{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T05:19:05Z","timestamp":1794374345784,"version":"4.9.0"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,11,26]],"date-time":"2018-11-26T00:00:00Z","timestamp":1543190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG056770; F32AG054126"],"award-info":[{"award-number":["R01AG056770; F32AG054126"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI) is of particular concern for the aging community since there is both increased incidence of TBI and decreased functional recovery in this population. In addition, TBI is the strongest environmental risk factor for development of Alzheimer\u2019s disease and other dementia-related neurodegenerative disorders. Critical changes that affect cognition take place over time following the initial insult. Our previous work identified immune system activation as a key contributor to cognitive deficits observed in aged animals. Using a focal contusion model in the current study, we demonstrate a brain lesion and cavitation formation, as well as prolonged blood\u2013brain barrier breakdown. These changes were associated with a prolonged inflammatory response, characterized by increased microglial cell number and phagocytic activity 30 days post injury, corresponding to significant memory deficits. We next aimed to identify the injury-induced cellular and molecular changes that lead to chronic cognitive deficits in aged animals, and measured increases in complement initiation components C1q, C3, and CR3, which are known to regulate microglial\u2013synapse interactions. Specifically, we found significant accumulation of C1q on synapses within the hippocampus, which was paralleled by synapse loss 30 days post injury. We used genetic and pharmacological approaches to determine the mechanistic role of complement initiation on cognitive loss in aging animals after TBI. Notably, both genetic and pharmacological blockade of the complement pathway prevented memory deficits in aged injured animals. Thus, therapeutically targeting early components of the complement cascade represents a significant avenue for possible clinical intervention following TBI in the aging population.<\/jats:p>","DOI":"10.3390\/ijms19123753","type":"journal-article","created":{"date-parts":[[2018,11,27]],"date-time":"2018-11-27T03:31:33Z","timestamp":1543289493000},"page":"3753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":131,"title":["Traumatic Brain Injury in Aged Mice Induces Chronic Microglia Activation, Synapse Loss, and Complement-Dependent Memory Deficits"],"prefix":"10.3390","volume":"19","author":[{"given":"Karen","family":"Krukowski","sequence":"first","affiliation":[{"name":"Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA 94143, USA"},{"name":"Brain and Spinal Injury Center, University of California, San Francisco, CA 94110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA 94143, USA"},{"name":"Brain and Spinal Injury Center, University of California, San Francisco, CA 94110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA 94143, USA"},{"name":"Brain and Spinal Injury Center, University of California, San Francisco, CA 94110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brice","family":"Tiret","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA 94143, USA"},{"name":"Department of Radiology and Biomedical Imaging, University of California San Francisco, Surbeck Laboratory of Advanced Imaging, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Serena","family":"Paladini","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA 94143, USA"},{"name":"Brain and Spinal Injury Center, University of California, San Francisco, CA 94110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara-Kirstie","family":"Riparip","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA 94143, USA"},{"name":"Brain and Spinal Injury Center, University of California, San Francisco, CA 94110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam M.","family":"Chaumeil","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA 94143, USA"},{"name":"Department of Radiology and Biomedical Imaging, University of California San Francisco, Surbeck Laboratory of Advanced Imaging, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Lemere","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham &amp; Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Rosi","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA 94143, USA"},{"name":"Brain and Spinal Injury Center, University of California, San Francisco, CA 94110, USA"},{"name":"Department of Neurological Surgery, University of California, San Francisco, CA 94110, USA"},{"name":"Weill Institute for Neuroscience, University of California, San Francisco, CA 94143, USA"},{"name":"Kavli Institute of Fundamental Neuroscience, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1037\/a0018239","article-title":"Impact of age on long-term cognitive function after traumatic brain injury","volume":"24","author":"Ponsford","year":"2010","journal-title":"Neuropsychology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1037\/a0029239","article-title":"Association between cognitive performance and functional outcome following traumatic brain injury: A longitudinal multilevel examination","volume":"26","author":"Spitz","year":"2012","journal-title":"Neuropsychology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1111\/j.1532-5415.2006.00894.x","article-title":"Traumatic brain injury in older adults: Epidemiology, outcomes, and future implications","volume":"54","author":"Thompson","year":"2006","journal-title":"J. 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