{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:13:24Z","timestamp":1778649204620,"version":"3.51.4"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"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. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Traumatic brain injury (TBI) triggers a robust neuroinflammatory response characterized by microglial activation, which propagates secondary neuronal damage and contributes to long-term neurological deficits. Rehmannioside A (REA), a principal bioactive compound from\n                      <jats:italic>Rehmannia glutinosa<\/jats:italic>\n                      , has emerged as a candidate for neuroprotection due to its anti-inflammatory properties. However, its therapeutic potential and precise mechanisms of action in TBI remain to be fully elucidated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We employed a controlled cortical impact (CCI) model in mice to mimic clinical TBI. Animals were randomized into Sham\/Veh, Sham\/REA, TBI\/Veh, and TBI\/REA (40 mg\/kg) groups. Neurological and cognitive functions were assessed using the modified Neurological Severity Score (mNSS) and Morris Water Maze (MWM). Cerebral edema was measured, and histopathological changes were evaluated by H&amp;amp;E and Nissl staining. LPS-stimulated BV2 microglial cells were used for\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments. Pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and qRT-PCR, and activation of the MAPK\/NF-\u03baB pathway was analyzed by western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      REA treatment significantly improved neurological scores, spatial learning and memory, and reduced cerebral edema and neuronal loss in TBI mice. REA suppressed microglial activation\n                      <jats:italic>in vivo<\/jats:italic>\n                      and dose-dependently inhibited LPS-induced pro-inflammatory mediators\n                      <jats:italic>in vitro<\/jats:italic>\n                      . These beneficial effects are associated with reduced phosphorylation of p65 (NF-\u03baB) and p38 (MAPK) in activated microglia\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>REA ameliorates functional deficits and neuropathology following TBI. The neuroprotective effect may involve suppression of microglia-mediated neuroinflammation via inhibition of the MAPK\/NF-\u03baB signaling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1788639","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:47:55Z","timestamp":1778647675000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Rehmannioside A alleviates neuroinflammation and cognitive impairments after traumatic brain injury by suppressing microglial activation via the MAPK\/NF-\u03baB pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Shiyu","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Immunology, Bengbu Medical College, Anhui Key Laboratory of Infection and Immunity at Bengbu Medical University","place":["Bengbu, Anhui, 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