Endocrine Abstracts

Background and aims: The most outstanding cardioprotective potential has been demonstrated for GLP-1 receptor agonists (GLP-1RA) and SGLT-2 inhibitors (SGLT-2i). But only long-acting GLP-1RA dulaglutide (DULA) and semaglutide decrease stroke incidence, while data concerning the influence of any drug on stroke severity are lack. At the same time, ischemic stroke remains one of the leading causes of death in type 2 diabetes mellitus (DM2). The aim of our study was to investigate neuroprotective actions of liraglutide (LIRA), DULA and empagliflozin (EMPA), in comparison with metformin (MET) in acute rat brain ischemia. We have chosen two GLP-1RA with different action duration to evaluate drug- or class-effect.

Materials and methods: male Wistar rats 200-255 g were treated for 7 days with LIRA 1 mg/kg s.c. once daily (“LIRA”, n=12), DULA 0.12 mg/kg s.c. every 72 h (“DULA”, n=10), EMPA 2 mg/kg per os once daily (“EMPA”, n=9), MET 200 mg/kg kg per os once daily (“MET”, n=8) or 0.9% NaCl s.c. once daily (“Control”, n=12). Then all animals were subjected to 30-min filament middle cerebral artery occlusion (MCAO). 48 h after MCAO neurological deficit was evaluated by Garcia scores – healthy animals have 18 points, maximal neurological deficit is characterized by 3 points. Then rats were euthanized, brain slices were incubated with 1% 2,3,5-triphenyltetrazolium chloride for necrosis measurement. Blood glucose level (BGL) was studied every second day.

Results: Brain infarct volume was significantly smaller in “LIRA” and “DULA” (5.50(3.97;5.50)% and 6.65(4.1;11.0)%) comparing with “Control” (16.56(13.33;24.65)% of total brain volume). Stroke volume in “EMPA” (4.91(2.67;14.49)%) was also smaller than in “Control”. There was no difference among “LIRA”, “DULA” and “EMPA” groups. Treatment with MET also led to brain damage volume decrease (8.67(5.39;30.07)%), comparing with control, but it was larger than in other treatment groups. Rats in groups “LIRA” and “DULA” had less prominent neurological deficit and more points according to Garcia score (14.0(11.5;15.5) and 13.5(8.5;15.0)) comparing with “Control” (12.0(9.0;14.0)), with no difference between LIRA and DULA. Neither EMPA (12.0(9.5;14.0)), nor MET (12.0(6.5;12.5) points) diminished neurological deficit, comparing with “Control”. BGL was normal in all groups.

Conclusions: GLP-1RA, SGLT-2i and MET are neuroprotective in rat transient brain ischemia and this effect is not connected with glucose metabolism. Infart-limiting effect of LIRA, DULA and EMPA is similar and is more prominent than that of MET. Only GLP-1RA diminish neurological deficit. Neuroprotective property of GLP-1RA with different action duration is similar, being most probably a class-effect.