Mechanisms of atmospheric pressure plasma protection of neuronal cells under simulated ischemic stroke conditions

Physico-chemical and biological effects of atmospheric pressure plasmas (APPs) find numerous applications in biotechnology, medicine, and other fields. Recent studies revealed APPs' potential for ischemic stroke treatment through the protection of neuronal cells from injuries. However, the mechanisms of the plasma neuroprotection effects still remain unknown. This study reveals the key mechanisms of APP plasma jet (APPJ) enabled reduction of neuronal cell death caused by oxygen and glucose deprivation (OGD) under stroke-relevant conditions. Plasma reduced OGD induced apoptosis of SH-SY5Y neuronal cells is based on reactive oxygen and nitrogen species production and on nitric oxide related activation of the cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase G (PKG) pathway, followed by the Bcl-2/Bax level modulation and caspase3/9 activity inhibition. In addition, the protective effect of APPJ treatment on OGD injured SH-SY5Y cells could be abolished by cGMP pathway inhibitor LY83583 pretreatment. Collectively, our findings highlight that the mechanism of the neuroprotection effects of the plasma treatment is closely related to the intracellular cGMP/PKG pathway, which provide experimental and theoretical references for future studies on plasma medicine.