Abstract
Reactive oxygen species and their detrimental effects on the brain after transient ischemia/reperfusion (I/R) have been implicated in the pathogenesis of ischemic reperfusion injury. Thioredoxin-1 (Trx-1) is an endogenous antioxidant protein that has neuroprotective effects. We hypothesized that Trx-1 plays a crucial role in regulating cerebral I/R injury. To be able to test this, 190 Sprague–Dawley rats were subjected to transient middle cerebral artery occlusion (tMCAO) with Trx-1 siRNA (small interference RNA) injected 24h prior to ischemia. At 24h after tMCAO, we measured neurological deficits, infarct volume, and brain water content, and found that neurological dysfunction, brain infarct size, and brain edema were worse in the Trx-1 siRNA group than in the control group. Oxidative stress was evaluated by measuring superoxide dismutase activity and malondialdehyde level. The levels of Trx-1 and its cofactor, peroxiredoxin (Prdx), were significantly decreased after Trx-1 down-regulated. However, there is no significant difference in the Prdx mRNA level after administration of Trx-1 siRNA. In contrast, Prdx-SO3 protein levels were significantly increased in the Trx-1 siRNA group. We also investigated the specific role of nuclear factor erythroid 2-related factor 2 (Nrf2) in Trx-1 induction by knocking down Nrf2. Nrf2 siRNA injection decreased Trx-1 mRNA and protein expression. Our results suggest that the exacerbation of brain damage was associated with enhanced cerebral peroxidation in brain tissues. Moreover, these results revealed that Trx-1, which is more likely regulated by Nrf2, exerts a neuroprotective role probably through maintaining the reduction activity of Prdx1–4.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
