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. 2020 Dec 16;10:22013. doi: 10.1038/s41598-020-78880-4

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© The Author(s) 2020

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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A plot of the D1 effect size (average % difference vs. SHAMs $\pm$ 95% CI of difference) for cell volume and density (a) across every brain region assessed in experiment 1, along with the overall experimental average effect size for each endpoint (highlighted). The traditional Munro-Kellie model of ICP compliance asserts that once a mass is added to the brain (whether that be edema and/or a hematoma), CSF and vascular blood are redirected to reduce rising ICP (b, c). In our proposed modification, the increase in neuronal packing density and reduction in cell volume that we observed in both ICH and MCAO kick in as ICP rises, aiding in compliance and reducing the required displacement of vascular blood and CSF (e), especially after large strokes (f). This may aid in avoiding secondary ischemic injury due to reduced cerebral blood flow, and potentially helps prevent transforaminal herniation. Lastly, representative cresyl violet images of hippocampal layer CA1 in both ipsilateral ICH-D1(d) and SHAM (g) tissue are shown to illustrate the tissue compliance phenomenon. Cresyl violet images were taken at 40 × magnification, and cranium diagrams (derivative of Creative Commons Licence CCO Public Domain image: https://commons.wikimedia.org/wiki/File:Human_skull_no_text_no_color.svg) were put together in Adobe Photoshop (version 21.2.1) and are not to anatomical scale. Figure was made using GraphPad Prism version 8.4.3 for macOS, GraphPad Software, San Diego, California USA, www.graphpad.com.