{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T12:52:55Z","timestamp":1782391975415,"version":"3.54.5"},"reference-count":51,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000106","name":"Saskatchewan Health Research Foundation","doi-asserted-by":"publisher","award":["421421"],"award-info":[{"award-number":["421421"]}],"id":[{"id":"10.13039\/501100000106","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Saskatchewan, College of Medicine, Internal Fund","award":["419583"],"award-info":[{"award-number":["419583"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain injury\/concussion is a growing epidemic throughout the world. Although evidence supports association between traumatic brain injury (TBI) and disturbance in brain glucose metabolism, the underlying molecular mechanisms are not well established. Previously, we reported the release of cellular prion protein (PrPc) from the brain to circulation following TBI. The PrPc level was also found to be decreased in insulin-resistant rat brains. In the present study, we investigated the molecular link between PrPc and brain insulin resistance in a single and repeated mild TBI-induced mouse model. Mild TBI was induced in mice by dropping a weight (~95 g at 1 m high) on the right side of the head. The procedure was performed once and thrice (once daily) for single (SI) and repeated induction (RI), respectively. Micro PET\/CT imaging revealed that RI mice showed significant reduction in cortical, hippocampal and cerebellum glucose uptake compared to SI and control. Mice that received RI also showed significant motor and cognitive deficits. In co-immunoprecipitation, the interaction between PrPc, flotillin and Cbl-associated protein (CAP) observed in the control mice brains was disrupted by RI. Lipid raft isolation showed decreased levels of PrPc, flotillin and CAP in the RI mice brains. Based on observation, it is clear that PrPc has an interaction with CAP and the dislodgment of PrPc from cell membranes may lead to brain insulin resistance in a mild TBI mouse model. The present study generated a new insight into the pathogenesis of brain injury, which may result in the development of novel therapy.<\/jats:p>","DOI":"10.3390\/ijms22169005","type":"journal-article","created":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T21:47:52Z","timestamp":1629668872000},"page":"9005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Concussion\/Mild Traumatic Brain Injury (TBI) Induces Brain Insulin Resistance: A Positron Emission Tomography (PET) Scanning Study"],"prefix":"10.3390","volume":"22","author":[{"given":"Sathiya","family":"Sekar","sequence":"first","affiliation":[{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja Solomon","family":"Viswas","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajar","family":"Miranzadeh Mahabadi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elahe","family":"Alizadeh","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9388-6872","authenticated-orcid":false,"given":"Humphrey","family":"Fonge","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada"},{"name":"Department of Medical Imaging, Royal University Hospital (RUH), Saskatoon, SK S7N 0W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4527-7404","authenticated-orcid":false,"given":"Changiz","family":"Taghibiglou","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1136\/jnnp.2005.069583","article-title":"Increased cortical atrophy in patients with Alzheimer\u2032s disease and type 2 diabetes mellitus","volume":"77","author":"Biessels","year":"2006","journal-title":"J. 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