SGLT-2 Inhibitors' and GLP-1 Receptor Agonists' Influence on Neuronal and Glial Damage in Experimental Stroke.

SGLT-2 inhibitors (SGLT-2i) and GLP-1 receptor agonists (GLP-1RA) have demonstrated nephro- and cardioprotective effects, but their neuroprotective properties, especially concerning stroke severity, and mechanisms are not unambiguous. We aimed to study the influence of SGLT-2i with different selectivity and GLP-1RA on brain damage volume and neurological status in non-diabetic and diabetic rats and to investigate the underlying mechanisms. Non-diabetic rats were divided into five groups (n = 10 each) and received empagliflozin, canagliflozin, or dulaglutide as study drugs and metformin as comparison drug.

[Highly selective sodium-glucose co-transporter type 2 inhibitor empagliflozin as means of brain protection in conditions of chronic brain dyscirculation].

Background: Chronic brain dyscirculation is one of the frequent type 2 diabetes mellitus (DM) complications and leads to patients' 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.

Aim: 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.

Microglia Involvement into Acute and Chronic Brain Damage in Diabetic Rats: Impact of GLP-1RA and SGLT-2i.

Background: Acute and chronic brain damage in type 2 diabetes mellitus (DM) determines the need to investigate the neuroprotective potential of glucose-lowering drugs. The purpose was to directly compare the neuroprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with different duration of action and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in type 2 diabetic rats with and without stroke.

Methods: DM was modelled using high-fat diet and nicotinamide+streptozotocin protocol.

C adduct with L-arginine as a promising nanomaterial for treating cerebral ischemic stroke.

The work aimed to investigate the biocompatibility and biological activity of the water-soluble fullerene adduct C-Arg. It was found that the material is haemocompatible, is not cyto- and genotoxic, possesses pronounced antioxidant activity. Additionally, this paper outlines the direction of application of water-soluble fullerene adducts in the creation of neuroprotectors.

[Epithelial protective therapy in comorbid diseases. Practical Guidelines for Physicians].

This document was produced with the support of the National Medical Association for the Study of Comorbidities (NASС). In 2021 the first multidisciplinary National Consensus on the pathophysiological and clinical aspects of Increased Epithelial Permeability Syndrome was published. The proposed guidelines are developed on the basis of this Consensus, by the same team of experts.

Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance.

Impaired glucose tolerance (IGT) increases cardiovascular risk and can enlarge myocardial infarction (MI) incidence and severity. There is lack of information about cardioprotective potential of glucose-lowering drugs in IGT. We aimed to evaluate the sustainability of myocardium to ischemia-reperfusion injury in diabetic and IGT rats and to study cardioprotective action of metformin and liraglutide.

Influence of the cumulative effect of zoledronic acid on periodontal microcirculation in rats.

Purpose: To evaluate the effect of repeated administration of zoledronic acid (ZA) on the development and severity of osteonecrosis of the jaws.

Methods: In the experiment, 36 rats were used, which were divided into 4 groups: group 1 was injected with saline for 6 weeks, group 2 was injected with ZA once, group 3 was injected zoledronic acid for 3 weeks once a week, group 4 was injected with ZA for 6 weeks once a week. While taking medications, the tooth was removed.

Disorders of microcirculation in the mechanism of bisphosphonate osteonecrosis: preliminary study in rats.

We investigated the possibilities of angioprotection and the reduction of osteonecrosis in rats that had been given bisphosphonates. In our experiment, 27 rats were divided into three groups: Group 1 was injected with saline; Group 2 was given zoledronic acid for six weeks; and Group 3 was given zoledronic acid for six weeks, with added doses of sulodexide after three weeks. After that we constructed a model of how the teeth should be extracted.

Neuroprotective effect of glucagon-like peptide-1 receptor agonist is independent of glycaemia normalization in type two diabetic rats.

Objective: Stroke is a severe complication of type 2 diabetes mellitus. Glucagon-like peptide-1 receptor agonists have been shown to have a neuroprotective effect in experimental diabetes. The aim of this study was to determine if their neuroprotective effect is an independent property of the drug independent of glycaemic control.

[Preclinical studies of drugs on animal stroke models].

Preclinical studies are studies using experimental models of stroke in animals as well as on neurons, cell neuronal cultures and surviving brain slices. They directed both towards testing the efficacy and evaluation of the mechanisms of action of drugs, and the study of the mechanisms of ischemic damage to search for new targets for stroke treatment. This article shows the basic principles of the organization and planning of animal models of ischemic stroke.

[The administration of neurocytoprotectors in a rat model of experimental spinal cord ischemia].

Aim: To study an effect of cortexin on functional recovery and morphology of the spinal cord of rats with spinal cord ischemia.

Material And Methods: Spinal cord ischemia was achieved by ligation of the infrarenal abdominal aorta in 16 rats stratified into two equal groups: the ligation of infrarenal aorta was performed in the control group, aorta ligation was performed also in the experimental group with preliminary intraperitoneally administration of cortexin in a dose of 0.15 mg/kg 30 min before procedure.

Experimental model of osteonecrosis of the jaw in rats treated with zoledronic acid.

We have examined the development of medication-related osteonecrosis of the jaws (MRONJ) in rats with no previous accumulation of zoledronic acid in the mandible. Ten male Wistar rats (weight 350-400g) were anaesthetised with chloral hydrate 450mg/kg intraperitoneally and the first and second mandibular molars on the left side were extracted. The five experimental rats were given six injections of zoledronic acid 0.

Remote vs. local ischaemic preconditioning in the rat heart: infarct limitation, suppression of ischaemic arrhythmia and the role of reactive oxygen species.

The unmet clinical need for myocardial salvage during ischaemia-reperfusion injury requires the development of new techniques for myocardial protection. In this study the protective effect of different local ischaemic preconditioning (LIPC) and remote ischaemic preconditioning (RIPC) protocols was compared in the rat model of myocardial ischaemia-reperfusion, using infarct size and ischaemic tachyarrhythmias as end-points. In addition, the hypothesis that there is involvement of reactive oxygen species (ROS) in the protective signalling by RIPC was tested, again in comparison with LIPC.

APPLICATION OF GRAFTSKIN TO ACCELERATE HEALING OF ULCERS IN DIABETIC FOOT SYNDROME.

Diabetic foot syndrome (DFS) is one of the severe and more frequent complications of diabetes. It is characterized by occurrence of chronic purulent necrotic processes (trophic ulcers) on the foot with damage of skin, soft tissues and osteoarticular system due to pathological changes in the peripheral nervous system (diabetic neuropathy) and vascular system (diabetic angiopathy). This study aimed to evaluate the possibility of accelerating of wound healing in DFS by using the dermal equivalent (graftskin) and determine the safety of the method, factors and indications for its application.

[Preconditioning by physical factors: role of active forms of oxygen].

In the review mechanisms of protective action of a hyperthermia, light and low-intensity ultrasonic radiation are considered. These physical factors don't cause oxygen starvation, however promote the increase of organ's tolerance to an ischemia/hypoxia. On materials of original articles the analysis of preconditioning mechanisms cause by high temperatures, low-intensive ultrasonic and laser irradiation was carried out at ischemia.

Neuroprotective activity of creatylglycine ethyl ester fumarate.

Background: We have recently shown neuroprotective activity of the creatine amides in the focal cerebral ischemia in rats on the 280 mg/kg administration. In the present study, neuroprotective properties of creatylglycine ethyl ester fumarate (CrGEt) in rats with focal cerebral ischemia were explored in a wide dosage range (30-280 mg/kg, intravenous and intragastric).

Methods: Focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO).

Preservation of the donor heart: from basic science to clinical studies.

The methods of donor heart preservation are aimed at minimizing graft dysfunction caused by ischaemia-reperfusion injury (IRI) which inevitably occurs during the ex vivo transport interval. At present, the standard technique of heart preservation is cardiac arrest followed by static cold storage in a crystalloid heart preservation solution (HPS). This technique ensures an acceptable level of heart protection against IRI for <6 h.

Neurotherapeutic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats.

Recombinant 70 kDa heat shock protein (Hsp70) is an antiapoptotic protein that has a cell protective activity in stress stimuli and thus could be a useful therapeutic agent in the management of patients with acute ischemic stroke. The neuroprotective and neurotherapeutic activity of recombinant Hsp70 was explored in a model of experimental stroke in rats. Ischemia was produced by the occlusion of the middle cerebral artery for 45 minutes.

Neuroprotective effects of erythropoietin in focal brain ischemia in rats.

Neuroprotective effect of erythropoietin administered before ischemia has been previously demonstrated. The efficiency of erythropoietin administration after ischemia was not studied, though in case of success these protocols would be applied in clinical neurology. In our experiments on the model of transitory focal ischemia, erythropoietin was injected intraperitoneally during the early and delayed postischemic period (3 and 12 h).

Evidence of active regulation of cerebral venous tone in individuals undergoing embolization of brain arteriovenous malformations.

Cerebral venous drainage is generally believed to be regulated primarily by hydrodynamic forces. To gain further insight into the regulation of this process, we investigated the response of blood flow velocity and cross-sectional area (CSA) of the internal jugular veins (IJVs) to local hemodynamic shifts. All procedures and assessments were performed on patients (n = 30) undergoing embolization of brain arteriovenous malformations (AVMs).

[Creatine in a metabolism of cell and its protective action at brain ischemia].

The aim of this review was the discussion of creatine involvement in metabolism of nervous tissue cells. The questions of creatine penetration through the blood brain barrier and creatine transporter expression were raised. Also mechanisms of creatine protective effect were considered at experimental models of brain ischemia.

[Appearance of stellate smooth muscle cells in the rat brain after transitory focal ischemia].

One of the poorly studied problems of the pathogenesis of the brain ischemic damage is the early reorganization of blood vessels in the zone of the transitory ischemia. The aim of the present study was to investigate the structural organization and cytochemical characteristics of smooth muscle cells (SMC) in the wall of the intracerebral blood vessels in 16 Wistar rats during the early postischemic period (48 hrs after a 30 minute-long ischemia). Examination of the lesioned hemisphere revealed the stellate cells, demonstrating positive reaction to alpha-smooth muscle actin, which seem to be a special population of structurally modified SMC, uncharacteristic to the intact brain of control animals (n=5).

Myocardial protection against global ischemia with Krebs-Henseleit buffer-based cardioplegic solution.

Background: The Krebs-Henseleit buffer is the best perfusion solution for isolated mammalian hearts. We hypothesized that a Krebs-Henseleit buffer-based cardioplegic solution might provide better myocardial protection than well-known crystalloid cardioplegic solutions because of its optimal electrolyte and glucose levels, presence of buffer systems, and mild hyperosmolarity.

Methods: Isolated Langendorff-perfused rat hearts were subjected to either global ischemia without cardioplegia (controls) or cardioplegic arrest for either 60 or 180 min, followed by 120 min of reperfusion.

[Effect of intragastric creatine glycine ethylic ether fumarate administration in a rat model of occlusive ischemia].

The aim of the study was to investigate neuroprotective effect of creatine glycine ethylic ether fumarate (creamide). The methods involved intragastric administration of creamide in doses of 30 and 50 mg/kg twice a day for 10 days. Focal 30 minutes cerebral ischemia model by endovascular suture occlusion of the middle cerebral artery in a rat with subsequent reperfusion period for 48 hours was produced.

Intestinal injury can be reduced by intra-arterial postischemic perfusion with hypertonic saline.

Aim: To investigate the effect of local intestinal perfusion with hypertonic saline (HTS) on intestinal ischemia-reperfusion injury (IRI) in both ex vivo and in vivo rat models.

Methods: All experiments were performed on male Wistar rats anesthetized with pentobarbital sodium given intraperitoneally at a dose of 60 mg/kg. Ex vivo vascularly perfused rat intestine was subjected to 60-min ischemia and either 30-min reperfusion with isotonic buffer (controls), or 5 min with HTS of 365 or 415 mOsm/L osmolarity (HTS(365mOsm) or HTS(415mOsm), respectively) followed by 25-min reperfusion with isotonic buffer.