Involvement of P2X7R-mediated microglia polarization and neuroinflammation in the response to electroacupuncture on post-stroke memory impairment.

PURPOSE: Post-stroke cognitive impairment (PSCI) is a common complication of ischemic stroke episodes. Memory impairment is an important component of the poststroke cognitive syndrome. Microglial activation plays a critical role in stroke-induced neuroinflammation. Previous studies have reported that electroacupuncture (EA) provides neuroprotective effects by reducing the expression levels of the Purinergic receptor P2X ligand-gated ion channel 7 (P2X7) and inhibiting neuroinflammation in rat model of ischemic stroke. Further understanding of the role and connections between P2X7R and microglial activation in EA-induced anti-inflammatory can reveal novel targets for post-stroke memory impairment treatment. METHODS: A Middle cerebral artery occlusion and reperfusion (MCAO/R) model was established. We used 2'(3')-O-(4-benzoyl) benzoyl ATP (BzATP) as a P2X7R agonist. Following MCAO/R injury, the rats underwent EA therapy at the Baihui (DU20) and Shenting (DU24) acupoints for seven consecutive days. The Barnes maze test was used to evaluate memory function. Following intervention, a T2 weighted images (T2WI) scan was performed to identify changes in cerebral infarction volume in MCAO/R rats. The levels of Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) and Interleukin-4 (IL-4), Interleukin-10 (IL-10) in the peri-infarct hippocampal were examined by ELISA. Immunofluorescence was employed to evaluate Iba-1+ / P2X7R+, Iba-1+/ iNOS+ and Iba-1+/ Arg-1+ cell populations in the peri-infarct hippocampal DG area. The protein expression of P2X7R, Nuclear factor E2-related factor 2 (Nrf2), Recombinant nlr family, pyrin domain containing protein 3 (NLRP3), Inducible nitric oxide synthase (iNOS) and Arginase-1 (Arg-1) in the peri-infarct hippocampal were investigated using western blot assays. Besides, we also measured the levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA). RESULTS: We found EA treatment reduced inflammation and oxidative stress, which is consistent with a decrease in P2X7R expression and improved learning and memory functions. In contrast, we found BzATP enhanced inflammation and oxidative stress. Moreover, our results showed EA treatment up-regulated Nrf2, down-regulated NLRP3, and promoted microglia M2 polarization. Finally, EA-mediated positive effects were reversed by intracerebroventricular injection of BzATP, which is consistent with an increase in P2X7R expression. CONCLUSION: EA ameliorates memory impairment in a rat model of ischemic stroke by reducing inflammation and ROS through the inhibition of P2X7R expression. In turn, this mechanism regulates Nrf2 and NLRP3 expression, suggesting EA is beneficial for ischemic stroke treatment using P2X7R as target.

Conical Statistical Optimal Near-Field Acoustic Holography with Combined Regularization.

For the sound field reconstruction of large conical surfaces, current statistical optimal near-field acoustic holography (SONAH) methods have relatively poor applicability and low accuracy. To overcome this problem, conical SONAH based on cylindrical SONAH is proposed in this paper. Firstly, elementary cylindrical waves are transformed into those suitable for the radiated sound field of the conical surface through cylinder-cone coordinates transformation, which forms the matrix of characteristic elementary waves in the conical spatial domain. Secondly, the sound pressure is expressed as the superposition of those characteristic elementary waves, and the superposition coefficients are solved according to the principle of superposition of wave field. Finally, the reconstructed conical pressure is expressed as a linear superposition of the holographic conical pressure. Furthermore, to overcome ill-posed problems, a regularization method combining truncated singular value decomposition (TSVD) and Tikhonov regularization is proposed. Large singular values before the truncation point of TSVD are not processed and remaining small singular values representing high-frequency noise are modified by Tikhonov regularization. Numerical and experimental case studies are carried out to validate the effectiveness of the proposed conical SONAH and the combined regularization method, which can provide reliable evidence for noise monitoring and control of mechanical systems.