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. 2019 May 17;9:7562. doi: 10.1038/s41598-019-44006-8

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Glutamate released from microglia is a trigger for post-septic neuronal and psychiatric illness. The effect of glutamate receptor antagonist on PSNPI. Behavioral test including (a) BW, (b) Y-maze, (c) WRA, and (d) RR with/without glutamate receptor antagonist. (a–d) Sham; n = 12, LPS; n = 13, LPS + DNQX (L + DNQX); n = 9, LPS + MK801 (L + MK801); n = 11. (a) MK801 and DNQX show a tendency to improve BW loss at 3 days after LPS treatment, but the differences are not statistically significant. F (3, 176) = 0.68, p = 0.56. (b) MK801 prevents the reduction of the Y-maze score significantly. F (3, 176) = 6.38, p < 0.001. Post hoc; LPS vs L + MK801, p < 0.01. (c) DNQX and MK801 prevents the reduction of WRA score significantly. F (3, 176) = 5.39, p < 0.005. Post hoc; LPS vs L + DNQX, p < 0.01; LPS vs L + MK801, p < 0.05. (d) The effect of MK801 and DNQX on the RR score is mild and not statistically significant. F (3, 176) = 2.85, p = 0.039. Post hoc; LPS vs L + DNQX, p = 0.15; LPS vs L + MK801, p = 0.45. (e) Relative glutamate level in extracellular space (in vivo microdialysis). Extracellular glutamate gradually increased from 8 h after LPS treatment, and statistically high level of glutamate was shown at 24 h after LPS treatment. (*p < 0.01, sham; n = 4, LPS; n = 4) (f) Released glutamate from microglia. Isolated microglia were incubated with cysteine/cystine in HBSS. Microglia isolated from LPS-treated mice release more glutamate than those from sham-treated mice. (*p < 0.01, sham; n = 14, LPS; n = 15).