Tim-3 cell signaling and iNOS are involved in the protective effects of ischemic postconditioning against focal ischemia in rats

Abstract

The protective effect of ischemic postconditioning (IPostC) against stroke has been well-established, and the underlying mechanisms are known to involve inhibited-inflammation and free radical production. Nevertheless, how IPostC affects protein expression of iNOS, nitrotyrosine, and COX-2 has not been characterized. In addition, the role of the galectin-9/Tim-3 cell signaling pathway—a novel inflammatory pathway—in IPostC has not been studied. We examined whether iNOS, nitrotyrosine, and COX-2, as well as galectin-9/Tim-3 are involved in the protective effects of IpostC in a rat focal ischemia model. Western blot and confocal immunofluoresent staining results indicate that IPostC significantly inhibited Tim-3 expression, and that galectin-9 expression was also inhibited. In addition, IPostC attenuated production of iNOS and nitrotyrosine, but not COX-2, suggesting that IPostC has distinct effects on these inflammatory factors. Furthermore, the inflammation inhibitor minocycline blocked Tim-3 and iNOS expression induced by stroke. Taken together, we show that the galectin-9/Tim-3 cell signaling pathway is involved in inflammation induced by stroke, and IPostC may reduce infarction by attenuating this novel pathway as well as the inflammatory factors iNOS and nitrotyrosine, but not COX-2.

Immediate Remote Ischemic Postconditioning Reduces Brain Nitrotyrosine Formation in a Piglet Asphyxia Model

“…This reduction may be a result of an overall increase in eNOS, as well as reduction of iNOS expression across all assessed brain regions. This RIPostC-mediated reduction in nitrosative stress has also been observed in other in vivo and clinical studies [ 28 , 51 , 55 ]. Interestingly, we have also shown significant increase in astroglial and microglia activation not previously observed.…”

“…Similarly, iNOS-knockout mice do not exhibit ischemia-induced iNOS expression and have smaller tissue infarction than wild-type mice after MCA occlusion [ 50 ]. Additionally, a study by Wei and colleagues has shown that ischemic postconditioning attenuated iNOS and nitrotyrosine production following focal MCA occlusion [ 51 ]. Patients with acute myocardial infarct who underwent ischemic postconditioning demonstrated reduction in iNOS activity in white blood cells as well as decreased plasma nitrotyrosine.…”

Regulation of Hypertension for Secondary Prevention of Stroke: The Possible ‘Bridging Function' of Acupuncture

“…EA at ST36 and Extra 37 in SIHRs reduced the BP and elevated the iNOS levels in the RVLM [30]. Inhibition of iNOS expression decreases the release of glutamate and ameliorates the stroke outcome [62], and reduces the infarct size [63]. EA at LI11 and ST36 for 20 min once a day for 6 weeks showed a similar effect to that of the perindopril group [64].…”

Ischemic postconditioning provides cardioprotective and antiapoptotic effects against ischemia–reperfusion injury through iNOS inhibition in hyperthyroid rats

“…Nitric oxide can recover or diminish heart contractility if derived from eNOS or iNOS respectively (Rastaldo et al, 2007). Unlike disease conditions, it has been shown that IPost could provide protective effect against IR in normal conditions (Wei et al, 2015). Studies have shown that although, IPost inhibits myocardial apoptosis after IR injury, (Inamura et al, 2010;He et al, 2011), but no similar antiapoptotic effect has however been observed in diabetes rats (Drenger et al, 2011).…”