{"id":671932,"date":"2025-10-07T12:00:04","date_gmt":"2025-10-07T16:00:04","guid":{"rendered":"https:\/\/www.rochester.edu\/newscenter\/?p=671932"},"modified":"2025-11-19T15:21:08","modified_gmt":"2025-11-19T20:21:08","slug":"brain-on-chip-technology-how-diseases-damage-brain-671932","status":"publish","type":"post","link":"https:\/\/www.rochester.edu\/newscenter\/brain-on-chip-technology-how-diseases-damage-brain-671932\/","title":{"rendered":"Brain-on-a-chip technology reveals how sepsis and neurodegenerative diseases damage the brain"},"content":{"rendered":"<h2><strong>The cutting-edge tool demonstrates how the blood-brain barrier breaks down and how healthy brains keep it strong.<\/strong><\/h2>\n<p>In lieu of animal experiments, researchers from the <a href=\"https:\/\/www.rochester.edu\/\">University of Rochester<\/a> are using state-of-the-art microchips with human tissue to better understand how the brain operates under healthy conditions and is damaged through neurodegenerative diseases or conditions like sepsis.<\/p>\n<p><a href=\"https:\/\/hajim.rochester.edu\/bme\/people\/faculty\/mcgrath_james\/index.html\">James McGrath<\/a>, the William R. Kenan Jr. Professor of\u00a0<a href=\"http:\/\/hajim.rochester.edu\/bme\/\">Biomedical Engineering<\/a>\u00a0and director of the <a href=\"https:\/\/www.hajim.rochester.edu\/trace-bmps\/\">Translational Center for Barrier Microphysiological Systems<\/a> (TraCe-bMPS), leads a team that develops and leverages tissue chips to study diseases where two different types of tissue meet, including at the blood-brain barrier. A pair of recent studies published in <a href=\"https:\/\/doi.org\/10.1002\/advs.202508271\"><em>Advanced Science<\/em><\/a> and <a href=\"https:\/\/doi.org\/10.1016\/j.mtbio.2025.102361\"><em>Materials Today Bio<\/em><\/a> used the chips to identify how the blood-brain barrier breaks down under serious threats, which could lead to new treatments to keep brains healthy.<\/p>\n<h3><strong>When inflammation harms the brain<\/strong><\/h3>\n<p>When a patient undergoes a major surgery or contracts an infection such as sepsis, it can excessively inflame organs throughout the body including the brain, sometimes leading to long-lasting cognitive impairment, especially in older patients.<\/p>\n<p>In a <a href=\"https:\/\/doi.org\/10.1002\/advs.202508271\">study published in <em>Advanced Science<\/em><\/a>, McGrath\u2019s team used tissue chips to show what happens at the barrier when the body suffers a cytokinetic storm\u2014when the immune system creates an uncontrollable systemic inflammatory response. Their experiments showed that with a high enough cytokine storm, the blood-brain barrier breaks down, leading to brain injury.<\/p>\n<p>\u201cTwo different stress signals\u2014blood proteins that leak into the brain, like fibrinogen, together with inflammatory cytokines\u2014can work together to trigger harmful changes in brain support cells called astrocytes,\u201d says Kaihua Chen, a biomedical engineering PhD student and lead author of the study. \u201cAt the same time, we found that the natural force of blood flow helps the blood-brain barrier stay stronger against these challenges. To me, this shows how both biology and engineering principles can come together to give us new insights into how the brain protects itself\u2014and what goes wrong in disease.\u201d<\/p>\n<p>McGrath says that in the future, the team hopes to integrate more components of the brain on the brain side of the chip, including critical immune cells in the brain known as the microglia, to better understand how neurons are damaged during these inflammatory events. Ultimately, he hopes the chips can be used to prevent brain injuries in patients undergoing cytokine storms.<\/p>\n<p>\u201cWe hope that by building these tissue models in chip format, we can arrange many brain models in a high-density array to screen candidates for neuroprotective drugs and develop brain models with diverse genetic backgrounds, including those that may be vulnerable or resilient to cytokine storms,\u201d says McGrath.<\/p>\n<p>The researchers also envision their models being used in personalized medicine, tailored to individual patients\u2019 needs.<\/p>\n<p>\u201cIf a patient is about to undergo a chemotherapy or a major surgery that risks generating cytokine storm, a chip modeling that specific patient\u2019s brain tissue could be used to evaluate risk and guide drug choice and dosing to help prevent brain injury as an outcome,\u201d McGrath says.<\/p>\n<h3><strong>A missing key to brain health<\/strong><\/h3>\n<p>A <a href=\"https:\/\/doi.org\/10.1016\/j.mtbio.2025.102361\">second study<\/a>, published in <em>Materials Today Bio<\/em>, looked at pericytes, which are support cells that play an important but still not fully understood role in maintaining the blood-brain barrier. Previous studies have shown that in cases of systemic inflammation and neurodegenerative diseases, there are far fewer pericytes than in healthy brains, but it was not fully known why.<\/p>\n<p>McGrath\u2019s team engineered holes and defects in endothelial tissue\u2014the groups of cells that form blood vessels\u2014 and introduced pericytes to see what would happen.<\/p>\n<p>\u201cIt\u2019s difficult for endothelial cells to create a proper barrier when they\u2019re dealing with these large holes,\u201d says McGrath. \u201cWhen we add the pericytes to the membrane, they create a beautiful matrix of structural fibers that fill those holes so the endothelial cells can make their vital barrier function.\u201d<\/p>\n<p>Demonstrating the interaction between pericytes and endothelial cells opens the door to therapeutics that can preserve or introduce more pericytes to help keep the blood-brain barrier stable.<\/p>\n<p>\u201cBy creating defects in the endothelial cell layer, we\u2019re letting the cells interact more directly, allowing the pericytes to provide some of the support they do in the body,\u201d says Michelle Trempel, a biomedical engineering PhD student and lead author of the study. \u201cThis is important because pericyte loss is implicated in many neurodegenerative diseases, so having a model where pericytes are providing support lets us study the impact of pericyte loss in the future.&#8221;<\/p>\n<p>Key collaborators on the studies included <a href=\"https:\/\/www.urmc.rochester.edu\/people\/112358517-harris-a-gelbard\">Harris (Handy) Gelbard<\/a>, director of the\u00a0<a href=\"https:\/\/www.urmc.rochester.edu\/neurotherapeutics-discovery.aspx\">Center for Neurotherapeutics Discovery<\/a>\u00a0at the\u00a0<a href=\"https:\/\/www.urmc.rochester.edu\/\">University of Rochester Medical Center<\/a>,\u00a0 Professor Niccol\u00f2 Terrando from the Department of Anesthesiology at the Duke University School of Medicine, and Britta Engelhardt of the Theodor Kocher Institute at the University of Bern. The research was supported by funding from the National Institutes of Health and a pre-doctoral fellowship from the International Foundation for Ethical Research to Kaihua Chen.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The cutting-edge tool demonstrates how the blood-brain barrier breaks down and how healthy brains keep it strong.<\/p>\n","protected":false},"author":1242,"featured_media":671962,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[116],"tags":[18742,18632,19182,18572],"class_list":["post-671932","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-sci-tech","tag-department-of-biomedical-engineering","tag-hajim-school-of-engineering-and-applied-sciences","tag-james-mcgrath","tag-research-finding"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Brain-on-a-chip technology reveals how sepsis and neurodegenerative diseases damage the brain<\/title>\n<meta name=\"description\" content=\"The cutting-edge tool demonstrates how the blood-brain barrier breaks down and how healthy brains keep it strong.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.rochester.edu\/newscenter\/brain-on-chip-technology-how-diseases-damage-brain-671932\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Brain-on-a-chip technology reveals how sepsis and neurodegenerative diseases damage the brain\" \/>\n<meta property=\"og:description\" content=\"The cutting-edge tool demonstrates how the blood-brain barrier breaks down and how healthy brains keep it strong.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.rochester.edu\/newscenter\/brain-on-chip-technology-how-diseases-damage-brain-671932\/\" \/>\n<meta property=\"og:site_name\" content=\"News Center\" \/>\n<meta property=\"article:published_time\" content=\"2025-10-07T16:00:04+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2025-11-19T20:21:08+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2025\/10\/fea-2024-06-26_Miller_lab_0268-1200x630.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1200\" \/>\n\t<meta property=\"og:image:height\" content=\"630\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Luke Auburn\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Luke Auburn\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"4 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/www.rochester.edu\\\/newscenter\\\/brain-on-chip-technology-how-diseases-damage-brain-671932\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.rochester.edu\\\/newscenter\\\/brain-on-chip-technology-how-diseases-damage-brain-671932\\\/\"},\"author\":{\"name\":\"Luke Auburn\",\"@id\":\"https:\\\/\\\/www.rochester.edu\\\/newscenter\\\/#\\\/schema\\\/person\\\/e928dc2863b53a89ece6d40c7992a4e1\"},\"headline\":\"Brain-on-a-chip technology reveals how sepsis and neurodegenerative diseases damage the brain\",\"datePublished\":\"2025-10-07T16:00:04+00:00\",\"dateModified\":\"2025-11-19T20:21:08+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/www.rochester.edu\\\/newscenter\\\/brain-on-chip-technology-how-diseases-damage-brain-671932\\\/\"},\"wordCount\":838,\"image\":{\"@id\":\"https:\\\/\\\/www.rochester.edu\\\/newscenter\\\/brain-on-chip-technology-how-diseases-damage-brain-671932\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.rochester.edu\\\/newscenter\\\/wp-content\\\/uploads\\\/2025\\\/10\\\/fea-2024-06-26_Miller_lab_0268.jpg\",\"keywords\":[\"Department of Biomedical Engineering\",\"Hajim School of Engineering and Applied Sciences\",\"James McGrath\",\"research finding\"],\"articleSection\":[\"Science &amp; 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