Mechanisms of Oxidative Stress and Therapeutic Targets following Intracerebral Hemorrhage

Yao, Zhenjia; Bai, Qinqin; Wang, Gaiqing

doi:10.1155/2021/8815441

Cited by 65 publications

(44 citation statements)

References 112 publications

(164 reference statements)

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“…Oxidative stress is one of the main causes of brain injury after ICH. It participates in various important pathophysiological processes after ICH (7). Oxidative stress causes BBB injury, irreversible damage to neurovascular structures, serious brain edema and brain cell death (5,34).…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress refers to the excessive production of free radicals, which mainly include reactive oxygen species (ROS). In addition, ICH-induced inflammation induces the production of many free radicals, which lead to cell damage (1,7). Therefore, antioxidant therapy is regarded as a valuable and hopeful direction for the treatment of ICH.…”

Section: Introductionmentioning

confidence: 99%

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BMAL1 attenuates intracerebral hemorrhage-induced secondary brain injury in rats by regulating the Nrf2 signaling pathway

Gong¹,

Zhang²,

Li³

et al. 2021

Ann Transl Med

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Background: Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with high morbidity and mortality rates. Oxidative stress and inflammation are important pathological mechanisms of secondary brain injury (SBI) after ICH. Brain and muscle Arnt-like protein 1 (BMAL1), which forms the core component of the circadian clock, was previously shown to be involved in many diseases and to participate in oxidative stress and inflammatory responses. However, the role of BMAL1 in SBI following ICH is unknown. In addition, treatments targeting miR-155 and its downstream signaling pathway may exert a beneficial effect on SBI after ICH, while miR-155 may regulate Bmal1 mRNA stability and translation. Nevertheless, researchers have not clearly determined whetheantagomir-155 upregulates BMAL1 expression and subsequently attenuates ICHinduced brain injury in rats.Methods: After establishing an ICH rat model by injecting autologous blood, the time course of changes in levels of the BMAL1 protein after ICH was analyzed. Subsequently, this study was designed to investigate the potential role and mechanisms of BMAL1 in SBI following ICH using lentiviral overexpression and antagomir-155 treatments.Results: BMAL1 protein levels were significantly decreased in the ICH group compared to the sham group. Genetic overexpression of BMAL1 alleviated oxidative stress, inflammation, brain edema, bloodbrain barrier injury, neuronal death, and neurological dysfunction induced by ICH. On the other hand, we observed that inhibiting miRNA-155 using antagomir-155 promoted the expression of BMAL1 and further activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway to attenuate brain injury after ICH.Conclusions: These results reveal that BMAL1 serves as a neuroprotective agent in ICH and upregulation of BMAL1 attenuates ICH-induced SBI. Therefore, BMAL1 may be a promising therapeutic target for SBI following ICH.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

BMAL1 attenuates intracerebral hemorrhage-induced secondary brain injury in rats by regulating the Nrf2 signaling pathway

Gong¹,

Zhang²,

Li³

et al. 2021

Ann Transl Med

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show abstract

“…Oxidative stress is caused by the accumulation of ROS after ICH and leads to secondary damage to the brain tissue [27]. Next, the expression of ROS in brain tissues, and oxidative stress markers in serum of rats were determined.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Baicalein in Brain Injury After Intracerebral Hemorrhage by Inhibiting the ROS/NLRP3 Inflammasome Pathway

et al. 2021

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Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high disability/mortality. Baicalein has strong anti-in ammatory activity. This study aims to explore the mechanism of baicalein on brain injury after ICH. The model of brain injury after ICH was established by collagenase induction, followed by the evaluation of neurological severity, brain water content, the degenerated neurons, neuronal apoptosis and reactive oxygen species (ROS). The ICH model was treated with baicalein and silencing NLRP3 to detect brain injury. The expression of NLRP3 in ammasome was detected after treatment with ROS scavenger. The expression of oxidative stress markers and in ammatory factors were detected, and the levels of components in NLRP3 in ammasome were detected. Baicalein reduced the damage of nervous system, lesion surface, brain water content and apoptosis. Baicalein inhibited malondialdehyde and increased IL-10 by inhibiting ROS in brain tissue after ICH. Baicalein inhibited the high expression of NLRP3 in ammasome in ICH. ROS scavenger inhibited the NLRP3 in ammatory response by inhibiting ROS levels. Silencing NLRP3 alleviated the brain injury after ICH by inhibiting excessive oxidative stress and in ammatory factors. Overall, baicalein alleviated the brain injury after ICH by inhibiting ROS and NLRP3 in ammasome.

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“…Secondly, serum UA has pro-oxidant properties by increasing the production of reactive oxygen species (ROS). 26 Then, the increased oxidative stress level can aggravate secondary brain injury after ICH through inflammatory response, apoptosis, autophagy and destruction of blood–brain barrier, 27 and eventually contribute to END. Last but not the least, individuals with higher levels of UA were more likely to have larger baseline hematoma volume, higher proportions of intraventricular hemorrhage and hematoma expansion, and all of which have been shown to be risk factors associated with END in patients with ICH.…”

Section: Discussionmentioning

confidence: 99%

High Uric Acid Level Predicts Early Neurological Deterioration in Intracerebral Hemorrhage

Xiao¹,

Lu²,

Feng³

et al. 2021

NDT

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Objective Increased level of serum uric acid (UA) is often considered a risk factor for ischemic stroke. However, there are limited data on the association between UA and intracerebral hemorrhage (ICH). This study aimed to examine the connection between UA and early neurological deterioration (END) in patients with ICH. Methods This is a prospective observational study. Patients with ICH were enrolled from January 2017 to December 2020. END was diagnosed as the Canadian Stroke Scale (CSS) score decreased ≥1 points between admission and 48 hours. UA was measured at admission. Multivariable logistic regression analysis was performed to explore the relationship between serum UA and END. Results Of the 498 enrolled patients, 132 (26.5%) were developed with END. Patients with END had a significantly higher level of serum UA (332 vs 270 µmol/L, P < 0.001). Univariate logistic regression analysis indicated that patients with the highest quartile of UA level had an OR of 3.256 (95% CI: 1.849–5.734, P < 0.001) for END compared with those with the lowest quartile of UA level. After adjusting for major confounders, the highest UA quartile remained as an independent predictor for END (OR = 2.282, 95% CI: 1.112–4.685, P = 0.013). Conclusion Higher serum UA level was independently associated with END in patients with ICH; therefore, intervention to lower UA level may be worth considering.

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Mechanisms of Oxidative Stress and Therapeutic Targets following Intracerebral Hemorrhage

Cited by 65 publications

References 112 publications

BMAL1 attenuates intracerebral hemorrhage-induced secondary brain injury in rats by regulating the Nrf2 signaling pathway

BMAL1 attenuates intracerebral hemorrhage-induced secondary brain injury in rats by regulating the Nrf2 signaling pathway

Mechanism of Baicalein in Brain Injury After Intracerebral Hemorrhage by Inhibiting the ROS/NLRP3 Inflammasome Pathway

High Uric Acid Level Predicts Early Neurological Deterioration in Intracerebral Hemorrhage

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