{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:01:49Z","timestamp":1777942909048,"version":"3.51.4"},"reference-count":42,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T00:00:00Z","timestamp":1710547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82104444"],"award-info":[{"award-number":["82104444"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the National Science and Technology Major Projects","award":["2018ZX09737-009"],"award-info":[{"award-number":["2018ZX09737-009"]}]},{"name":"the Fundamental Research Funds for the Central Public Welfare Research Institutes","award":["ZZ15-YQ-008"],"award-info":[{"award-number":["ZZ15-YQ-008"]}]},{"name":"Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences","award":["CI2021A04617"],"award-info":[{"award-number":["CI2021A04617"]}]},{"name":"Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences","award":["CI2021A01304"],"award-info":[{"award-number":["CI2021A01304"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Neurorehabil Neural Repair"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Yi-Qi-Tong-Luo Granules (YQTLs) is a natural compound of Traditional Chinese Medicine authorized by China Food and Drug Administration (CFDA). These granules are employed in the convalescent stage of cerebral infarction and render notable clinical efficacy. This study aims to uncover the underlying mechanisms of YQTLs on remyelination after cerebral ischemia injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We established cerebral ischemia model in rats using microsphere-induced multiple cerebral infarction (MCI). We evaluated the pharmacological effects of YQTLs on MCI rats, through Morri\u2019s water maze test, open field test, hematoxylin and eosin staining, and glycine silver immersion. We employed liquid chromatography mass spectrometry metabolomics to identify differential metabolites. Enzyme-linked immunosorbent assay was utilized to measure the release of neurotrophins, while immunofluorescence staining was used to assess oligodendrocyte precursor cells differences and myelin regeneration. We used Western blotting to validate the protein expression of remyelination-associated signaling pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>YQTLs significantly improves cognitive function following cerebral ischemia injury. Pathological tissue staining revealed that YQTLs administration inhibits neuronal denaturation and neurofibrillary tangles. We identified 141 differential metabolites among the sham, MCI, and YQTLs-treated MCI groups. Among these metabolites, neurotransmitters were identified, and notably, gamma-aminobutyric acid (GABA) showed marked improvement in the YQTLs group. The induction of neurotrophins, such as brain-derived neurotrophic factor (BDNF) and PDGFAA, upregulation of olig2 and MBP expression, and promotion of remyelination were evident in YQTLs-treated MCI groups. Gamma-aminobutyric acid B receptors (GABABR), pERK\/extracellular regulated MAP kinase, pAKT\/protein kinase B, and pCREB\/cAMP response element-binding were upregulated following YQTLs treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>YQTLs enhance the binding of GABA to GABABR, thereby activating the pCREB\/BDNF signaling pathway, which in turn increases the expression of downstream myelin-associated proteins and promotes remyelination and cognitive function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15459683241238733","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T05:25:05Z","timestamp":1710566705000},"page":"350-363","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolomics-Based Effects of a Natural Product on Remyelination After Cerebral Ischemia Injury Via GABABR\u2013pCREB\u2013BDNF Pathway"],"prefix":"10.1177","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5004-7099","authenticated-orcid":false,"given":"Xiaodi","family":"Fan","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China"},{"name":"Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhan","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China"},{"name":"Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenting","family":"Song","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China"},{"name":"Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjiang","family":"Yao","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China"},{"name":"Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangrui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China"},{"name":"Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Fourth Military Medical University, Xi\u2019an, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yehao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China"},{"name":"Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxun","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China"},{"name":"Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, 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