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Saint Petersburg, Russia

Ivanov S.,Institute of Experimental Medicine | Zhuravsky S.,Institute of Experimental Medicine | Yukina G.,Ip Pavlov Federal Medical University | Tomson V.,Ip Pavlov Federal Medical University | And 2 more authors.
Materials | Year: 2012

Both silicon and silica nanoparticles (SiNPs and SiO2NPs, respectively) are currently considered to be promising carriers for targeted drug delivery. However, the available data on their in vivo toxicity are limited. The present study was aimed at investigation of SiNP and SiO2NP (mean diameter 10 and 13nm, respectively) toxicity using both morphological and functional criteria. Hematological and biochemical parameters were assessed in Sprague-Dawley rats 5, 21 and 60 days after administration of NPs. Inner ear function was determined using otoacoustic emission testing at 21 and 60 days after infusion of NPs. Furthermore, the histological structure of liver, spleen and kidney samples was analyzed. Intravenous infusion of SiNPs or SiO2NPs (7mg/kg) was not associated with significant changes in hemodynamic parameters. Hearing function remained unchanged over the entire observation period. Both inter- and intragroup changes in blood counts and biochemical markers were non-significant. Histological findings included the appearance of foreign body-type granulomas in the liver and spleen as well as microgranulation in the liver after administration of NPs. The number of granulomas was significantly lower after administration of SiNPs compared with SiO2NPs. In conclusion, both tested types of NPs are relatively biocompatible nanomaterials, at least when considering acute toxicity. © 2012 by the authors.

Shmonin A.,Ip Pavlov Federal Medical University | Melnikova E.,Ip Pavlov Federal Medical University | Galagudza M.,Ip Pavlov Federal Medical University | Vlasov T.,Ip Pavlov Federal Medical University
International Journal of Stroke | Year: 2014

Background: The refinement of experimental stroke models is important for further development of neuroprotective interventions. Aims and/or hypothesis: Our goal was to study the reproducibility of outcomes obtained in five rat models of middle cerebral artery (MCA) ligation in order to identify the optimal model for the preclinical studies. Methods: In Part 1 of the experiments, systolic blood flow velocity (sBFV) and cerebral area at risk (AR) were determined immediately after the onset of brain ischemia induced in different ways in Wistar rats. After that, another set of experiments was performed (Part 2 of the experiments), now aimed at the assessment of the delayed outcome of five different models of cerebral ischemia designated as Versions 1-5. The versions were: Version 1 - 40-minute left MCA (LMCA) occlusion with reperfusion; Version 2 - permanent LMCA ligation; Version 3 - permanent ligation of both LMCA and left common carotid artery (CCA); Version 4 - permanent LMCA and bilateral CCA (bCCA) ligation; Version 5 - permanent LMCA ligation and 40-minute bCCA occlusion. The infarct size (IS) was quantified using triphenyltetrazolium chloride staining. The severity of neurological deficit was assessed by the Garcia score. The extent of brain edema was determined by calculating the difference in volumes of affected and contralateral hemispheres. Results: Within a relatively big AR, Versions 1 and 2 resulted in a small IS [0·2 (0·0; 0·4)% and 0·3 (0·0; 0·7)%, respectively, P>0·05]. Unlike that and comparable with AR, Version 3 resulted in a greater, albeit more variable IS [5·9 (2·1; 8·3)%, P<0·0001 vs. Version 2]. Also comparable with AR, Versions 4 and 5 produced greatest values of IS [14·5 (11·4; 17·9)% and 11·3 (10·1; 14·2)%, respectively]; this parameter was most reproducible in Version 5. A significant decrease in neurological deficit score was found in Versions 4 and 5. Again, the reproducibility of the data on neurological outcome was higher in Version 5 versus Version 4. Conclusions: Comparative analysis of several Versions of focal cerebral ischemia within a single study might be helpful in better understanding of the mechanisms underlying the development and aftermath of stroke. Permanent LMCA ligation plus transient bilateral CCA occlusion produced most consistent results and might be recommended for preclinical studies. International Journal of Stroke. © 2012 World Stroke Organization.

Karpov A.A.,Ip Pavlov Federal Medical University | Uspenskaya Y.K.,Ip Pavlov Federal Medical University | Minasian S.M.,Ip Pavlov Federal Medical University | Puzanov M.V.,Heart Genetics | And 4 more authors.
International Journal of Experimental Pathology | Year: 2013

This study aimed to investigate the effect of bone marrow- and adipose tissue-derived mesenchymal stem cell (BM-MSC and AD-MSC respectively) transplantation on left ventricular function and infarct area (IA) in the rat model of ischaemic heart failure. In anaesthetized Wistar rats, the left coronary artery (LCA) was occluded for 40 min with subsequent reperfusion for 7 days. Seven days following surgery, the animals with LCA occlusion/reperfusion were randomized into three groups: (i) Controls received intramyocardial injection of vehicle at three different locations within the peri-infarct zone, (ii) BM-MSC: cells were injected in the same way as in previous group (106), (iii) AD-MSC: using the same protocol as used in the BM-MSC group. In addition there was also a sham-treated group that had no injection. Two weeks following MSC transplantation, the hearts were isolated and perfused according to the Langendorff method followed by 30-min global ischaemia and 90-min reperfusion. After this IA was determined histologically. During Langendorff perfusion initial and postischaemic LV functions were the same in all groups although LV pressure at the 10th minute of reperfusion was higher in the AD-MSC group compared to controls. However, LV pressure during 30-min global ischaemia was significantly higher in BM-MSC as compared to controls and AD-MSC. The sham treated animals showed the same results as those seen with BM-MSC. Thus, BM-MSC transplantation, in contrast to transplantation of AD-MSC, resulted in better preservation of the LV ability to contract during ischaemia. Furthermore, IA was significantly smaller in BM-MSC group as compared to the controls and the AD-MSC groups. Thus this study has demonstrated that treatment with BM-MSC both ameliorates LV function and reduces histological scar size. © 2013 International Journal of Experimental Pathology.

Shcherbak N.,Ip Pavlov Federal Medical University | Popovetsky M.,Ip Pavlov Federal Medical University | Galagudza M.,Ip Pavlov Federal Medical University | Barantsevitch E.,Ip Pavlov Federal Medical University | Shlyakhto E.,Ip Pavlov Federal Medical University
International Journal of Experimental Pathology | Year: 2013

Cerebral ischaemic postconditioning (PostCon) is a recently discovered endogenous neuroprotective phenomenon that occurs after several brief bouts of reperfusion/ischaemia instituted immediately after prolonged cerebral ischaemia. Data on the extent of PostCon-mediated infarct size limitation in models of focal cerebral ischaemia-reperfusion are controversial. In this study, we investigated the infarct-limiting effect of PostCon in the rat model of focal cerebral ischaemia-reperfusion. The relationship between anatomic pattern of the middle cerebral artery (MCA) and infarct size was also studied. The protocol of PostCon consisting of five episodes each of 10-s ischaemia and 10-s reperfusion was protective in terms of infarct size limitation only in animals with the typical bifurcating MCA branching pattern. The anatomic pattern of the MCA should be considered as one of the important factors influencing the outcome of neuroprotection studies. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

Kornyushin O.,Ip Pavlov Federal Medical University | Galagudza M.,Ip Pavlov Federal Medical University | Kotslova A.,Ip Pavlov Federal Medical University | Nutfullina G.,Ip Pavlov Federal Medical University | And 4 more authors.
World Journal of Gastroenterology | Year: 2013

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 (HTS365mOsm or HTS415mOsm, respectively) followed by 25-min reperfusion with isotonic buffer. The vascular intestinal perfusate flow (IPF) rate was determined by collection of the effluent from the portal vein in a calibrated tube. Spontaneous intestinal contraction rate was monitored throughout. Irreversible intestinal injury or area of necrosis (AN) was evaluated histochemically using 2.3.5-triphenyltetrazolium chloride staining. In vivo, 30-min ischemia was followed by either 30-min blood perfusion or 5-min reperfusion with HTS365mOsm through the superior mesenteric artery (SMA) followed by 25-min blood perfusion. Arterial blood pressure (BP) was measured in the common carotid artery using a miniature pressure transducer. Histological injury was evaluated in both preparations using the Chui score. RESULTS: Ex vivo, intestinal IRI resulted in a reduction in the IPF rate during reperfusion (P < 0.05 vs sham). The postischemic recovery of the IPF rate did not differ between the controls and the HTS365mOsm group. In the HTS415mOsm group, postischemic IPF rates were lower than in the controls and the HTS365mOsm group (P < 0.05). The intestinal contraction rate was similar at baseline in all groups. An increase in this parameter was observed during the first 10 min of reperfusion in the control group as compared to the sham-treated group, but no such increase was seen in the HTS365mOsm group. In controls, AN averaged 14.8% ± 5.07% of the total tissue volume. Administration of HTS365mOsm for 5 min after 60-min ischemia resulted in decrease in AN (5.1% ± 1.20% vs controls, P < 0.01). However, perfusion of the intestine with the HTS of greater osmolarity (HTS415mOsm) failed to protect the intestine from irreversible injury. The Chiu score was lower in the HTS365mOsm group in comparison with controls (2.4 ± 0.54 vs 3.2 ± 0.44, P = 0.042), while intestinal perfusion with HTS415mOsm failed to improve the Chiu score. Intestinal reperfusion with HTS365mOsm in the in vivo series secured rapid recovery of BP after its transient fall, whereas in the controls no recovery was seen. The Chiu score was lower in the HTS365mOsm group vs controls (3.1 ± 0.26 and 3.8 ± 0.22, P = 0.0079 respectively,), although the magnitude of the effect was lower than in the ex vivo series. CONCLUSION: Brief intestinal postischemic perfusion with HTS365mOsm through the SMA followed by blood flow restoration is a protective procedure that could be used for the prevention of intestinal IRI. © 2013 Baishideng. All rights reserved.

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