Journal
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
Volume 31, Issue 9, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jstrokecerebrovasdis.2022.106596
Keywords
Reperfusion injury; Vagus nerve stimulation; Microglial polarization; Toll-like receptor 4
Categories
Funding
- National Natural Sci- ence Foundation of China [81900079]
- Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0238]
- Chongqing Municipal Health Commission [2020MSXM037]
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The study found that VNS can promote the conversion of microglia from M1 to M2 phenotype, alleviate inflammatory response and brain injury, and exert its effects by inhibiting the TLR4/MyD88/NF-kB pathway.
Objective: To specify the effect of vagus nerve stimulation (VNS) on microglial polar-ization following ischemic-reperfusion and further investigate its underlying mech-anism. Materials and methods: Sprague-Dawley rats were randomly divided into the sham, ischemic reperfusion group (IR), IR+VNS groups. VNS intervention lasting for 1 hour was administered after 30 minutes of occlusion. We analyzed the expression of Arginase 1 (Arg1), the number of M2 microglial in the peri-infarction cortex and assessed the neurological scores at the 1, 3, 7 days after reperfusion to deter-mine the research time point. Then, we assessed polarization status of microglial, the infarct volume, neurological scores, the cellular distribution of Toll-like Recep-tor 4 (TLR4), the TLR4-associated pathway protein and the p-NF-kB in microglial at 3 days after reperfusion. Results: We found that VNS could increase the specific marker of M2 Arg1 and upregulate the M2 microglial after reperfusion, and the increase of Arg1, M2 microglial and the neurological scores was largest at the 3 days after reperfusion. VNS treatment significantly reduced the number and per-cent of M1, improved the number and percent of M2 and upregulated the M2 to M1 ratio without changing the number of total microglial at the 3 days after reperfusion. Moreover, VNS reduced the infarct volume and neurological deficits. In addition, VNS significantly reduced the microglial-specific TLR4, inhibited the activated TLR4/MyD88/NF-kB pathway following ischemic-reperfusion, and ultimately suppressed the p-NF-kB in microglial. Conclusion: Our study revealed that VNS can promote the M1-to-M2 phenotype conversion to alleviate inflammatory response and brain injury through inhibition of TLR4/MyD88/NF-kB pathway in microglia following ischemic-reperfusion. (C) 2022 Elsevier Inc. All rights reserved.
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