Scalp Electroacupuncture Promotes Angiogenesis after Stroke in Rats by Activation of Wnt/β-Catenin Signal Pathway

Abstract

Background. Scalp acupuncture is a contemporary acupuncture method based on the fundamental theories of traditional acupuncture, which has been widely used in patients with stroke in China. However, the effectiveness is controversial due to lack of solid experimental evidence. Methods. In this study, a rat model of cerebral ischemia-reperfusion injury (CIRI) was established by the middle cerebral artery occlusion/recirculation. The efficacy of scalp acupuncture against CIRI was evaluated by the mNSS scores, TTC staining for brain slices, and laser Doppler perfusion imaging. Immunohistochemical staining for angiogenetic factors indicated the vascularization after CIRI, including VEGF, Ang2, and bFGF. Activation of the Wnt/β-catenin signaling pathway and p-GSK3β (ser9)/VEGF pathway in the injured brain tissues was assessed by western blotting and qRT-PCR. Results. On the 7, 14, and 21 days after CIRI, scalp acupuncture could reduce the mNSS scores, decrease the cerebral infarction area, and accelerate the recirculation of ischemic brain tissues. VEGF, FLK1, bFGF, and Ang2 were upregulated on both the mRNA and protein levels in the ischemic brain tissues of the AC group, suggesting that the recirculation might result from angiogenesis, which was also confirmed with the IHC staining in the angiogenetic markers of VEGF, Ang2, and bFGF. Moreover, Wnt3a, β-catenin, and cyclin D1 were also upregulated on both the mRNA and protein levels in the ischemic brain tissues of the AC group on day 7, 14, and 21, indicating that the Wnt/β-catenin signaling pathway was activated after the treatment of scalp acupuncture. In contrast, dikkoppf-1 (DKK1) pretreatment, a specific inhibitor for the Wnt/β-catenin signaling pathway, inactivated the Wnt3a/β-catenin signaling pathway and exacerbated the infarct size induced by the cerebral IR injury on day 7. Conclusion. Together, our findings demonstrated a mechanism whereby scalp acupuncture led to the activation of Wnt/β-catenin signaling pathway, promoting angiogenetic factor expression and restoring blood perfusion in the ischemic zone.

Bibliometric analysis: Hot spots and frontiers in acupuncture treatment of cerebral infarction

“…Sha et al [ 28 ] believe that acupuncture can relieve neuronal inflammation by inhibiting miR-223/NLRP3 pathway, thus playing a protective role for nerves. Shi et al [ 29 ] reported that acupuncture was able to activate the Wnt/β-catenin signaling pathway and up-regulate angiogenesis factor expression, thereby promoting angiogenesis after cerebral infarction. In promoting neural tissue remodeling, studies have shown that [ 30 , 31 ] acupuncture can activate nerve growth factors and promote the proliferation of neural stem cells.…”

Recent advances in tissue repair of the blood-brain barrier after stroke

“… 186 In addition, applying EA at GV20 can activate the expression of VEGF mediated by Wnt/β-catenin signaling pathway, thereby promoting angiogenesis and restoring blood perfusion in ischemic areas. 187 The miR-210 extracted from the serum of diseased mice treated with EA (EA-EXO) can increase the levels of HIF-1α, VEGF, and Notch1 proteins in rats with cerebral ischemia and promote angiogenesis. 188 …”

Trends in Acupuncture Therapy for Microcirculation and Hemorheology from 1998 to 2023: A Bibliometric and Visualized Study

“…Studies show electroacupuncture increases EPC quantity and accelerates EC growth. 58 Moreover, acupuncture may stimulate angiogenesis via Vascular Endothelial Growth Factor (VEGF), 59 EphB4/EphrinB2, 60 SDF-1α/CXCR4, 58 and Apelin/APJ pathways. 61…”