{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T10:58:02Z","timestamp":1769857082517,"version":"3.49.0"},"reference-count":24,"publisher":"Endocrinology Research Centre","issue":"4","license":[{"start":{"date-parts":[[2024,9,15]],"date-time":"2024-09-15T00:00:00Z","timestamp":1726358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.probl-endojournals.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":["www.probl-endojournals.ru"],"crossmark-restriction":true},"short-container-title":["Probl Endokrinol (Mosk)"],"abstract":"<jats:p><jats:bold>BACKGROUND<\/jats:bold>: Chronic brain dyscirculation is one of the frequent type 2 diabetes mellitus (DM) complications and leads to patients\u2019 disability. Sodium-glucose co-transporter type 2 inhibitors (SGLT-2i) have been proven to have advantages for cardiovascular system, but their effect on the central nervous system (CNS) has not been studied enough.<\/jats:p><jats:p><jats:bold>AIM<\/jats:bold>: To study empagliflozin effect on CNS damage functional and laboratory parameters in patients with type 2 DM and, under experimental conditions, to investigate the mechanisms of the drug neurotropic effect.<\/jats:p><jats:p><jats:bold>MATERIALS AND METHODS<\/jats:bold>: The clinical part of the study included patients with type 2 DM on metformin monotherapy (n=39). Patients with a target glycated hemoglobin level formed the \u201cMET\u201d group (n=19), in patients with a non-target glycated hemoglobin level empagliflozin was co-administered for the following 6 months (the \u201cMET+EMPA\u201d group, n=20). Healthy volunteers comprised the control group (n=16). The cognitive status and neuron-specific enolase (NSE) and neurofilament light chains (NLC) concentration were studied. DM was modeled in rats, thereafter the rats were treated with empagliflozin for 8 weeks. Microglia activation was assessed using anti-Iba-1 antibodies and morphological changes in neurons when stained by the Nissl method.<\/jats:p><jats:p><jats:bold>RESULTS:<\/jats:bold> Both in the \u201cMET+EMPA\u201d and the \u201cMET\u201d groups cognitive deficits were observed, according to the Montreal Cognitive Assessment (MOCA) (24.0 (23.0; 27.0) and 25.0 (21.0; 27.0) points) and the Mini-Mental State Examination (MMSE) (23.75 (23.0; 27.0) and 25.0 (21.0; 27.0) points). Empagliflozin therapy led to the cognitive status normalization after 6 months (26.5 (24.0; 27.0) points according to the MOCA scale and 27.5 (24.0; 28.0) points according to the MMSE). Initially, all patients had a significant increase of NSE (3.60 (2.66; 3.76) ng\/ml in the \u201cMET\u201d group, 3.22 (2.94; 3.54) ng\/ml in the \u201cMET+EMPA\u00bb group, 2.72 (2.13; 2.72) ng\/ml in the \u00abControl\u00bb group) and NLC (4.50 (3.31; 5.56) ng\/ml in the \u00abMET\u00bb group, 5, 25 (3.75; 6.25) ng\/ml in the \u00abMET+EMPA\u00bb group comparing with 3.50 (2.25; 3.50) ng\/ml in the \u00abControl\u00bb group). Empagliflozin therapy led to a significant decrease in NLC already after 3 months (3.80 (3.25; 3.87) ng\/ml), without significant influence on the NSE level. In the experiment, DM was characterized by an increased number of activated microgliocytes and destructured neurons and a decreased number of neurons with a normal structure. Empagliflozin therapy was accompanied by a decrease in the number of immunopositive microgliocytes in the CA1 zone of the hippocampus and an increase in the number of structured neurons.<\/jats:p><jats:p><jats:bold>CONCLUSION:<\/jats:bold> Type 2 diabetes mellitus is characterized by functional and biochemical changes in the central nervous system even under satisfactory glycemic control. Therapy with empagliflozin has a neuroprotective effect, manifested in an improvement in cognitive status and a decrease in NLC level. Empagliflozin reduces neuronal damage and abnormal microglial activation.<\/jats:p>","DOI":"10.14341\/probl13336","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T16:42:57Z","timestamp":1726591377000},"page":"44-56","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":4,"title":["Highly selective sodium-glucose co-transporter type 2 inhibitor empagliflozin as means of brain protection in conditions of chronic brain dyscirculation"],"prefix":"10.14341","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3300-1280","authenticated-orcid":true,"given":"A. V.","family":"Simanenkova","sequence":"first","affiliation":[{"name":"Almazov National Medical Research Centre; Pavlov First Saint-Petersburg State medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0112-5027","authenticated-orcid":true,"given":"O. S.","family":"Fuks","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9836-5427","authenticated-orcid":true,"given":"N. V.","family":"Timkina","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre; Pavlov First Saint-Petersburg State medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0048-2981","authenticated-orcid":true,"given":"D. A.","family":"Sufieva","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6113-3948","authenticated-orcid":true,"given":"O. V.","family":"Kirik","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2456-8165","authenticated-orcid":true,"given":"D. E.","family":"Korzhevskii","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6951-7599","authenticated-orcid":true,"given":"T. D.","family":"Vlasov","sequence":"additional","affiliation":[{"name":"Pavlov First Saint-Petersburg State medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-0123","authenticated-orcid":true,"given":"T. L.","family":"Karonova","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre; Pavlov First Saint-Petersburg State medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5458","published-online":{"date-parts":[[2024,9,15]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Dedov II, Shestakova MV, Vikulova OK, et al. Epidemiological characteristics of diabetes mellitus in the Russian Federation: clinical and statistical analysis according to the Federal diabetes register data of 01.01.2021. Diabetes mellitus. 2021;24(3):204-221 (in Russ.). doi: https:\/\/doi.org\/10.14341\/DM12759","DOI":"10.14341\/DM12759"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Mosenzon O, Cheng AY, Rabinstein AA, et al. Diabetes and Stroke: What Are the Connections? 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