{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:58:24Z","timestamp":1790618304923,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Pyrroloquinoline quinone (PQQ) was reported to be neuroprotective after experimental traumatic brain injury (TBI), but its mechanisms remain undefined. We tested whether PQQ protects against TBI in mice and identified the associated pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male C57BL\/6 mice received intraperitoneal PQQ (6.25, 12.5 or 25\u2009mg\/kg) immediately after controlled cortical impact. Mortality, modified neurological severity score (mNSS) and beam balance were followed to day 14; histopathology, immunofluorescence, western blot, ELISA and ATP assays were performed on day 3. Transcriptomics, metabolomics, network pharmacology and docking were integrated to identify candidate mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PQQ reduced mortality (lowest at 12.5\u2009mg\/kg) and dose\u2010dependently improved neurological deficits, neuronal apoptosis, brain edema, pro\u2010inflammatory cytokines, and oxidative stress; the mNSS and beam balance benefits persisted to day 14. At 12.5\u2009mg\/kg, multi\u2010omics and network pharmacology identified arginine biosynthesis, mediated by argininosuccinate synthetase 1 (ASS1) and carbamoyl phosphate synthetase 1 (CPS1), as the top\u2010ranked pathway suppressed by PQQ; docking predicted binding of PQQ to both enzymes, suggesting putative targets pending validation. PQQ concurrently restored PTEN\u2010induced kinase 1 (PINK1)\/Parkin\u2010mediated mitophagy and ATP production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PQQ attenuates secondary injury after TBI in male mice, in association with increased markers of PINK1\/Parkin\u2010mediated mitophagy initiation and suppressed ASS1\/CPS1\u2010driven arginine biosynthesis, identifying a candidate dual\u2010axis mechanism and nominating the mitophagy\u2010arginine axis as a target for neuroprotection in TBI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71146","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:11:28Z","timestamp":1789020688000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pyrroloquinoline Quinone Attenuates Traumatic Brain Injury\u2010Induced Secondary Damage by Activating PINK1\/Parkin\u2010Mediated Mitophagy and Suppressing ASS1\/CPS1\u2010Driven Arginine Biosynthesis"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0745-6249","authenticated-orcid":false,"given":"Yanan","family":"He","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The First Medical Center of Chinese PLA General Hospital  Beijing China"},{"name":"Beijing Key Laboratory of Perioperative Multimodal Digital Intelligence\u2010Integrated Diagnosis and Treatment  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The First Medical Center of Chinese PLA General Hospital  Beijing China"},{"name":"Beijing Key Laboratory of Perioperative Multimodal Digital Intelligence\u2010Integrated Diagnosis and Treatment  Beijing 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