Decrease In Numerical Density Research Articles

Protective effect of taurine on cellular structures in rat hippocampus following ethanol intoxication.

Background. Distinct brain structures, in particular, the hippocampus, have a selective sensitivity to acute and chronic alcohol intoxication. Study of the pathogenesis of alcohol-related brain damage with a view to the development of methods of prevention and treatment is an urgent task.Objective.Our main interest was in elucidating the effects of the biologically active substance, such as taurine on cellular structures in the hippocampus following ethanol intoxication.Methods.We applied a histochemical method to estimate the Ca2 + -dependent acid phosphatase activity. The present study was carried out in female albino rats. All experimental animals received an ethanol (15%) diet as their sole source of fluid at various time points.To study the effect of taurine on cellular structures of the rat brain following short-term and chronic alcohol consumption, rats were given daily injections of taurine solution for 7 days. Results. The morphological picture of the hippocampus is characterized by swelling of granular cells in the dentate gyrus that undergo chromatolysis, as well as a decrease in numerical density and a weak expression of processes of pyramidal neurons in the early stages of alcohol consumption. Degenerative changes occur in pyramidal cells in the hippocampus in the middle periods of alcohol consumption. The density of neurons is decreased; pyramidal cells lose their characteristic shape. In the conditions of long-term alcohol consumption, not only changes in the size and number of pyramidal neurons but also in the volume of the hippocampus and its regions are observed. The morphological picture of hippocampal neurons is a morphological proof of the disorders of their metabolism. In rats treated with taurine, there are positive changes in the structural properties of neurons and an increase in phosphatase activity (increased metabolism) in the hippocampus, which determines cell survival and functional recovery of irritated neurons. Conclusion. The results indicate that taurine has a neuroprotective effect on cellular structures in rat hippocampus.

Status of the Microcirculatory Network as a Factor of Prognosis and Evaluation of Therapeutic Efficiency in Prostate Cancer Treated by High-Intensity Focused Ultrasound in Combination with Androgen Deprivation.

Immunohistochemical and morphometric analysis of the microcirculatory bed in the tumor and non-tumor parenchyma of the prostate was carried out with the use of endothelial cell marker CD34 in patients treated by high-intensity focused ultrasound (HIFU). The numerical density of microvessels in the adenocarcinoma focus did not correlate with the degree of its differentiation, while high values of this parameter were associated with lower incidence of local progression after HIFU. Effective HIFU ablation led to progressive fibrosis and significant reduction of the microcirculatory bed in zones of intact non-tumor glands in control samples; an inverse relationship between the degree of reduction of the microcirculatory bed and the probability of relapse was revealed. The use of HIFU in combination with androgen deprivation was associated with a decrease in numerical density of microvessels in zones of tumor and non-tumor parenchyma in patients with relapses.

Phenotypic differentiation of neurons in intraocular transplants

Neurochemical differentiation of neurons in transplants developing in rat anterior eye chamber was studied. Pieces of the somatosensory neocortex area, isolated from 17-day fetuses of Wistar rats, were used for the transplantation. The general cytological analysis and immunochemical identification of GABAergic neurons in neocortical transplants and in the appropriate brain area of the recipient rats (control) were carried out after 6 months. Cytoarchitectonics typical for neocortex was not revealed in the transplants. Furthermore, a 1.4-fold decrease in numerical density of the entire neuron population was found compared to the control. The proportion of GABAergic nerve cells in the transplanted tissue was reduced even more dramatically— by 13.1 times. The dimensions of all types of neurons, especially GABAergic cells, were greater in the transplants in oculo compared to neocortex in situ. The increase in size occurred mostly due to the cytoplasm. Thus, the nuclei of GABA-positive neurons in the transplants were larger by 1.2 times compared to the control and their perikarya were larger by 1.5 times. The obtained results showed that the conditions in the anterior eye chamber the most dramatically affect the differentiation of GABAergic neurons, and cell hypertrophy, probably, is the functional compensation of the decrease in their number. Considering the literature data on the increased excitability and synchronized neuronal activity in the intraocular transplants, it can be assumed that these transplants can be used as a model for studying the cellular mechanisms of nervous tissue epileptization under disinhibition conditions.

Chronic hypoxia-induced alterations in mitochondrial energy metabolism are not reversible in rat heart ventricles

Chronic hypoxia alters mitochondrial energy metabolism. In the heart, oxidative capacity of both ventricles is decreased after 3 weeks of chronic hypoxia. The aim of this study was to evaluate the reversal of these metabolic changes upon normoxia recovery. Rats were exposed to a hypobaric environment for 3 weeks and then subjected to a normoxic environment for 3 weeks (normoxia-recovery group) and compared with rats maintained in a normoxic environment (control group). Mitochondrial energy metabolism was differentially examined in both left and right ventricles. Oxidative capacity (oxygen consumption and ATP synthesis) was measured in saponin-skinned fibers. Activities of mitochondrial respiratory chain complexes and antioxidant enzymes were measured on ventricle homogenates. Morphometric analysis of mitochondria was performed on electron micrographs. In normoxia-recovery rats, oxidative capacities of right ventricles were decreased in the presence of glutamate or palmitoyl carnitine as substrates. In contrast, oxidation of palmitoyl carnitine was maintained in the left ventricle. Enzyme activities of complexes III and IV were significantly decreased in both ventricles. These functional alterations were associated with a decrease in numerical density and an increase in size of mitochondria. Finally, in the normoxia-recovery group, the antioxidant enzyme activities (catalase and glutathione peroxidase) increased. In conclusion, alterations of mitochondrial energy metabolism induced by chronic hypoxia are not totally reversible. Reactive oxygen species could be involved and should be investigated under such conditions, since they may represent a therapeutic target.

When cortical development goes wrong: schizophrenia as a neurodevelopmental disease of microcircuits

Schizophrenia probably has a developmental origin. This review refers to three of our published series of studies related to this hypothesis: loss of dendritic spines on cerebral neocortical pyramidal neurons, decreased numerical density of glutamatergic neurons, and microgliosis. First, brains of schizophrenic patients and non-schizophrenic controls were obtained post mortem and blocks of multiple cortical areas impregnated with a Rapid Golgi method. Spines were counted on the dendrites of pyramidal neurons of which the soma was in layer III (which takes part in corticocortical connectivity) and which met strict criteria for impregnation quality. Data were obtained blind: diagnoses were only revealed by a third party after measurements were completed. The mean spine count in all cortical areas studied in the control series was 243 mm(-1) of dendrite and in the schizophrenics 108. Measurements in frontal and temporal association cortex showed the greatest reduction in spine number in schizophrenia (299 in control frontal cortex and 101 in schizophrenics, and 276 mm(-1) in control temporal cortex and 125 in schizophrenics). There was no correlation of spine loss with age at death. Our results support the concept of a neurodevelopmental defect in the neuropil affecting glutamatergic neurons in schizophrenia and may help to explain loss of cortical volume without loss of neurons. In a second part of our study we used an antibody to the kainate receptor subunit GluR 5/6/7 and showed a decrease in numerical density of presumed glutamatergic neurons in schizophrenic orbitofrontal cortex. Finally, as glia play a major role in the developing nervous system, we investigated whether schizophrenia was associated with glial changes in frontal and temporal cortex. Astroglia and microglia were identified in schizophrenic and control brains, using antibodies to glial fibrillary acidic protein (GFAP) and class II human leucocyte antigen (HLA-DR), respectively. Significant increases were found in microglial numerical density in schizophrenics compared with controls: 28% in frontal area 9 (115 cells mm(-2) compared with 89), and a 57% increase in temporal area 22 (139 cells mm(-2) compared with 88). For both areas, astroglia showed no significant differences between schizophrenics and controls. No significant differences were found in cortical thickness or total neuronal numerical density between the two groups. This specific increase in numerical density of microglia in temporal and frontal cortex of chronic schizophrenics, not related to aging, could be related to possible changes in cortical neuropil architecture as revealed by loss of dendritic spines.

Effects of acute administration of ethanol on the rat adrenal cortex.

The purpose of this study was to investigate the effect of a single dose of ethanol on rat adrenal cortex and to determine whether the estrous cycle can influence this effect of ethanol. Adult female Wistar rats showing proestrus or diestrus Day 1 (n = 12) were treated intraperitoneally with ethanol (4 g/kg body weight). Untreated (n = 15) and saline-injected (n = 14) rats were used as controls. The animals were sacrificed by decapitation 0.5 hour after ethanol administration. Stereological analysis was performed on paraffin sections of adrenal glands stained with AZAN, and the following parameters were determined: absolute volume of the zona glomerulosa, the zona fasciculata and the zona reticularis, numerical density, volume and the mean diameter of adrenocortical cells and of their nuclei, and diameter and length of capillaries. The diameter and volume of adrenocortical cells in the zona fasciculata and the zona reticularis were significantly increased by acute ethanol treatment at proestrus. In the same group of animals, a single dose of ethanol induced significant decrease in numerical density of adrenocortical cells and of their nuclei in all three zones. Increased length of capillaries of the zona fasciculata as well as enhanced level of serum corticosterone was found in ethanol-treated rats at both phases of the estrous cycle, proestrus and diestrus Day 1. The obtained results indicate that a single dose of ethanol activates adrenal cortex in female rats and that the effect is more pronounced on morphometric parameters at proestrus.

Decreased levels of preprotachykinin-A and tachykinin NK 1 receptor mRNA in specific regions of the rat striatum after electroconvulsive stimuli

The effects of electroconvulsive stimuli on the expression of mRNAs coding for preprotachykinin-A and the substance P-sensitive tachykinin NK 1 receptor were examined in subregions of the rat striatum. In the electroconvulsive stimuli-treated animals, a 43% decrease in preprotachykinin-A mRNA was detected in the dorso-lateral caudate-putamen as compared to sham electroconvulsive stimuli treated animals. A 75% decrease in numerical density of tachykinin NK 1 receptor mRNA positive neurons was found in the caudal part of the nucleus accumbens core. These findings provide new evidence for selective effects of electroconvulsive stimuli on specific populations of neurons in the rat striatum.

Effects of clofibrate treatment and of starvation on peroxisomes, mitochondria, and lipid droplets in mouse hepatocytes: A morphometric study

Adult male mice of the NMRI strain were treated with a diet containing 0.5% clofibrate for 4 days to study its effects on peroxisomes, mitochondria, and lipid droplets in hepatocytes. Animals were also starved overnight to study the additional effects of starvation. Starvation of control animals had small effects on peroxisomes while the mitochondria became enlarged and occupied more of the cytoplasm. The number and fractional area of lipid droplets increased fivefold. Clofibrate treatment caused a doubling in number and average size of peroxisomes. No significant effects were observed in the number of mitochondrial profiles or lipid droplets although the size of the latter decreased to a third the value of the fed control. Starvation of clofibrate-treated animals led to a slight increase in the number of peroxisomes although their average size decreased by 30%. Mitochondrial average area increased and their fractional cytoplasmic area increased despite the decrease in numerical density. The number of lipid droplets increased twofold compared to that of clofibrate-treated animals while the size was not affected.

Morphometric analysis of the vagus nerve in non-diabetic and ketonuric diabetic Chinese hamsters

Morphometric analysis of axons from the ventral division of the vagus nerve of ketonuric diabetic Chinese hamsters and age-sex matched non-diabetic controls was performed to determine the frequency distribution and numerical and volume density. Myelinated fibres of diabetics displayed a significant reduction in diameter ( P<0·001) compared with controls, which was correlated inversely with progressive ketonuria ( P<0·05). The reduced calibre of myelinated fibres was the result of thin myelin sheaths rather than a reduction in axon diameter. A marked decrease in numerical density ( P<0·05) and volume density ( P<0·005) was found in the myelinated fibres of diabetics compared with controls. Non-myelinated axons showed a significant shift to smaller diameter ( P<0·001) in diabetics, which was correlated inversely with duration of ketonuria ( P<0·05). Numerical density of non-myelinated axons was increased ( P<0·01) in diabetic hamsters whereas volume density was comparable in diabetic and control animals. These data provide morphological evidence of impairment in the parasympathetic nervous system which may be a major factor underlying previously reported gastrointestinal and pancreatic islet dysfunction in the diabetic Chinese hamster.

Chlordecone-induced potentiation of carbon tetrachloride hepatotoxicity: A morphometric and biochemical study

The present study, conducted over a time course of 36 hr after CCl 4 administration, describes sequential morphometric and biochemical changes which occur in livers of rats exposed to a combination of low levels of chlordecone (10 ppm for 15 days) and a single ip injection of CCl 4 (0.1 ml/kg). Those changes were compared to hepatic alterations which occur in rats that received the same dose of chlordecone or CCl 4 alone. Biochemical studies showed only trivial increases in levels of glutamic-pyruvic transaminase (GPT), glutamic-oxalacetic transaminase (GOT), and moderate but temporary increases in isocitrate dehydrogenase (ICD) after CCl 4 alone. The combination of chlordecone and CCl 4 resulted in significantly greater elevations of all three serum enzymes at all time intervals examined. Morphometric data showed no difference between normal diet controls and animals exposed to chlordecone alone as far as numerical density of hepatocytes or volume densities of hepatocytes with glycogen, lipid, dilated rough endoplasmic reticulum (RER), pyknosis, or mitoses. Morphometric analysis of livers from animals that received CCl 4 alone showed decreases in numerical density, temporary decrease in precentage of hepatocytes containing glycogen, an increase in hepatocytes containing lipid, temporary increase in hepatocytes with dilated RER, and temporary increases in pyknotic nuclei. Soon after the initial hepatic injury was histologically evident between 4 and 6 hr, the number of mitoses increased dramatically and this progressed until complete recovery from CCl 4 damage. From all indices of damage, complete recovery was evident by 36 hr after CCl 4 administration. Morphometric analysis of livers from rats that received the chlordecone + CCl 4 combination showed decrease in numerical density, consistent and progressive decrease in percent of hepatocytes containing glycogen, progressive increase in hepatocytes containing lipid, progressive increase in cells with dilated RER, and a progressive increase in cells with pyknotic nuclei. Number of mitoses remained suppressed, in notable contrast to the animals receiving CCl 4 alone. These studies suggest that two aspects of chlordecone potentiation of CCl 4 hepatotoxicity might be of mechanistic interest: first, the initial, progressive, and remarkably greater CCl 4 injury in chlordecone-treated animals, and second, the mechanism for the suppression or prevention of hepatocellular repair and renovation, which leads to complete recovery of animals receiving CCl 4 alone while leading to total hepatic failure and death of animals receiving the combination treatment.