{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:08:22Z","timestamp":1784268502110,"version":"3.55.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ischemic stroke is the second leading cause of death worldwide, characterized by high mortality and a narrow therapeutic window for thrombolysis. Gut microbiota dysbiosis and gliosis following ischemic stroke are key drivers of post\u2010stroke neurological impairment. Sodium oligomannate (GV\u2010971) is a low\u2010molecular\u2010weight acidic oligosaccharide that targets the gut\u2013brain axis. It alleviates gliosis and improves cognitive dysfunction by remodeling gut microbiota in Alzheimer\u2019s disease. However, it is still unknown whether GV\u2010971 has pharmacological activity against ischemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we explore the efficacy of GV\u2010971 on infarct volume, gliosis, blood\u2010brain barrier integrity, gut microbiota composition, and post\u2010stroke cognitive impairment (PSCI) using a middle cerebral artery occlusion\/reperfusion (MCAO\/R) model in male Sprague\u2010Dawley rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Administer medication before surgery for 4 consecutive days and once after surgery, after stroke 24\u2010hour triphenyltetrazolium chloride (TTC) staining revealed that 0.3 mg\/kg GV\u2010971 significantly reduced infarct volume in ischemic brain tissue from 37.81\u00b12.391% to 13.30\u00b14.801% and neurological impairment score of GV\u2010971 treatment significantly decreased from 11.50\u00b10.54 to 7.29\u00b11.47. After stroke 24\u2010hour immunofluorescence analysis of glial activation confirmed that GV\u2010971 significantly reduced central inflammatory responses. Western blot combined with Evans blue staining collectively demonstrated that after stroke 24\u2010hour, GV\u2010971 exerts a significant protective effect on the blood\u2010brain barrier. In the gut, GV\u2010971 reversed microbial dysbiosis, as revealed by shotgun metagenomics, enhanced intestinal barrier integrity, and suppressed colonic inflammation. Antibiotic depletion abolished GV\u2010971's neuroprotective effect, while fecal microbiota transplantation from GV\u2010971\u2010treated donors restored protection, supporting a microbiota\u2010dependent contribution. Furthermore, GV\u2010971\u2010treated rats subjected to MCAO\/R exhibited significant improvements in motor and cognitive function. For example, on day 35, Y\u2010maze test results indicated that GV\u2010971 administered either before MCAO\/R (pre\u2010treatment) or during the perioperative period (co\u2010treatment) increased spontaneous alternation rate from 60.95\u00b14.91% to 85.60\u00b16.32% and 85.64\u00b15.027%. On day 32, novel object recognition assay results indicated that GV\u2010971 treatment increased new\u2010object exploration from 0.2039\u00b10.03752 to 0.3991\u00b10.1122 (pre\u2010treatment) and 0.5066\u00b10.06982 (co\u2010treatment). On day 42, Barnes maze test results indicated that GV\u2010971 treatment reduced the time required to locate the target hole from 76.45\u00b117.41s to 31.03\u00b120.75\u2009s and 33.37\u00b119.30\u2009s for pre\u2010 and co\u2010treatment, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Taken together, GV\u2010971 demonstrated neuroprotective potential in experimental ischemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1880590","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:43:34Z","timestamp":1784267014000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sodium oligomannate reduces cerebral infarction and improves neurological function through microbiota remodeling in MCAO\/R 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