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Yet, the immunologically privileged nature of the CNS, suggests that early manifestations - particularly mood disorders and cognitive decline - may be due to unique brain mechanisms. Neuropsychiatric symptoms in SLE can be subtle and may start early, before overt signs of inflammation in other organs. In recent years, the integration of advanced imaging tools has provided valuable insights in early events in disease pathogenesis. Intrinsic microglial activation - in the presence of an intact BBB - is an early event and may cause cognitive impairment, anxiety and depression with both activation of microglia and complement accounting for the loss of dendrites. Since NPSLE may run independently of evidence of inflammation-linked lupus manifestations (so called type 1 SLE), common symptoms in SLE such as depression, anxiety and fatigue should not be disregarded a priori as part of the fibromyalgia and not related to SLE. From a translational standpoint, early diagnosis and intervention with molecules that inhibit early damage, could improve the prognosis of NPSLE. These molecules may include cytokine inhibitors such as IL-6 at earlier stages of disease or IFN-\u03b1 later, anti-BAFF (belimumab), kinase inhibitors or oral neuroprotective agents that preserve the BBB function and\/or deactivate the microglia such as captopril, or inhibitors of complement C5a or C1q.<\/jats:p>","DOI":"10.1177\/09612033261430586","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T16:26:16Z","timestamp":1773505576000},"page":"331-340","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unique brain mechanisms in early events in SLE with diffuse neuropsychiatric disease (NPSLE): Implications for the management"],"prefix":"10.1177","volume":"35","author":[{"given":"Georgios","family":"Demirtzoglou","sequence":"first","affiliation":[{"name":"National and Kapodistrian University of Athens Medical School"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2037-9628","authenticated-orcid":false,"given":"Ariadne","family":"Damanaki","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation Academy of Athens"},{"name":"National and Kapodistrian University of Athens"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5423-5847","authenticated-orcid":false,"given":"Sofia","family":"Flouda","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens Medical School"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Grigoriou","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation Academy of Athens"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5647-6505","authenticated-orcid":false,"given":"Aggelos","family":"Banos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens Medical School"},{"name":"Biomedical Research Foundation Academy of Athens"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dionysis","family":"Nikolopoulos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens Medical School"},{"name":"Biomedical Research Foundation Academy of Athens"},{"name":"Karolinska Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9812-4671","authenticated-orcid":false,"given":"Dimitrios T","family":"Boumpas","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens Medical School"},{"name":"Biomedical Research Foundation Academy of Athens"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000655"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-015-8716-3"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22305"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.41876"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kew341"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00867-y"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.200410"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113588"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223506"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.2.1556"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603912103"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.06.003"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.1.29"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180776"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01772-6"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124002"},{"issue":"3","key":"e_1_3_4_18_2","first-page":"470","article-title":"Alterations in blood-brain barrier permeability in patients with systemic lupus erythematosus","volume":"40","author":"Chi JM","year":"2019","unstructured":"Chi JM, Mackay M, Hoang A, et al. 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