Diabetes mellitus substantially increases the risk of
stroke and enhances brain's vulnerability to
ischemia insult.
Electroacupuncture (EA) pretreatment was proved to induce cerebral ischemic tolerance in normal
stroke models. Whether EA could attenuate
cerebral ischemia injury in diabetic mice and the possible underlying mechanism are still unrevealed. Male C57BL/6 mice were subjected to
streptozotocin (STZ) for diabetic models. After inducing focal
cerebral ischemia model, the levels of plasma and cerebral
adiponectin (APN) were measured as well as the expression of cerebral
adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2). The neurobehavioral score,
infarction volume, and cellular apoptosis were evaluated with or without AdipoR1
short interfering RNA (
siRNA). The role of phosphorylation of
glycogen synthesis
kinase 3 beta (GSK-3β) at Ser-9 in the EA pretreatment was also assessed. EA pretreatment increased both plasma and cerebral APN levels and enhanced neuronal AdipoR1 in diabetic mice. In addition, EA reduced
infarct size, improved neurological outcomes, and inhibited cell apoptosis after reperfusion. These beneficial effects were reversed by AdipoR1 knockdown. Furthermore, EA increased GSK-3β phosphorylation (p-GSK-3β) in the ipsilateral penumbra. Augmented p-GSK-3β induced
neuroprotective effects similar to those of EA pretreatment. In contrast, dampened p-GSK-3β could reverse the
neuroprotective effects of EA. In addition, the increase in p-GSK-3β by EA was abolished by AdipoR1 knockdown. We conclude that EA pretreatment increases the production of APN, which induce protective effects against
cerebral ischemia-
reperfusion injury through neuronal AdipoR1-mediated phosphorylation of GSK-3β in diabetic mice.