Post-stroke treatment with argon preserved neurons and attenuated microglia/macrophage activation long-termly in a rat model of transient middle cerebral artery occlusion (tMCAO)

Abstract

In a previous study from our group, argon has shown to significantly attenuate brain injury, reduce brain inflammation and enhance M2 microglia/macrophage polarization until 7 days after ischemic stroke. However, the long-term effects of argon have not been reported thus far. In the present study, we analyzed the underlying neuroprotective effects and potential mechanisms of argon, up to 30 days after ischemic stroke. Argon administration with a 3 h delay after stroke onset and 1 h after reperfusion demonstrated long-term neuroprotective effect by preserving the neurons at the ischemic boundary zone 30 days after stroke. Furthermore, the excessive microglia/macrophage activation in rat brain was reduced by argon treatment 30 days after ischemic insult. However, long-lasting neurological improvement was not detectable. More sensorimotor functional measures, age- and disease-related models, as well as further histological and molecular biological analyses will be needed to extend the understanding of argon’s neuroprotective effects and mechanism of action after ischemic stroke.

Argon neuroprotection in a non-human primate model of transient endovascular ischemic stroke

“…Moreover, we observed a better neurological outcome in neuroprotected animals, but this observation remains qualitative due to the limited size of our experimental groups. Overall, our results confirm the neuroprotective effects of argon inhalation observed in rat models of MCAO in terms of both infarct volumes[11,12,14] and neurological dysfunction[23,24]. However, in contrast to these rodent studies, we showed that the neuroprotective effect is limited to the cortical sheet, which was mainly affected in our NHP model of tMCAO.…”

Treatment with inhaled Argon: a systematic review of pre-clinical and clinical studies with meta-analysis on neuroprotective effect

“…There were 16 in vitro studies, seven ex vivo studies, and 37 in vivo studies (six of which also included in vitro experiments). 1 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 Details of these studies are presented in the Supplemental materials ( Supplemental Tables S7 and S8 ). The sex of humans, animals, cells, and tissues involved are documented in Supplemental Table S7 (under the column labelled “cell tissue”) and…”

“…3 , panel a). 18 , 19 , 20 , 22 , 23 , 24 , 25 , 26 , 27 , 29 , 30 , 31 , 32 , 40 , 41 , 43 , 44 , 45 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 60 , 62 , 63 , 64 , 67 , 68 , 69 , 71 , 73 , 74 , 75 , 76…”

“…A total of thirty-seven in vivo studies investigating Ar as potential protective agent for different organs (brain, heart, kidney, and liver) were found ( Supplemental Table S8 ). 1 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76…”

Argon mitigates post-stroke neuroinflammation by regulating M1/M2 polarization and inhibiting NF-κB/NLRP3 inflammasome signaling

“…Therefore, argon draws more and more attention as a promising new treatment for stroke. It is reported that argon exposure attenuates neuroinflammation and injury whereas enhances M2 microglia/macrophage polarization in rat tMCAO model ( Liu et al., 2019 , 2022 ). However, the effect of argon on M1 microglia/macrophage and NLRP3 inflammasome has not been reported, and the mechanism underlying the neuroprotective properties of argon is not fully understood yet.…”