{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:30:01Z","timestamp":1789047001950,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":["Brain and Behavior"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Approximately 30% of epilepsy patients develop pharmacoresistant epilepsy (PRE), characterized by persistent seizures refractory to antiseizure medications (ASMs). While neuroinflammation is implicated in both epileptogenesis and treatment failure, its precise temporal contribution remains unclear. This study aimed to delineate the distinct roles of acute versus chronic neuroinflammation in seizure susceptibility and the maintenance of drug resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Sprague\u2010Dawley rats received acute inflammatory priming via systemic (intraperitoneal) or intracranial (hippocampal) lipopolysaccharide (LPS) administration prior to lithium\u2010pilocarpine\u2010induced status epilepticus (SE). Rats were subsequently classified as PRE or pharmacosensitive epilepsy (PSE) based on their response to two sequentially administered ASMs. Outcomes were assessed using video\u2010EEG monitoring, hippocampal cytokine profiling (IL\u20106 and TNF\u2010\u03b1), histopathological analysis of neuronal damage, and peripheral inflammatory markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Acute inflammatory priming significantly lowered the threshold for SE induction (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05); however, it did not increase the proportion of PRE (\n                      <jats:italic>P<\/jats:italic>\n                      &gt; 0.05). In contrast, established PRE was characterized by sustained hippocampal neuroinflammation, with markedly elevated IL\u20106 and TNF\u2010\u03b1 levels compared to PSE and control groups, alongside severe neuronal loss.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings reveal a temporal dissociation in the roles of neuroinflammation: acute inflammation acts as a potent initiator of epileptogenesis, whereas chronic, sustained inflammation coincides with the drug\u2010resistant phenotype. This study refines the prevailing view of neuroinflammation from a static pathogenic factor to a dynamic, phase\u2010dependent modulator, supporting the rationale for stage\u2010targeted strategies in PRE. Notably, putative mechanisms linking inflammation to resistance, such as impaired efferocytosis, warrant future experimental validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71657","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:10:44Z","timestamp":1786954244000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling the Inflammatory Enigma: Is Neuroinflammation a Culprit or Consequence in Pharmacoresistant Epilepsy?"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1090-1545","authenticated-orcid":false,"given":"Xianmei","family":"Wang","sequence":"first","affiliation":[{"name":"Emergency Department the Affiliated Hospital of Guizhou Medical University  Guiyang City Guizhou Province China"},{"name":"School of Nursing Guizhou Medical University  Guiyang City Guizhou Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education  Guiyang City Guizhou Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Shi","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang Guizhou Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Nursing Guizhou Medical University  Guiyang City Guizhou Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Likun","family":"Wang","sequence":"additional","affiliation":[{"name":"Emergency Department the Affiliated Hospital of Guizhou Medical University  Guiyang City Guizhou Province 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