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To investigate this question, we developed and validated a scalable, closed-head controlled cortical impact model. Using this approach, we found that although concussion elicited morphological features of hyper-surveillant microglia at 1 day post-injury, they resolved by 9 days post-injury, and subconcussive impacts only produced microglial changes at 9 days post-injury. When subconcussive impacts preceded a concussive impact (i.e., preconditioned concussion), no changes in microglial morphology appeared at either 1 day or 9 days after injury. Subconcussive preconditioning also upregulated microglial genes associated with inhibiting pro-inflammatory pathways and enhancing folate metabolism. Interestingly, subconcussive preconditioning eliminated concussion-associated cognitive deficits in novel object recognition and this cognitive protection was time dependent: preconditioning impacts were only protective if delivered within 2 min of concussion and had no effect if delivered over a 48-h window. These results suggest that some types of subconcussive impacts may offer protection against subsequent concussion and mitigate changes in microglial morphology and inflammatory responses. Understanding this timing window could inform strategies for minimizing cognitive impairments in athletes exposed to repetitive head trauma.<\/jats:p>","DOI":"10.1177\/08977151261433816","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T04:33:26Z","timestamp":1774499606000},"page":"1653-1669","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Subconcussive Preconditioning Modifies Acute Microglial Response and Improves Cognitive Outcomes Post-Concussion"],"prefix":"10.1177","volume":"43","author":[{"given":"Erin D.","family":"Anderson","sequence":"first","affiliation":[{"name":"Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyulee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Pennsylvania, Philadelphia, 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