Stroke is one of the leading causes of death and disability in the world. Oxidative stress, which refers to an excessive generation of reactive oxygen species (ROS), plays a key role in the pathological process of stroke. Excessive ROS production contributes to brain ischemia/reperfusion injury through many mechanisms including BBB disruption, inflammation, apoptosis, and cellular necrosis. Nuclear factor-E2-related factor 2 (Nrf2) is one of the critical regulators of endogenous antioxidant defense, which promote the transcription of a wide variety of antioxidant genes. Emerging evidence has demonstrated that activation of Nrf2 and its target genes may protect the brain against ischemia/reperfusion injury, and therapies aimed at increasing Nrf2 activity appear to be beneficial to alleviate brain injury in stroke through the suppression of oxidative stress. The main purpose of this review is to discuss the current evidence for the role of Nrf2 in stroke and the potential interventions to enhance Nrf2 activation to attenuate stroke-induced injury.

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In response to stroke, astrocytes become reactive astrogliosis and are a major component of a glial scar. This results in the formation of both a physical and chemical (production of chondroitin sulfate proteoglycans) barrier, which prevent neurite regeneration that, in turn, interferes with functional recovery. However, the mechanisms of reactive astrogliosis and glial scar formation are poorly understood. In this work, we hypothesized that repulsive guidance molecule a (RGMa) regulate reactive astrogliosis and glial scar formation. We first found that RGMa was strongly expressed by reactive astrocytes in the glial scar in a rat model of middle cerebral artery occlusion/reperfusion. Genetic or pharmacologic inhibition of RGMa in vivo resulted in a strong reduction of reactive astrogliosis and glial scarring as well as in a pronounced improvement in functional recovery. Furthermore, we showed that transforming growth factor β1 (TGFβ1) stimulated RGMa expression through TGFβ1 receptor activin-like kinase 5 (ALK5) in primary cultured astrocytes. Knockdown of RGMa abrogated key steps of reactive astrogliosis and glial scar formation induced by TGFβ1, including cellular hypertrophy, glial fibrillary acidic protein upregulation, cell migration, and CSPGs secretion. Finally, we demonstrated that RGMa co-immunoprecipitated with ALK5 and Smad2/3. TGFβ1-induced ALK5-Smad2/3 interaction and subsequent phosphorylation of Smad2/3 were impaired by RGMa knockdown. Taken together, we identified that after stroke, RGMa promotes reactive astrogliosis and glial scar formation by forming a complex with ALK5 and Smad2/3 to promote ALK5-Smad2/3 interaction to facilitate TGFβ1/Smad2/3 signaling, thereby inhibiting neurological functional recovery. RGMa may be a new therapeutic target for stroke.

Aim: Oxidative stress and inflammation play critical roles in the neuropathogenesis of PD. We aimed to evaluate oxidative stress and inflammation status by measuring serum superoxide dismutase (SOD) with lipoprotein cholesterol and high-sensitivity C-reactive protein (hsCRP) respectively in PD patients, and explore their correlation with the disease severity. Methods: We performed a cross-sectional study that included 204 PD patients and 204 age-matched healthy controls (HCs). Plasma levels of SOD, hsCRP, total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. A series of neuropsychological assessments were performed to rate the severity of PD. Results: The plasma levels of SOD (135.7 ± 20.14 vs. 147.2 ± 24.34, P < 0.0001), total cholesterol, HDL-C and LDL-C in PD were significantly lower than those in HCs; the hsCRP level was remarkably increased in PD compared to HC (2.766 ± 3.242 vs. 1.637 ± 1.597, P < 0.0001). The plasma SOD was negatively correlated with the hsCRP, while positively correlated with total cholesterol, HDL-C, and LDL-C in PD patients. The plasma SOD were negatively correlated with H&Y, total UPDRS, UPDRS (I), UPDRS (II), and UPDRS (III) scores, but positively correlated with MoCA and MMSE scores. Besides,