{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:39:52Z","timestamp":1791484792773,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rutgers University Foundation","award":["#21277"],"award-info":[{"award-number":["#21277"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>A disruption of the blood\u2013brain barrier (BBB) is a crucial pathophysiological change that can impact the outcome of a stroke. Ribosomal protein S6 (S6) and protein kinase B (Akt) play significant roles in early cerebral ischemia-reperfusion injury. Studies have suggested that branched-chain amino acids (BCAAs) may have neuroprotective properties for spinal cord or brain injuries. Therefore, we conducted research to investigate if leucine, one of the BCAAs, could offer neuroprotection and alter BBB disruption, along with its effects on the phosphorylation of S6 and Akt during the early phase of cerebral ischemia-reperfusion, specifically within the thrombolytic therapy time window. In rats, ten min after left middle cerebral artery occlusion (MCAO), 5 \u00b5L of 20 mM L-leucine or normal saline was injected into the left lateral ventricle. After two hours of reperfusion following one hour of MCAO, we determined the transfer coefficient (Ki) of 14C-\u03b1-aminoisobutyric acid to assess the BBB disruption, infarct size, and phosphorylation of S6 and Akt. Ischemia-reperfusion increased the Ki (+143%, p &lt; 0.001) and the intra-cerebroventricular injection of leucine lowered the Ki in the ischemic-reperfused cortex (\u221234%, p &lt; 0.001). Leucine reduced the percentage of cortical infarct (\u221242%, p &lt; 0.0001) out of the total cortical area. Ischemia-reperfusion alone significantly increased the phosphorylation of both S6 and Akt (p &lt; 0.05). However, the administration of leucine had no further effect on the phosphorylation of S6 or Akt in the ischemic-reperfused cortex. This study suggests that an acute increase in leucine levels in the brain during early ischemia-reperfusion within a few hours of stroke may offer neuroprotection, possibly due to reduced BBB disruption being one of the major contributing factors. Leucine did not further increase the already elevated phosphorylation of S6 or Akt by ischemia-reperfusion under the current experimental conditions. Our data warrant further studies on the effects of leucine on neuronal survival and its mechanisms in the later stages of cerebral ischemia-reperfusion.<\/jats:p>","DOI":"10.3390\/brainsci13101372","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T08:55:01Z","timestamp":1695718501000},"page":"1372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Leucine Reduced Blood\u2013Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0374-8447","authenticated-orcid":false,"given":"Oak Z.","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, Suite 3100, New Brunswick, NJ 08901-1977, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, Suite 3100, New Brunswick, NJ 08901-1977, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jedrick","family":"Magsino","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Rutgers Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854-8021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey R.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854-8021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.cell.2015.10.067","article-title":"Establishment and Dysfunction of the Blood-Brain Barrier","volume":"163","author":"Zhao","year":"2015","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1097\/WNR.0000000000001357","article-title":"Calcium Signaling in Brain Microvascular Endothelial Cells and Its Roles in the Function of the Blood-Brain Barrier","volume":"30","author":"Ma","year":"2019","journal-title":"Neuroreport"},{"key":"ref_3","first-page":"699","article-title":"Effects of Blockade of Ionotropic Glutamate Receptors on Blood-Brain Barrier Disruption in Focal Cerebral Ischemia","volume":"31","author":"Liu","year":"2010","journal-title":"Neurol. 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