…Our study shows that both edaravone dexborneol and edaravone treatment display powerful antioxidant functions according to a total antioxidant capability assay with a rapid ABTS method, and the antioxidant ability of edaravone dexborneol is much stronger than that of edaravone alone. In addition, compared to edaravone, edaravone dexborneol treatment shows a stronger ability to suppress the production of MDA, which may be related to DNA damage after SAH as an important product of lipid peroxide ( Zhuang et al, 2019 ; Jarocka-Karpowicz et al, 2020 ).…”

An Update on Antioxidative Stress Therapy Research for Early Brain Injury After Subarachnoid Hemorrhage

“…Hydrogen peroxide (H 2 O 2 ) and the O 2 •– are pivotal agents produced by greater than 40 enzymes ( Murphy, 2009 ; Go et al, 2015 ). Additionally, many other reactive categories are contained in redox signaling, for example, hydrogen sulfide and oxidized lipids ( Fujii et al, 2010 ; Yu et al, 2014 ; Jarocka-Karpowicz et al, 2020 ).…”