An Experimental Study of the Neuroprotective Effect of Sodium–Glucose Cotransporter Type 2 Inhibitors

Abstract Sodium–glucose cotransporter type 2 inhibitors (SGLT2i) have proven cardioprotective properties, which makes this class of drugs one of the priorities in the treatment of patients with type 2 diabetes mellitus (DM2). Ischemic stroke and chronic cerebral dyscirculation occur with high frequency in DM2, thus actualizing a study of SGLT2i neurotropic properties. The aim of our study was to evaluate and compare the neuroprotective effects of the highly selective SGLT2i empagliflozin (EMPA) and low-selective SGLT2i canagliflozin (CANA) on the rat model of acute cerebral ischemia, as well as investigate the probable mechanism of these effects on the brain. At the first stage, EMPA and CANA were administered to Wistar rats without DM2 for 7 days prior to transient focal 30-min cerebral ischemia modeling. After 48 h of reperfusion, neurological deficit was assessed by Garcia scores, and brain sections were then incubated in a triphenyltetrazolium chloride solution to evaluate the brain damage volume. The latter did not differ in EMPA and CANA groups and was significantly smaller compared to the control group of untreated rats. At the same time, neither EMPA nor CANA had a significant effect on neurological deficit. At the second stage, we modeled DM2 (high-fat diet and streptozotocin + nicotinamide), and 4 weeks later, 8-week EMPA and CANA therapy was initiated. After the end of therapy, brain tissue was studied immunohistochemically. DM2 development was accompanied by an increase in the number of microgliocytes in the hippocampal CA1 area; the therapy with EMPA, but not CANA, led to a decrease in the number of activated microgliocytes. Thus, the highly selective SGLT-2i EMPA and low-selective SGLT-2i CANA exert a similar infarct-limiting effect when applied for 7 days prior to ischemia modeling in Wistar rats without DM2. The neuroprotective effect of EMPA in DM2 may in part be due to a decrease in microglial activation..

Medienart:	E-Artikel

Erscheinungsjahr:	2022
Erschienen:	2022

Enthalten in:	Zur Gesamtaufnahme - volume:58
Enthalten in:	Journal of evolutionary biochemistry and physiology - 58(2022), 5 vom: Sept., Seite 1540-1553

Sprache:	Englisch

Beteiligte Personen:	Simanenkova, A. V. [VerfasserIn] Fuks, О. S. [VerfasserIn] Timkina, N. V. [VerfasserIn] Karonova, T. L. [VerfasserIn] Tsyba, D. L. [VerfasserIn] Kirik, О. V. [VerfasserIn] Korzhevskii, D. E. [VerfasserIn] Vlasov, T. D. [VerfasserIn]

Links:	Volltext [lizenzpflichtig]

BKL:	35.70$jBiochemie: Allgemeines 42.18$jPhysiologie der Enzyme, Hormone, Sekrete

Anmerkungen:	© Pleiades Publishing, Ltd. 2022

doi:	10.1134/S0022093022050234

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	OLC213256700X