Electroacupuncture Preconditioning Ameliorates the Ischemic Microenvironment to Improve Long-Term Potentiation in Chronic Cerebral Hypoperfusion Rats With MGE Neural Progenitor Transplantation.

Abstract

Background: Vascular cognitive impairment (VCI) is the second most common type of cognitive impairment in the world after Alzheimer's disease (AD). At present, there is no specific drug for VCI. This study aims to confirm the role of electroacupuncture (EA) preconditioning in improving the long-term potentiation (LTP) of chronic cerebral hypoperfusion (CCH) rats with human embryonic stem cell (hESC)-derived medial ganglionic eminence (MGE) neural progenitor transplantation and to investigate its possible mechanism. Methods: Rats with two-vessel occlusion (2VO) were selected as models for the study of VCI. The rats in the 2VO + cell + EA group were given EA for 7 days after modeling. On the 7^th day, MGE neural progenitors were transplanted into the hippocampus of CCH rats. 2 weeks after transplantation, we detected the expressions of Iba1, CX3CL1/CX3CR1, Bcl2/Bax, brain-derived neurotrophic factor (BDNF), and tyrosine receptor kinase B (TrkB) in the hippocampus of rats by western blot. Immunofluorescence staining was used to observe the morphologies of microglia and the survival and differentiation of transplanted cells. Microglial morphologies were quantitatively analyzed using the AnalyzeSkeleton. 8 weeks after transplantation, the LTP in the hippocampus of brain slices was detected to evaluate the learning and memory function of the rats with CCH. Results: 2 weeks after transplantation, we observed that MGE neural progenitors survived and differentiated into neurons in the hippocampus of CCH rats. Inflammation and apoptosis appeared in the hippocampus of rats after the interruption of cerebral blood flow. EA preconditioning notably alleviated the inflammatory response and inhibited cell apoptosis in the hippocampus. Moreover, we detected that the expressions of BDNF and TrkB were increased in the hippocampus of rats in the 2VO + cell group and 2VO + cell + EA groups, especially in the 2VO + cell + EA groups. 8 weeks after transplantation, the electrophysiological experiment results showed that the LTP value in the 2VO group was 103.1% ± 2.316%. Compared with the 2VO group, LTP value increased in the 2VO + cell group and 2VO + cell + EA group, which were 136.2% ± 1.603% and 170.8% ± 15.82%, respectively. The increase of LTP value in the 2VO + cell + EA group was more obvious. Conclusion: MGE neural progenitor transplantation improves the LTP of CCH rats, and EA preconditioning can enhance the efficacy of cell transplantation. This enhancement mechanism may be attributed to the effect of EA preconditioning on ameliorating the ischemic microenvironment.