Abstract
BackgroundThis study aimed to determine the effects of electroacupuncture stimulation at the Baihui (GV20) and Fengfu (GV16) acupoints, at frequencies of 5Hz (EA-5Hz) and 25Hz (EA-25Hz), 7 days after cerebral ischemia-reperfusion (I/R) injury, and to evaluate the possible signaling mechanisms involved in mitogen-activated protein kinase (MAPK) pathways.MethodsRats were subjected to 30 min of middle cerebral artery occlusion (MCAo) followed by 7 days of reperfusion. EA-5Hz or EA-25Hz was applied immediately after MCAo and then once daily for 7 consecutive days.ResultsResults indicated that EA-5Hz and EA-25Hz both markedly attenuated cerebral infarction and neurological deficits. EA-5Hz and EA-25Hz both markedly downregulated cytosolic glial fibrillary acidic protein (GFAP), mitochondrial Bax, mitochondrial and cytosolic second mitochondrial-derived activator of caspase/direct inhibitor of apoptosis protein-binding protein with low isoelectric point (Smac/DIABLO), and cytosolic cleaved caspase-3 expression, and effectively restored cytosolic phospho-p38 MAPK (p-p38 MAPK), cytosolic cAMP response element-binding protein (CREB), mitochondrial Bcl-xL, and cytosolic X-linked inhibitor of apoptosis protein (XIAP) expression, in the ischemic cortical penumbra 7 days after reperfusion. Both EA-5Hz and EA-25Hz also significantly increased the ratios of mitochondrial Bcl-xL/Bax and Bcl-2/Bax, respectively.ConclusionsBoth EA-5Hz and EA-25Hz effectively downregulate reactive astrocytosis to provide neuroprotection against cerebral infarction, most likely by activating the p38 MAPK/CREB signaling pathway. The modulating effects of EA-5Hz and EA-25Hz on Bax-mediated apoptosis are possibly due to the activation of p38 MAPK/CREB/Bcl-xL and p38 MAPK/CREB/Bcl-2 signaling pathways, respectively, and eventually contribute to the prevention of Smac/DIABLO translocation and subsequent restoration of XIAP-mediated suppression of caspase-3 in the cortical periinfarct area 7 days after reperfusion.
Highlights
This study aimed to determine the effects of electroacupuncture stimulation at the Baihui (GV20) and Fengfu (GV16) acupoints, at frequencies of 5Hz (EA-5Hz) and 25Hz (EA-25Hz), 7 days after cerebral ischemia-reperfusion (I/R) injury, and to evaluate the possible signaling mechanisms involved in mitogen-activated protein kinase (MAPK) pathways
In this study, we aimed to evaluate the effects of EA stimulation at the Baihui and Fengfu acupoints (EA at acupoints), at a frequency of 5 or 25Hz, after 30 min of cerebral ischemia followed by 7 days of reperfusion, and to evaluate the possible involvement of MAPK cascades in the ischemic cortical penumbra
Effects of EA-5Hz and EA-25Hz on cerebral infarct area The rats developed prominent cerebral infarction after 30 min of middle cerebral artery occlusion (MCAo) followed by 7 days of reperfusion (P < 0.05 vs. Sham group; Figs. 1 and 2a)
Summary
This study aimed to determine the effects of electroacupuncture stimulation at the Baihui (GV20) and Fengfu (GV16) acupoints, at frequencies of 5Hz (EA-5Hz) and 25Hz (EA-25Hz), 7 days after cerebral ischemia-reperfusion (I/R) injury, and to evaluate the possible signaling mechanisms involved in mitogen-activated protein kinase (MAPK) pathways. MAPKs might play roles in the regulation of cell death and survival, depending on the cell type and cerebral ischemic model [5]. Studies have indicated that p38 MAPK activation upregulates the expression of the cAMP response element-binding protein (CREB)-regulated cell survival proteins Bcl-2 and Bcl-xL in cerebral ischemic preconditioning models [7,8,9]. The Bcl-2 family proteins, including Bcl-2, Bcl-xL, and Bax, play pivotal roles in regulating mitochondria-mediated apoptotic pathway. Following activation of the apoptotic signaling cascade after cerebral I/R injury, Bax/Bcl-2 and Bax/Bcl-xL heterodimers are rapidly dissociated, and the monomeric form of Bax translocates from the cytosol to the mitochondrial membrane, where it is cross-linked as a Bax homodimer, and opens the mitochondrial permeability transition pore. Mature Smac/DIABLO interacts with XIAP in the cytosol, which abrogates the anticaspase function of XIAP and triggers caspase-3 dependent apoptosis [15]
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