Abstract
Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by high mortality and disability rates. To date, the exact etiology of ICH-induced brain injury is still unclear. Moreover, there is no effective treatment to delay or prevent disease progression currently. Increasing evidence suggests that ferroptosis plays a dominant role in the pathogenesis of ICH injury. Baicalin is a main active ingredient of Chinese herbal medicine Scutellaria baicalensis. It has been reported to exhibit neuroprotective effects against ICH-induced brain injury as well as reduce iron deposition in multiple tissues. Therefore, in this study, we focused on the protective mechanisms of baicalin against ferroptosis caused by ICH using a hemin-induced in vitro model and a Type IV collagenase-induced in vivo model. Our results revealed that baicalin enhanced cell viability and suppressed ferroptosis in rat pheochromocytoma PC12 cells treated with hemin, erastin and RSL3. Importantly, baicalin showed anti-ferroptosis effect on primary cortical neurons (PCN). Furthermore, baicalin alleviated motor deficits and brain injury in ICH model mice through inhibiting ferroptosis. Additionally, baicalin existed no obvious toxicity towards the liver and kidney of mice. Evidently, ferroptosis is a key pathological feature of ICH and baicalin can prevent the development of ferroptosis in ICH. As such, baicalin is a potential therapeutic drug for ICH treatment.
Highlights
Intracerebral hemorrhage (ICH) is a common type of stroke characterized by high mortality and disability rates (Lim et al, 2020)
glutathione peroxidase 4 (GPX4) and solute carrier family 7 membrane 11 (SLC7A11) levels were further detected using immunofluorescence staining to confirm the protective effect of baicalin against ferroptosis in hemin-treated PC12 cells
The GPX4 depletion induced by hemin lead to a compensatory increase of upstream protective regulator SLC7A11 expression, while baicalin treatment effectively enhanced the expression of SLC7A11 (Figures 2F,G)
Summary
Intracerebral hemorrhage (ICH) is a common type of stroke characterized by high mortality and disability rates (Lim et al, 2020). ICH causes brain injury by primary physical disruption of the cellular architecture and secondary brain injuries such as edema, toxicity from metabolites of hemoglobin degradation and cell death (Duan et al, 2016; An et al, 2017). Surgical evacuation of hematoma is the primary treatment of ICH. It has many limitations and may lead to secondary injuries (de Oliveira Manoel, 2020). The exact cause of ICH-induced brain injury is still unclear, increasing evidence suggests that the disorder of iron metabolism plays an important role in the pathogenesis of ICH injury (Wan et al, 2019)
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