Oxidative stress (OS) is induced by the accumulation of reactive oxygen species (ROS) following intracerebral hemorrhage (ICH) and plays an important role in secondary brain injury caused by the inflammatory response, apoptosis, autophagy, and blood-brain barrier (BBB) disruption. This review summarizes the current state of knowledge regarding the pathogenic mechanisms of brain injury after ICH, markers for detecting OS, and therapeutic strategies that target OS to mitigate brain injury.
Background: Hematoma is the chief culprit in brain injury following intracranial cerebral hemorrhage (ICH). Noninvasive hematoma clearance could be an option to prevent and alleviate early brain injury after ICH. Peroxisome proliferator-activated receptor γ (PPAR-γ) and nuclear factor-erythroid 2 related factor-2 (Nrf2) facilitate removal of hematoma in ICH. Monascin acts as the natural Nrf2 activator with PPAR-γ agonist, and the long-term effects of monascin following ICH have not been elucidated. Methods: ICH in rats was induced by stereotactic, intrastriatal injection of type IV collagenase. Monascin was administered twice daily by gastric perfusion for 14 days after ICH induction. Long-term neurological scores (T maze, Garcia scales, rotor rod test, and Morris water maze), hematoma volume, as well as iron overload around hematoma and brain atrophy were evaluated at 7, 14, and 28 days after ICH. Results: The results showed that monascin improved long-term neurological deficits, spatial memory performance, learning ability, and brain shrinkage after ICH. Monascin also reduced hematoma volume at 7 days and iron content at 7 and 14 days after ICH. Conclusion: PPAR γ and Nrf2 play a crucial role in hematoma clearance after ICH in rat. As a dual agonist of PPAR γ and Nrf2, monascin improved long-term outcomes by facilitating hematoma clearance, and by attenuating iron overload and brain atrophy after experimental ICH.
Background To explore the effect of microglial functional transformation in hematoma clearance following intracerebral hemorrhage (ICH), and investigate whether Nuclear factor erythroid 2-related factor 2 (Nrf2) -mediated microglial phagocytosis and inflammatory response is beneficial for hematoma clearance and functional recovery in vitro and in vivo experiments after ICH. Methods In vitro experiments, BV-2 cells were cultured and randomly divided into 4 groups: normal control, microglia + Nrf2-siRNA (100 nmol/L), microglia + monascin (15 µM), microglia + Xuezhikang (200 µg/mL). In vivo experiments, 42 mice were divided into sham, ICH+vehicle, ICH+Nrf2-/-, ICH+monascin (10mg/kg/day, twice) and ICH+Xuezhikang (0.2g/kg/day, twice). Neurologic scores, hemoglobin levels, microglial phagocytosis, brain expression of CD80 /Trem1/TNF-α (pro-inflammatory cytokines) as well as CD206/Trem2/BDNF (anti-inflammatory cytokines) were analyzed at 72 hours after surgery. Results The results showed that Nrf2 agonists improved neurological deficits and decreased hemoglobin levels after ICH. The administration of Nrf2 agonist- monascin/ Xuezhikang enhanced microglia-mediated phagocytosis of erythrocytes and bioparticles by up-regulating Nrf2. Alternatively, monascin/Xuezhikang promoted the expressions of Triggering receptor II expressed on myeloid cells (Trem2), CD206 and BDNF, while inhibited the expressions of Trem1,CD80 and TNF-αexpressed in microglia. Conversely, Nrf2 inhibition (Nrf2 siRNA or Nrf2-/-) showed the opposite results following ICH. Conclusions Microglial functional transformation are involved in hematoma clearance following ICH. Nrf2 activation contributes to microglial functional transformation and phagocytic responses then exerts its neuroprotection after ICH. Nrf2 activator (Monascin/Xuezhikang) enhances hematoma clearance and alleviates neuroinflammation via the regulation of microglial functional alteration following ICH.
Background: Activated microglia is essential for hematoma clearance and recovery after intracerebral hemorrhage (ICH). This study aims to evaluate the effect of microglial functional transformation in hematoma clearance after ICH. Through in vitro and in vivo experiments, we also investigate whether Nuclear factor erythroid 2-related factor 2 (Nrf2) -mediated microglial phagocytosis and inflammatory response plays a role in hematoma clearance and functional recovery after ICH.Methods: For in vitro experiments, BV-2 cells were cultured and randomly divided into 4 groups, including normal control, microglia + Nrf2-siRNA (100 nmol/L), microglia + monascin (15 µM), and microglia + Xuezhikang (200 µg/mL) groups. For vivo experiments, 42 mice were divided into2 groups, i.e., sham, ICH+vehicle, ICH+Nrf2-/-, ICH+monascin (10mg/kg/day, twice) and ICH+Xuezhikang (0.2g/kg/day, twice) groups. Further, neurologic scores, hemoglobin levels, microglial phagocytosis, brain expression of CD80/Trem1/TNF-α (pro-inflammatory cytokines),and CD206/Trem2/BDNF(anti-inflammatory cytokines) were analyzed 72 hours after surgery. Results: The results showed that Nrf2 agonists improved neurological deficits and decreased hemoglobin levels after ICH through regulating microglial functional transformation. Administration of Nrf2 agonist- monascin/ Xuezhikang improved microglia-mediated phagocytosis of erythrocytes and bio-particles through Nrf2 upregulation. Alternatively, monascin/ Xuezhikang promoted the expression of Triggering receptor II expressed on myeloid cells(Trem2), CD206, and BDNF while inhibiting the expression of Trem1,CD80, and TNF-α in microglia. Conversely, Nrf2 inhibition (Nrf2 siRNA or Nrf2-/-) demonstrated conflicting results after ICH.Conclusion: Microglial functional transformations are implicated in hematoma clearance after ICH. Nrf2 activation leads to microglial functional transformation and phagocytic responses then exert its neuroprotection after ICH. Nrf2 activator (Monascin /Xuezhikang) improves hematoma clearance and alleviates neuroinflammation by regulating microglial functional alteration after ICH.
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