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Papers of the Week


Papers: 22 Jun 2019 - 28 Jun 2019


Animal Studies


2020 May


J Cereb Blood Flow Metab


40


5

Non-invasively triggered spreading depolarizations induce a rapid pro-inflammatory response in cerebral cortex.

Authors

Takizawa T, Qin T, Lopes de Morais A, Sugimoto K, Chung J Y, Morsett L, Mulder I, Fischer P, Suzuki T, Anzabi M, Böhm M, Qu W-S, Yanagisawa T, Hickman S, Khoury J E, Whalen MJ, Harriott AM, Chung DY, Ayata C
J Cereb Blood Flow Metab. 2020 May; 40(5):1117-1131.
PMID: 31242047.

Abstract

Cortical spreading depolarization (CSD) induces pro-inflammatory gene expression in brain tissue. However, previous studies assessing the relationship between CSD and inflammation have used invasive methods that directly trigger inflammation. To eliminate the injury confounder, we induced CSDs non-invasively through intact skull using optogenetics in Thy1-channelrhodopsin-2 transgenic mice. We corroborated our findings by minimally invasive KCl-induced CSDs through thinned skull. Six CSDs induced over 1 h dramatically increased cortical , and mRNA expression peaking around 1, 2 and 4 h, respectively. and were only modestly elevated. A single CSD also increased , and , and revealed an ultra-early response within 10 min. The response was blunted in IL-1 receptor-1 knockout mice, implicating IL-1β as an upstream mediator, and suppressed by dexamethasone, but not ibuprofen. CSD did not alter systemic inflammatory indices. In summary, this is the first report of pro-inflammatory gene expression after non-invasively induced CSDs. Altogether, our data provide novel insights into the role of CSD-induced neuroinflammation in migraine headache pathogenesis and have implications for the inflammatory processes in acute brain injury where numerous CSDs occur for days.