There is a need to take the characteristics and possible influences of animals’ age and the anesthesia used in experiments on their outcomes into account to avoid producing distorted results at the preclinical research stage of new pharmaceutical substances and therapeutic strategies. This paper reports the effects of chloral hydrate on the morphological features of neurons, the reactions of neocortical microglia, and the functional status of elderly male Wistar rats (age 24 months). Differences were assessed in control rats and in the group given chloral hydrate at the dose required to achieve anesthesia (400 mg/kg body weight) 48 h after its administration. After administration of chloral hydrate, surviving animals (mortality rate 37.5

The cerebellum is a part of the brain that is very sensitive to the toxic effects of general anesthetics. The aim of this work was to evaluate the morphological response of neurons and microgliocytes in all layers of the cerebellar cortex to prolonged (6 h) exposure of sevoflurane (general anesthetic). It was shown that, after prolonged exposure of Wistar male rats to sevoflurane, structural and functional rearrangement were observed in all layers of the cerebellar cortex. In the molecular and ganglion layers the total density of neurons decreased. The number of morphologically altered cells of the molecular layer and Purkinje cells increased to 250 and 300%, respectively, due to both direct toxic effects of the anesthetic and disruption of interneuron connections. In the granular layer, the total density of the neuron population did not change and the number of morphologically altered neurons did not increase significantly. The number of microgliocytes revealed immunohistochemically increased significantly, and activation in response to neuronal death was weakly present. The absence of excessive activation of microgliocytes after prolonged exposure to sevoflurane is a positive result, since neuroinflammatory mediators are produced to a lesser extent and neurons do not experience additional damaging effects from microglia.

Hippocampus plays an important role in the cognitive mnestic functions. It coordinates emotional process, defines the intensity and specificity of behavioral, neuron and hormone reactions. Structural changes in hippocampus neurons can result in learning and memory disorders. The objective: to investigate morphometric parameters of hippocampus fields in rats after abdomen surgery with exposure to sevoflurane. Subjects and methods. The experimental research was performed using Wistar rats (n = 15). Rats from the experimental group (n = 7) had abdomen surgery with anesthesia with sevoflurane with the consequent continuous exposure to it (6 hours, 2 vol. % of sevoflurane, air flow – 1 l/min.). During 21 days rats from both groups had a number of behavioral tests. In 12 hours after the last behavioral test (on the 22-th day after the start of the experiment) the rats were decapitated with consequent brain extraction. The obtained materials were fixed in 10% neutral formalin on phosphate buffer (pH 7.4) for 24 hours minimum. Preparations of CA1, Ca2, Ca3, and Ca4 fields were studied under light microscope DM-750 (Leica, Germany) using the computer image analysis software of ImageScope M with 400-fold magnification. Results. The tests showed that cytoarchitectonics of hippocampus field was intact, pyramidal neurons had a large rounded nucleus with one, two or more distinct nucleoli. No pericellular and perivascular edema was detected. In the experimental group, all fields of the hippocampus had structural and functional changes. It manifested through both quantitative and qualitative signs of neuronal damage, especially in the Ca1 field. Segments of pyramidal neurons were disorganized, morphologically modified neurons were found: hyperchromatic shriveled neurons with no nucleus or poorly visible nucleus of the irregular shape. The appearance of morphologically changed neurons and disorganization of hippocampal layers led to changes in the width of pyramidal neurons segments. Conclusion. Morphological changes of hippocampal structures of rats after surgery and anesthesia may be the cause of cognitive functions decline during the postoperative period.

Expression of PECAM-1/CD31 protein (a biomarker for endothelial function and neovascularization processes) was studied in microvessels in layers II, III, and V of the cerebral cortex in Mongolian gerbils ( Meriones unguiculatus ) in the early (day 2) and late (day 7) parts of the reperfusion period after 7-min forebrain ischemia, ischemic postconditioning (iPostC), and sham-operated animals ( n = 60). In the latter, the lowest level of PECAM-1/CD31 immunoreactivity was seen in structures in layer III of the cerebral cortex. Reversible ischemic brain injury decreased the number of morphologically unaltered neurons in the neocortex with increases in the duration of the reperfusion period; cortical layers II, III, and V also showed increased levels of PECAM-1/CD31 immunoreactivity with significant increases in the late reperfusion period. iPostC consisting of three stimulatory episodes of reperfusion-ischemia (15/15 sec) led to significant increases in the number of morphologically unaltered neurons and PECAM-1/CD31 immunoreactivity in layers II and III in the early reperfusion period. In the later reperfusion period following iPostC, the number of unaltered neurons in layers II, III, and V of the cortex increased, while the level of PECAM-1/CD31 immunoreactivity decreased significantly. The results lead to the conclusion that the cytoprotective effect of iPostC in forebrain ischemia is mediated by a physiological adaptive mechanism leading to increases in PECAM-1/CD31 immunoreactivity in cortical microvessels in the early reperfusion period and a decrease in the later reperfusion period.

We analyzed pathomorphologic changes of lung interstitium tissue in male Wistar rats (average weight 250300 g, n=20) after single-pass intravenous administration 1ml (2 mg/ml) 13±2 nm silicon dioxide spherical shape nanoparticles. We estimated tissue reaction on 21 st and 60th days after injection. Diffuse infiltration of alveolar partitions increase was noticed (p <0,05); mast cells and eosinocytes pool increase was not significant. We did not revealed granulomas formation or pneumofibrosis. The revealed changes let us to suppose persistence of dispersible silica dioxide nanoparticles in lung interstitium on all terms of study. Cell reaction trends let us to propose that in lungs nanoparticles distribute with local interstitial macrophages.

The expression of Bcl-2 protein in pyramidal neurons in hippocampal fields CA1, CA2, CA3, and CA4 was studied in Mongolian gerbils ( Meriones unguiculatus ) in the early (two days) and late (seven days) reperfusion periods after 7-min ischemia of the forebrain, after use of ischemic postconditioning (IPostC) and in sham-operated animals ( n = 60). The highest level of Bcl-2 expression in the latter group was seen in neurons in field CA4 and the lowest in neurons in field CA1 ( p < 0.01). Reversible ischemic injury led to an increase in the deficit of morphologically unaltered neurons in the hippocampus at the later period of reperfusion and a significant decrease in neuronal Bcl-2 expression at the early reperfusion period, this decrease being significantly smaller in the late reperfusion period. IPostC consisting of three episodes of reperfusion-ischemia (15/15 sec) promoted a significant increase in the number of morphologically unaltered neurons in fields CA1 and CA3 in the early reperfusion period. An increase in the level of Bcl-2 expression was seen in the cytoplasm of morphologically unaltered neurons in all hippocampal fields. In the late reperfusion period after IPostC, the number of unaltered neurons was increased in fields CA1, CA3, and CA4 ( p < 0.05); only hippocampal field CA1 neurons showed a significant increase in Bcl-2 expression (by 12.7%, p < 0.01). These results lead to the conclusion that the cytoporotective effect of IPostC for hippocampal field CA1 is mediated by a mechanism leading to an increase in Bcl-2 expression, i.e., via blockade of apoptosis.

We studied 12-16 nm spherical silicone dioxide nanoparticles chronic toxicity on Wistar male rats (middle weight 250-300 g). We intravenously injected 1 ml silicone dioxide nanoparticles suspension and evaluated histological modifications in organs after 7, 21 and 60 days after injection. We detected mast cell migration into lungs, myocardium and liver tissues. Also we revealed macrophage granulomas around foreign bodies formation and liver tissue fibrous remodeling. This remodeling took place without precedence of destruction. We noticed that silicone dioxide nanoparticles injection was accompanied by evolution of chronic aseptic productive inflammation. The same type of inflammation take place in case of non-modified nanoparticles silicone dioxide intervention in sylicosis.

The aim of the present work was to investigate the effects of ischemic postconditioning (iPostC) on the viability of neurons in the various hippocampal fields and on cytoplasmic succinate dehydrogenase (SDH) activity in 30 Mongolian gerbils ( Meriones unguiculatus ). Ischemic brain damage was modeled by bilateral occlusion of both carotid artery for 7 min. iPostC was reproduced using three episodes of reperfusion (15 sec) and ischemia (15 sec). At 48 h after reperfusion, morphometric analysis was performed, along with histoenzymatic assessment of SDH activity in the cytoplasm of pyramidal neurons in hippocampal fields CA1, CA2, CA3, and CA4. The results of these studies showed that 7-min ischemia leads to significant decreases in the proportions of unchanged neurons in hippocampal fields CA1 (to 24%) and CA3 (to 56%); all hippocampal fields showed increases in cytoplasmic SDH activity, as compared with values in sham-operated animals. Use of iPostC led to significant increases in the proportion of unchanged neurons in hippocampal field CA1 (to 52.9%, p < 0.01) and field CA3 (to 88%, p < 0.05), which were accompanied by decreases in SDH activity in surviving neurons in all hippocampal fields.

We analyzed changes in activity of SDH, one of the most important enzymes of the Krebs cycle, in the cytoplasm of hippocampal and cortical neurons of Mongolian gerbils (Meriones unguiculatus) at the early and delayed reperfusion period after global brain ischemia. The data indicate that SDH activity in pyramidal neurons of various hippocampal areas and in neurons of II, III and V layers of cerebral cortex after 7-min forebrain ischemia depends on both the localization of these neurons and duration of the postischemic reperfusion. SDH activity in neurons significantly increased on days 2 and 7 after reperfusion.

The aim of the present work was to study the effects of ischemic postconditioning (IPC) on neuron viability in hippocampal field CA1 and cytoplasmic lactate dehydrogenase (LDH) activity in these cells in 30 male Mongolian gerbils (Meriones unguiculatus). Ischemic brain damage was modeled by bilateral occlusion of the common carotid arteries for 7 min. IPC was produced using three episodes of reperfusion-ischemia, 15 sec/15 sec. Morphometric analysis and histoenzymological LDH assay in the cytoplasm of hippocampal field CA1 neurons were performed 48 h after reperfusion, with quantitative cytometric assessment of enzyme activity. The results showed that 7-min ischemia led to a decrease in the number of viable neurons (to 24%) and decreased their LDH activity (from 0.260 ± 0.009 to 0.190 ± 0.006 units). Use of IPC led to a significant increase in the number of viable hippocampal field CA1 neurons (to 52.9%, p < 0.01), which was accompanied by an increase in their LDH activity (to 0.240 ± 0.008 units, p < 0.001).

The aim of the present work was to analyze changes in lactate dehydrogenase (LDH) activity in the cytoplasm of neurons in the hippocampus and cerebral cortex on Mongolian gerbils (Meriones unguiculatus) in the early and late reperfusion periods after global ischemia. LDH activity in pyramidal neurons in various hippocampal fields and in neurons in cerebral cortex layers II, III, and V after 7-min forebrain ischemia was found to depend on the locations of these neuron types and the duration of postischemic reperfusion. The dynamics of LDH activity in neurons were characterized by a significant decrease two days after reperfusion, with different levels of normalization by day 7 of the reperfusion period.

Both silicon and silica nanoparticles (SiNPs and SiO(2)NPs, 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 13 nm, 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 SiO(2)NPs (7 mg/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 SiO(2)NPs. In conclusion, both tested types of NPs are relatively biocompatible nanomaterials, at least when considering acute toxicity.

Effects of a peptide hormone—human recombinant erythropoietin (EPO)—on transmembrane potential (TMP) and a number of active mitochondria in rat thymocytes were studied in vitro using the fluorescent cationic probe 4-(p-dimethylaminostyryl)-1-methylpyridinium (DSM). It was established that EPO changes electric potentials on the surface of cellular membranes of rat thymocytes. Changes in fluorescent signals of DSM were found to depend on the EPO concentration and physiological status of thymus cells. EPO concentrations sufficient to increase average fluorescence intensity of DSM (\(\tilde F\)) in thymus cell mitochondria were established in vitro. These effects were stimulated by increasing the average number of energized mitochondria (Ñ m ) able to accumulate the fluorescent cationic probe. These changes can also be due to elevation of proton potential on the mitochondrial membrane and/or of electric potential of the plasma membrane. Experimental values of positive correlation coefficients between mean values of \(\tilde F\) and Ñ m in experimental (EPO) thymus cell samples differed from those in control. In the presence of EPO, \(\tilde F\) increased nonlinearly with Ñ m due to different responsiveness of thymocytes to EPO and change in polarization of the outer mitochondrial membrane in some EPO-stimulated cells. In the majority of cases, the peak in the distribution histogram of \(\tilde F\) was shifted towards augmentation of the DSM signal. The EPO response of cells isolated from different thymuses depended on the initial level of the average fluorescent signal of DSM in mitochondria, which testifies to differences in physiological statuses of animal thymuses and experimental animals at large.

Pathomorphology of the organ of Corti was studied on models of acute and chronic sensorineural damage to the acoustic analyzer. Peculiarities of hair cell degeneration, necrosis, and apoptosis in the organ were studied by light and scanning electron microscopy. The type of pathomorphological substrate in abnormalities of the organ of Corti depends on the intensity of the destructive exposure, but not on the nature of otopathological factors.

Morphological and quantitative histoenzymological changes in neurons of dog spinal cord and spinal ganglion were studied in acute and chronic experiments with epidural administration of 0.01% clofelin. No morphofunctional changes were revealed after bolus injection of clofelin in a single dose of 6.5 mg/kg. After administration of clofelin in a daily dose of 15 µg/kg for 14 days permeability of capillaries in the nervous tissue decreased at the site of injection, but increased in intact areas. Compensatory changes in energy supply to neurons manifested in activation of aerobic and anaerobic oxidation. Sufficient level of nucleic acids synthesis confirms qualitative validity of nervous cells. Epidural clofelin did not cause dystrophy and necrosis in neurons of the spinal and spinal ganglion.

Morphofunctional and histoenzymological changes in spinal cord neurons of mongrel dogs were studied after epidural administration of isobaric 2% lidocaine solution. Control animals received epidural 0.9% sodium chloride. The results obtained from these studies provide evidence for the absence of pathological structural-metabolic changes in nerve tissue after treatment with lidocaine. The occurrence of certain morphofunctional rearrangements in spinal cord neurons were typical of animals of both the experimental and control groups. The changes recorded varied within the limits of physiological variation and provided evidence predominantly of the functional response of these nerve tissue structures to epidural injections of both sodium chloride and lidocaine.