PRDX1 enhances cerebral ischemia-reperfusion injury through activation of TLR4-regulated inflammation and apoptosis.

Stroke is still a leading cause of death across the world. Despite various signals or molecules that contribute to the pathophysiological process have been investigated, the exact molecular mechanisms revealing stroke damage still remain to be explored. Peroxiredoxin 1 (PRDX1) has been identified as a stress-induced macrophage redox protein with multiple functions. Although PRDX1 is a critical factor related to the regulation of immunity, inflammation, apoptosis and oxidative stress, its effects on cerebral ischemia-reperfusion (I-R) injury were presently unclear. In the study, by using a mouse model of I-R injury, we found that PRDX1 expression was up-regulated during I-R injury in a time-dependent manner. Additionally, PRDX1-knockout mice showed reduced infarction area and alleviated neuropathological scores with decreased brain water contents. Furthermore, cell death and inflammatory response in mice with cerebral I-R injury were markedly attenuated by PRDX1 knockout, which were associated with the blockage of Caspase-3 and nuclear factor-κB (NF-κB) signaling pathways. Mechanistically, PRDX1-regulated cerebral I-R injury was through the promotion of toll-like receptor-4 (TLR4), as proved by the evidence that TLR4 suppression abrogated the exacerbated effect of TLR4 on inflammatory response and apoptosis in oxygen and glucose deprivation (OGD)-treated primary microglial cells. These data demonstrated that PRDX1 contributed to cerebral stroke by interacting with TLR4, providing an effective therapeutic approach for cerebral I-R injury.