The Role of Oxidative Stress in Early Brain Injury after Subarachnoid Hemorrhage

Jelinek, Matyas; Jurajda, Michal; Ďuriš, Kamil

doi:10.1155/2020/8877116

Cited by 10 publications

(10 citation statements)

References 76 publications

(160 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These include acute effects of oxidative stress on early brain injury and effects of hyperoxemia on DCI. 13,23 Following acute brain injury, disruption of cellular respiration results in increased production of ROS that overwhelm the antioxidant systems and contribute to secondary brain injury. 23,24 Indeed, it has been found that even healthy patients exposed to hyperoxia transiently develop increased ROS burden, lipid peroxidation, and reduced nitric oxide metabolites.…”

Section: Discussionmentioning

confidence: 99%

Effects of hyperoxemia on aneurysmal subarachnoid hemorrhage outcomes: a systematic review and meta-analysis

Ahn

Mastorakos

Sokolowski

et al. 2022

Neurosurgical Focus

View full text Add to dashboard Cite

OBJECTIVE In recent years, hyperoxemia in the intensive care unit has received attention as potentially contributing to negative outcomes in the setting of cardiac arrest, ischemic stroke, and traumatic brain injury. The authors sought to evaluate whether hyperoxemia contributes to worse outcomes in the setting of aneurysmal subarachnoid hemorrhage (aSAH) and to summarize suggested pathophysiological mechanisms. METHODS A systematic literature review was conducted without date restrictions on the PubMed and Web of Science databases on September 15, 2021. All studies that assessed the relationship between patients treated for aSAH and hyperoxemia were eligible independent of the criteria used to define hyperoxemia. All nonclinical studies and studies that did not report outcome data specific to patients with aSAH were excluded. A total of 102 records were found and screened, resulting in assessment of 10 full-text studies, of which 7 met eligibility criteria. Risk of bias was assessed using the Downs and Black checklist. A meta-analysis on the pooled 2602 patients was performed, and forest plots were constructed. Additionally, a review of the literature was performed to summarize available data regarding the pathophysiology of hyperoxemia. RESULTS The included studies demonstrated an association between hyperoxemia and increased morbidity and mortality following aSAH. The criteria used to determine hyperoxemia varied among studies. Pooling of univariate data showed hyperoxemia to be associated with poor neurological outcome (OR 2.26, 95% CI 1.66–3.07; p < 0.001), delayed cerebral ischemia (DCI) (OR 1.91, 95% CI 1.31–2.78; p < 0.001), and increased incidence of poor neurological outcome or mortality as a combined endpoint (OR 2.36, 95% CI 1.87–2.97; p < 0.001). Pooling of multivariable effect sizes showed the same relationship for poor neurological outcome (OR 1.28, 95% CI 1.07–1.55; p = 0.01) and poor neurological outcome and mortality as a combined endpoint (OR 1.17, 95% CI 1.11–1.23; p < 0.001). Additionally, review of preclinical studies underlined the contribution of oxidative stress due to hyperoxemia to acute secondary brain injury and DCI. CONCLUSIONS Reported outcomes from the available studies have indicated that hyperoxemia is associated with worse neurological outcome, mortality, and DCI. These findings provide a general guideline toward avoiding hyperoxemia in the acute setting of aSAH. Further studies are needed to determine the optimal ventilation and oxygenation parameters for acute management of this patient population.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of hyperoxemia on aneurysmal subarachnoid hemorrhage outcomes: a systematic review and meta-analysis

Ahn

Mastorakos

Sokolowski

et al. 2022

Neurosurgical Focus

View full text Add to dashboard Cite

show abstract

“…Our data fall in line with previous articles addressing the importance of free radicals in EBI after SAH. Although there are many different sources that contribute to excessive free radical production, it is believed that mitochondrial overproduction and hemoglobin auto-oxidation are the most important [ 23 ]. The leakage of superoxide anions from mitochondria, caused by ischemic disruption of the electron transfer chain, accounts for most of the free radicals in EBI after SAH [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Reestablishment of the membrane potential is achieved by increased substrate oxidation and O 2 consumption, leading to the generation of superoxide [ 18 ]. The resulting excess of free radicals leads to an overload of the antioxidant systems, ultimately causing oxidative stress and the resulting damage to lipids, proteins, and DNA [ 18 , 23 ]. The delayed nature of this phenomenon might explain the time course of differences in TAC levels in the plasma and CSF of patients with SAH.…”

Section: Discussionmentioning

confidence: 99%

“…SAH leads to an increase in Cu-SOD and Zn-SOD activity and the SOD/GSH-Px ratio [ 20 ]. This change in balance between SOD and GSH-Px leads to the accumulation of OH − , subsequent oxidative stress, and consecutive EBI [ 23 ]. In our cohort, we observed an increase in SOD in the plasma and CSF of patients with SAH between days 1 and 7, while GSH-Px levels remained unchanged.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Krenzlin

Wesp

Schmitt

et al. 2021

JCM

View full text Add to dashboard Cite

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, p = 0.99; d7: 1.52 ± 0.4 U/L, p = 0.019) and were significantly higher compared to controls (1.11 ± 0.27 U/L) at day 7 (p < 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, p = 0.10; d7: 2.37 ± 1.29 U/L, p < 0.0001) without becoming significantly different compared to controls (1.74 ± 0.8 U/L, p = 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, p = 0.25). TAC remained unchanged from day 1 to 7 (d3: 92.64 ± 68.58 µmol/L, p = 0.86; d7: 74.07 ± 54.95 µmol/L, p = 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, p = 0.0046; d7: 85.35 ± 103.9 µmol/L, p < 0.0001). Decreased SOD levels in plasma and CSF are associated with a worse neurological outcome 6 weeks (mRS: CSF p = 0.0001; plasma p = 0.027/GOSE: CSF p = 0.001; plasma p = 0.001) and 6 months (mRS: CSF p = 0.001; plasma p = 0.09/GOSE: CSF p = 0.001; plasma p = 0.001) after SAH. Increased plasma TAC correlated with a worse neurological outcome 6 weeks (mRS: p = 0.001/GOSE p = 0.001) and 6 months (mRS p = 0.001/GOSE p = 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.

show abstract

“…Furthermore, treatment of ICH using hydrogen and active hydrogen compounds, targeted therapy against oxidative stress signaling pathways, synthetic antioxidant drugs (Edaravone) and targeted gene therapy have also been used [ 75 ]. Molecules with antioxidant capacity for alleviating oxidative stress were also used in an experimental treatment of subarachnoid hemorrhage [ 80 , 81 ].…”

Section: Antioxidant Treatment Strategies Of Oxidative Stress In Strokementioning

confidence: 99%

Oxidative Stress in the Brain: Basic Concepts and Treatment Strategies in Stroke

2021

Self Cite

View full text Add to dashboard Cite

The production of free radicals is inevitably associated with metabolism and other enzymatic processes. Under physiological conditions, however, free radicals are effectively eliminated by numerous antioxidant mechanisms. Oxidative stress occurs due to an imbalance between the production and elimination of free radicals under pathological conditions. Oxidative stress is also associated with ageing. The brain is prone to oxidative damage because of its high metabolic activity and high vulnerability to ischemic damage. Oxidative stress, thus, plays a major role in the pathophysiology of both acute and chronic pathologies in the brain, such as stroke, traumatic brain injury or neurodegenerative diseases. The goal of this article is to summarize the basic concepts of oxidative stress and its significance in brain pathologies, as well as to discuss treatment strategies for dealing with oxidative stress in stroke.

show abstract

The Role of Oxidative Stress in Early Brain Injury after Subarachnoid Hemorrhage

Cited by 10 publications

References 76 publications

Effects of hyperoxemia on aneurysmal subarachnoid hemorrhage outcomes: a systematic review and meta-analysis

Effects of hyperoxemia on aneurysmal subarachnoid hemorrhage outcomes: a systematic review and meta-analysis

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

Oxidative Stress in the Brain: Basic Concepts and Treatment Strategies in Stroke

Contact Info

Product

Resources

About