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

Abstract

The main reasons for disability and death in aneurysmal subarachnoid hemorrhage (aSAH) may be early brain injury (EBI) and delayed cerebral ischemia (DCI). Despite studies reporting and progressing when DCI is well-treated clinically, the prognosis is not well-improved. According to the present situation, we regard EBI as the main target of future studies, and one of the key phenotype-oxidative stresses may be called for attention in EBI after laboratory subarachnoid hemorrhage (SAH). We summarized the research progress and updated the literature that has been published about the relationship between experimental and clinical SAH-induced EBI and oxidative stress (OS) in PubMed from January 2016 to June 2021. Many signaling pathways are related to the mechanism of OS in EBI after SAH. Several antioxidative stress drugs were studied and showed a protective response against EBI after SAH. The systematical study of antioxidative stress in EBI after laboratory and clinical SAH may supply us with new therapies about SAH.

Efficacy of Resveratrol in Experimental Subarachnoid Hemorrhage Animal Models: A Stratified Meta-Analysis

“…Too few studies might lead to an overestimation of the efficacy of RES. Besides, many studies suggested that 24 h after SAH is the optimum time point to complete the pathological and functional detection of EBI in animals ( Lin et al, 2021 ). Therefore, normalizing the selection of the observation point needs to be performed in future studies.…”

Progress in Research on TLR4-Mediated Inflammatory Response Mechanisms in Brain Injury after Subarachnoid Hemorrhage

“…Therefore, researchers began to pay attention to the new mechanism of nerve injury caused by SAH. Currently, the research on the mechanism of poor clinical prognoses caused by SAH mainly focuses on early brain injury (EBI) and delayed brain injury (DBI) [ 34 , 35 ]. In particular, EBI is considered to be the main reason for the poor outcomes in patients after SAH [ 34 , 36 , 37 ].…”

“…Post-SAH EBI refers to any acute pathophysiological events that occur in the brain within 72 h after SAH, such as brain cell death, blood–brain barrier destruction, cerebral edema, oxidative stress, neurological deficits, acute vasospasm and impaired brain autoregulation [ 34 , 38 ]. In contrast to EBI, DBI refers to the pathophysiological event in brain tissue 72 h after SAH, which is mainly caused by delayed cerebral vasospasm (DCV) [ 39 , 40 ].…”

Activation of SIRT1 Alleviates Ferroptosis in the Early Brain Injury after Subarachnoid Hemorrhage

“…Redox homeostasis regulates the normal physiological functions of cells. Excessive free radicals can exhaust the intrinsic antioxidant system, resulting in lipid peroxidation, DNA damage, and protein breakdown [ 11 ]. Ferroptosis is a new regulated cell death induced by excessive free radicals [ 12 ].…”

“…Sirtuin 1 (SIRT1) is a well-known epigenetic regulator that modulates gene transcription and impacts various biological functions, such as oxidative stress, inflammatory response, and mitochondrial biogenesis [26]. Numerous studies have shown that SIRT1 has a great antioxidative capacity and plays a neuroprotective role against EBI after SAH [11]. SIRT1 activation mitigates the oxidative stressinduced EBI by inhibiting p53-and nuclear factor-kappa B-(NF-κB-) mediated oxidative pathways and upregulating the nuclear factor-erythroid 2-related factor 2 antioxidant pathway [27][28][29].…”