Srs11‐92, a ferrostatin‐1 analog, improves oxidative stress and neuroinflammation via Nrf2 signal following cerebral ischemia/reperfusion injury

Abstract

Aim Ferroptosis is increasingly becoming to be considered as an important mechanism of pathological cell death during stroke, and specific exogenous ferroptosis inhibitors have the ability to reverse cerebral ischemia/reperfusion injury. However, research on Srs11‐92 (AA9), a ferrostatin‐1 (Fer‐1) analog, in preclinical studies is limited. Methods In the middle cerebral artery occlusion‐reperfusion (MCAO/R) mice model or oxygen–glucose deprivation/reperfusion (OGD/R) cell model, Fer‐1, AA9, and/or ML385 were administered, and brain infarct size, neurological deficits, neuronal damage, oxidative stress, and neuroinflammation were determined after the damage, in vitro and in vivo. Results Fer‐1 and AA9 improved brain infarct size, neuronal damage, and neurological deficits in mice model of MCAO/R, and inhibited the overloaded iron deposition, ROS accumulation, and neuroinflammation response: it also increased the expression of GPx4, Nrf2, and HO‐1 and suppressed the expression of HMGB1 and NF‐κB p65 in the epicenter of injured hippocampal formation. However, Nrf2 inhibitor ML385 reversed the neuroprotective effect of AA9, including the oxidative stress and neuroinflammation. In vitro studies showed that AA9 relieved OGD/R‐induced neuronal oxidative stress and neuroinflammation via the Nrf2 pathway, which was impaired by ML385 in primary neurons. Conclusion The findings imply that Fer‐1 analog AA9 may be suitable for further translational studies for the protection of neuronal damage via Nrf2 signal pathway‐mediated oxidative stress and neuroinflammation in stroke and others neurological diseases.

Akkermansia muciniphila-Nlrp3 is involved in the neuroprotection of phosphoglycerate mutase 5 deficiency in traumatic brain injury mice

“…The academic community has been devoted to exploring various neuroprotective strategies after neuronal injury ( 29 – 31 ). In present work, we found significant differences in gut microbiota composition (including a high level of A. muciniphila ) in male Pgam5 -/- mice compared to male WT mice.…”

Exogenous Functional Mitochondria Derived from Bone Mesenchymal Stem Cells That Respond to ROS Can Rescue Neural Cells Following Ischemic Stroke

“…In addition, the inflammatory response after cerebral infarction can exacerbate oxidative stress. 28–30 The inflammatory response will lead to the infiltration and chemotaxis of a large number of inflammatory cells, which will release a large amount of reactive oxygen species and inflammatory factors, further aggravating cell damage and death. We found that the increase in SDH and ROS immunoreactivity in microglial cells after MCAO compared to the control samples was reversed by treatment with F-Mito.…”

Remimazolam Attenuates LPS-Derived Cognitive Dysfunction via Subdiaphragmatic Vagus Nerve Target α7nAChR-Mediated Nrf2/HO-1 Signal Pathway

“…The sepsis rat model was established via intraperitoneal injection of 5 mg/kg LPS [ 12 ], followed by intravenous injection of remimazolam (10 mg/kg; Jiangsu; China) [ 8 ] or 0.9% saline. Notably, α7nAChR agonist (PNU282987, 10 mg/kg, Sigma, USA) [ 13 ], Nrf2/HO-1 inhibitor (ML385, 30 mg/kg, Selleck, USA) [ 14 ], and α7nAChR antagonist (MLA, 3 mg/kg, abcam) [ 15 ] were dissolved in normal saline with 2% DMSO and administered intraperitoneally 30 min before LPS treatment. The SDV or Sham rats underwent surgery two weeks before modeling.…”