Electroacupuncture Promotes the Survival of the Grafted Human MGE Neural Progenitors in Rats with Cerebral Ischemia by Promoting Angiogenesis and Inhibiting Inflammation.

Stem cells have the potential as a regenerative therapy for cerebral ischemia by improving functional outcomes. However, cell transplantation has some limitations, including a low rate of the grafted cell survival. There is still a major challenge of promoting the harmonious symbiosis between grafted cells and the host. Acupuncture can effectively improve the functional outcome after cerebral ischemia. The present study evaluated the therapeutic effects and explored the mechanism of combined medial ganglionic eminence (MGE) neural progenitors differentiated from human embryonic stem cells (hESCs) with electroacupuncture (EA) in a bilateral common carotid artery occlusion (2VO) rat model. The results showed that EA could promote the survival of the grafted MGE neural progenitors differentiated from hESCs and alleviate learning and memory impairment in rats with cerebral ischemia. This may have partially resulted from inhibited expression of TNF-α and IL-1ß and increased vascular endothelial growth factor (VEGF) expression and blood vessel density in the hippocampus. Our findings indicated that EA could promote the survival of the grafted MGE neural progenitors and enhance transplantation therapy's efficacy by promoting angiogenesis and inhibiting inflammation.

The Effects of Electroacupuncture in a Rat Model of Cerebral Ischemia-Reperfusion Injury Following Middle Cerebral Artery Occlusion Involves MicroRNA-223 and the PTEN Signaling Pathway.

BACKGROUND In China, electroacupuncture (EA) is used to treat the symptoms of ischemic stroke. However, the mechanisms involved in the effects of EA in cerebral ischemia remain to be investigated. This study aimed to investigate the molecular mechanism underlying the effects of EA in a rat model of cerebral ischemia-reperfusion injury (CIRI) induced by middle cerebral artery occlusion (MCAO). MATERIAL AND METHODS Seventy-five male Sprague-Dawley rats were divided into five groups: the sham group (with sham surgery), the model group (the MCAO model), the EA group (treated with EA), the EA control group, and the EA+antagomir-223-3p group. Rats in the model of CIRI underwent MCAO for 90 minutes. EA was performed on the second postoperative day and was performed at the Waiguan (TE5) and Zusanli (ST36) acupoints. The rat brains were evaluated for structural and molecular markers. RESULTS EA treatment significantly upregulated the expression of microRNA-223 (miR-223), NESTIN, and NOTCH1, and downregulated the expression of PTEN in the subventricular zone (SVZ) and hippocampus. The luciferase reporter assay supported that PTEN was a direct target of miR-223, and antagomiR-223-3p reversed the effects of EA and reduced the increase in NESTIN and inhibition of PTEN expression associated with EA treatment. There was a negative correlation between PTEN expression and the number of neural stem cells (NSCs). CONCLUSIONS In a rat model of CIRI following MCAO, EA activated the NOTCH pathway, promoted the expression of miR-223, increased the number of NSCs, and reduced the expression of PTEN.

Electroacupuncture Alleviates Ischemic Brain Injury by Inhibiting the miR-223/NLRP3 Pathway.

BACKGROUND Electroacupuncture (EA) has been commonly used to treat stroke in China. However, the underlying mechanism remains largely unknown. The present study investigated the neuroprotective effects of EA in middle cerebral artery occlusion (MCAO) rats and elucidated the possible anti-inflammatory mechanisms. MATERIAL AND METHODS In this study, modified neurological severity scoring (mNSS) was used to assess neurological deficits, and TTC staining and brain water content were measured to evaluate the degree of brain damage. HE staining, Nissl staining, and TUNEL staining were employed to evaluate apoptotic neuronal death. Molecular biological methods were used to measure the levels of miR-233, NLRP3, caspase-1, IL-1ß, and IL-18 in the peri-infarct cortex. RESULTS Our results showed that EA treatment significantly decreased the neurological deficit score and infarct volume of MCAO rats. The level of miR-223 was increased, while the levels of NLRP3, caspase-1, IL-1ß, and IL-18 were decreased in the peri-infarct cortex of EA-treated MCAO rats. However, the neuroprotective effect of EA was partially blocked by antagomir-223. CONCLUSIONS These data suggest that EA treatment can alleviate neuroinflammation by inhibiting the miR-223/NLRP3 pathway, thus playing a neuroprotective role in MCAO in rats.

Electroacupuncture Ameliorates Learning and Memory and Improves Synaptic Plasticity via Activation of the PKA/CREB Signaling Pathway in Cerebral Hypoperfusion.

Electroacupuncture (EA) has shown protective effects on cognitive decline. However, the underlying molecular mechanisms are ill-understood. The present study was undertaken to determine whether the cognitive function was ameliorated in cerebral hypoperfusion rats following EA and to investigate the role of PKA/CREB pathway. We used a rat 2-vessel occlusion (2VO) model and delivered EA at Baihui (GV20) and Dazhui (GV14) acupoints. Morris water maze (MWM) task, electrophysiological recording, Golgi silver stain, Nissl stain, Western blot, and real-time PCR were employed. EA significantly (1) ameliorated the spatial learning and memory deficits, (2) alleviated long-term potentiation (LTP) impairment and the reduction of dendritic spine density, (3) suppressed the decline of phospho-CREB (pCREB) protein, brain-derived neurotrophic factor (BDNF) protein, and microRNA132 (miR132), and (4) reduced the increase of p250GAP protein of 2VO rats. These changes were partially blocked by a selective protein kinase A (PKA) inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H89), suggesting that the PKA/CREB pathway is potentially involved in the effects of EA. Moreover, any significant damage to the pyramidal cell layer of CA1 subregion was absent. These results demonstrated that EA could ameliorate learning and memory deficits and alleviate hippocampal synaptic plasticity impairment of cerebral hypoperfusion rats, potentially mediated by PKA/CREB signaling pathway.

Electroacupuncture Ameliorates Learning and Memory via Activation of the CREB Signaling Pathway in the Hippocampus to Attenuate Apoptosis after Cerebral Hypoperfusion.

Studies have shown that electroacupuncture (EA) ameliorates learning and memory after ischemic injury. However, there have been few studies elucidating the mechanisms of EA on learning and memory in cerebral hypoperfusion. In this study, we explored the cAMP response element-binding protein (CREB) signaling pathway-mediated antiapoptotic action involved in EA-induced improvement of learning and memory. EA at GV20 and GV14 acupoints was applied in cerebral hypoperfusion rats. A Morris water maze task was performed, and the immunoreactivities of pCREB, Bcl-2, and Bax in the hippocampal CA1 area were evaluated by the Western blotting technique. Our findings indicated that (1) EA ameliorated spatial learning and memory impairment in cerebral hypoperfusion rats; (2) EA increased the immunoreactivities of pCREB and Bcl-2 and decreased the immunoreactivity of Bax; (3) intracerebroventricular administration of H89 (the inhibitor of protein kinase A) blocked EA-induced, pCREB-mediated antiapoptotic action and improved learning and memory. These results suggest that EA can ameliorate learning and memory via activation of the CREB signaling pathway in the hippocampus to attenuate apoptosis after cerebral hypoperfusion.

A study of astrocyte activation in the periinfarct region after cerebral ischemia with electroacupuncture.

OBJECTIVE: To investigate the effects of electroacupuncture (EA) on the activation of astrocytes (AST) in the periinfarct region after cerebral ischemia, as well as to evaluate potential behavioural improvement after EA treatment. METHODS: Male Wistar rats were randomly divided into normal, model and EA groups. Rats in each group were further divided into 7, 14 and 28 days sub-groups. A model of middle cerebral artery occlusion was established, followed by 7, 14 or 28 days of EA on 'Bai hui' and 'Da zhui' acupoints. The number of GFAP-immunoreactive cells was determined and behavioural tests were performed. RESULTS: Many more GFAP-immunoreactive cells were detected in the EA group on day 14 than on day 7 after ischemia and a slightly decreased number of immunoreactive cells were observed on day 28. The results of behavioural tests of animals in the EA group on the beam balance performance and prehensile traction performance were superior to that of animals in the model group. CONCLUSION: These findings indicate that EA has the potential to activate AST in the periinfarct region and to avoid excess reactive gliosis and also can facilitate the recovery of post-ischemic behavioural dysfunction.