Electroacupuncture at the Dazhui and Baihui acupoints and different frequencies (۱۰ and ۵۰ Hz) protects against apoptosis by up-regulating ERK۱/۲-mediated signaling in rats after global cerebral ischemia

Objective(s): This study assessed the effects of electroacupuncture (EA) stimulation at different frequencies at the Dazhui and Baihui acupoints in the subacute phase after transient global cerebral ischemia (GCI). Materials and Methods: Rats were subjected to GCI for ۲۵ min, followed by reperfusion for ۷ days. EA at acupoints was performed at ۱۰, ۳۰, or ۵۰ Hz, ۱ day after reperfusion and then once daily for ۶ consecutive days. Results: EA at acupoints at ۱۰ and ۵۰ Hz effectively down-regulated apoptosis in the hippocampal cornu ammonis ۱(CA۱) area and ameliorated memory deficits. Moreover, EA treatment at ۱۰ and ۵۰ Hz markedly increased phospho (p)-extracellular signal-regulated protein kinase ۱/۲ (ERK۱/۲), p-ERK۱/۲/neuronal nuclei (NeuN), p-cAMP response element-binding protein (CREB)/p-ERK۱/۲, B-cell lymphoma-۲ (Bcl-۲)/p-CREB, and X-linked inhibitor of apoptosis protein/NeuN expression levels and decreased Bcl-۲ homologous antagonist/killer, second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI, cytochrome c, cleaved caspase-۳, and apoptosis-inducing factor expression levels. Furthermore, ۱۰-Hz EA treatment effectively increased p-p۳۸ mitogen-activated protein kinase (MAPK), p-p۳۸ MAPK/NeuN, and p-CREB/p-p۳۸ MAPK expression levels. Pretreatment with U۰۱۲۶ (ERK۱/۲ inhibitor) completely abrogated the effects of ۱۰- and ۵۰-Hz EA treatments on the aforementioned protein expression levels. Similarly, pretreatment with SB۲۰۳۵۸۰ (p۳۸ MAPK inhibitor) completely abrogated the effects of ۱۰-Hz treatment on the aforementioned protein expression levels. Conclusion: The effects of ۱۰- and ۵۰-Hz EA treatments on mitochondria-related apoptosis can be attributed to the activation of ERK۱/۲/p۳۸ MAPK/CREB/Bcl-۲- and ERK۱/۲/CREB/Bcl-۲-mediated signaling, respectively, in the hippocampal CA۱ area at ۷ days after transient GCI.

Keywords:

Apoptosis-inducing factor , Brain ischemia , Electroacupuncture , Hippocampus , MAP kinase signaling - system