{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:15:13Z","timestamp":1791573313020,"version":"4.3.4"},"reference-count":78,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation (NRF) of Korea","doi-asserted-by":"crossref","award":["NRF-2023R1A2C2006414"],"award-info":[{"award-number":["NRF-2023R1A2C2006414"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation (NRF) of Korea","doi-asserted-by":"crossref","award":["NRF-2020R1A2C1101082"],"award-info":[{"award-number":["NRF-2020R1A2C1101082"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Evidence on the therapeutic use of nanoparticles for traumatic brain injury (TBI) remains limited. This study aimed to evaluate the neuroprotective potential of atorvastatin-loaded polyethylene glycol (PEG)-conjugated liposomes (LipoStatin) in a mouse model of repetitive TBI. TBI was induced using five controlled head impacts with a 120 g weight at 12-h intervals. Mice were randomly assigned to Sham, Control (saline-treated), Statin (free atorvastatin), Liposome (empty PEGylated liposomes without atorvastatin), and LipoStatin (atorvastatin-loaded PEGylated liposome) groups. LipoStatin (10 mg\/kg\/day) was intravenously administered for 5 days post-injury. Neurological function was evaluated using the neurological severity score (NSS), while blood\u2013brain barrier (BBB) integrity and neuroinflammation were assessed on day 5, and cellular apoptosis on day 12. LipoStatin-treated mice exhibited the lowest NSSs. IVIS\u00ae imaging indicated significantly attenuated BBB disruption (p &lt; 0.001), and Western blot analysis revealed restored caveolin-1 protein levels (p &lt; 0.01), which are associated with BBB integrity. TNF-\u03b1 levels were reduced considerably in the LipoStatin group compared to both the Control (p &lt; 0.001) and Statin (p &lt; 0.05) groups. Immunofluorescence showed reduced co-localization of caspase-3 with PDGFR-\u03b2 and GFAP, indicating decreased pericyte and astrocyte apoptosis. These findings suggest that LipoStatin may confer neuroprotection in TBI by stabilizing BBB integrity, reducing inflammation, and mitigating cell death, supporting its potential as an improved nanocarrier-based therapeutic approach.<\/jats:p>","DOI":"10.3390\/ijms262412176","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:32:03Z","timestamp":1766068323000},"page":"12176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Preclinical Evaluation of Atorvastatin-Loaded PEGylated Liposomes in a Mouse Model of Traumatic Brain Injury"],"prefix":"10.3390","volume":"26","author":[{"given":"Eun-Sol","family":"Hwang","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School and Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4077-7722","authenticated-orcid":false,"given":"Ja-Hae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Chonnam National University Medical School and Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hye","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Chonnam National University Medical School and Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0252-7119","authenticated-orcid":false,"given":"Raveena","family":"Nagareddy","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School and Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6096-3130","authenticated-orcid":false,"given":"Yong-Yeon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Radiology, Chonnam National University Medical School and Hwasun Hospital, Hwasun 58128, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8851-2104","authenticated-orcid":false,"given":"Kang-Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School and Hospital, Gwangju 61469, Republic of Korea"},{"name":"Department of Neurology, Chonnam National University Medical School and Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e075049","DOI":"10.1136\/bmjopen-2023-075049","article-title":"Global, regional and national burden of traumatic brain injury and spinal cord injury, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"13","author":"Guan","year":"2023","journal-title":"BMJ Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/S1474-4422(22)00309-X","article-title":"Traumatic brain injury: Progress and challenges in prevention, clinical care, and research","volume":"21","author":"Maas","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"149040","DOI":"10.1016\/j.brainres.2024.149040","article-title":"Repetitive mild traumatic brain injury impairs norepinephrine system function and psychostimulant responsivity","volume":"1839","author":"Horvat","year":"2024","journal-title":"Brain Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"0085","DOI":"10.34133\/bmr.0085","article-title":"Hydrogel in the treatment of traumatic brain injury","volume":"28","author":"Li","year":"2024","journal-title":"Biomater. 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