Abstract
Transcranial direct-current stimulation (tDCS) is proved safe and shows therapeutic effect in cerebral ischemic stroke in clinical trials. But the underlying molecular mechanisms remain unclear. Here we show that tDCS treatment reduces the infarct volume after rat cerebral ischemia-reperfusion (I/R) injury and results in functional improvement of stroke animals. At the cellular and molecular level, tDCS suppresses I/R-induced upregulation of Cezanne in the ischemic neurons. Cezanne inhibition confers neuroprotection after rat I/R and oxygen glucose deprivation (OGD) in the cortical neuronal cultures. Inhibiting Cezanne increases the level of SIRT6 that is downregulated in the ischemic neurons. Suppressing SIRT6 blocks Cezanne inhibition-induced neuroprotective effect and overexpressing SIRT6 attenuates OGD-induced neuronal death. We further show that downregulating Cezanne reduces DNA double-strand break (DSB) through upregulation of SIRT6 in OGD-insulted neurons. Together, this study suggests that Cezanne-dependent SIRT6-DNA DSB signaling pathway may mediate the neuroprotective effect of tDCS in ischemic neurons.
Highlights
Stroke is the leading cause of death and long-term disability [1]
These results suggest that Transcranial direct-current stimulation (tDCS) downregulates I/R-induced increase of Cezanne in the ischemic neurons
Downregulating Cezanne protects against oxygen glucose deprivation (OGD)-induced neuronal death
Summary
Stroke is the leading cause of death and long-term disability [1]. Ischemic stroke is caused by arterial embolism, resulting in cerebral hypoxia and glucose deficiency. Blood reperfusion is essential for reducing brain cell damage, blood supply recovery after a period of ischemia leads to ischemiareperfusion (I/R) injury [2]. Transcranial direct-current stimulation (tDCS) is a noninvasive brain stimulation and has been proven safe and shown neuroprotective effect for stroke patients in clinical trials [3,4,5]. Experimental studies have shown that tDCS significantly protects against ischemic neuronal death and reduces the neurological impairment in rat middle cerebral artery occlusion (MCAO) [6,7]. The cellular and molecular mechanisms mediating the neuroprotective effect of tDCS remain unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
