Effect of Gonadotropin-Releasing Hormone Antagonist on the Expression Patterns of Insulin-Like Growth Factor 1, Androgen Receptor, and Luteinizing Hormone Receptor in an Experimental Rat Model of Functional Ovarian Cysts.

We studied the expression of insulin-like growth factor 1 (IGF-1), androgen receptor (AR) and luteinizing hormone receptor (LHR) in the ovaries under the conditions of the modeling and subsequent treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist (ant-GnRH). The intensity of IGF-1, LHR, and AR expression in the generative elements of rat ovaries changed under conditions of functional ovarian cysts simulation, as well as during treatment with ant-GnRH. In both experimental groups, the expression levels of the studied markers in preantral follicles and epithelial lining of cysts were found to be related to the number of growing follicles and cysts. A divergence of LHR and AR expression indices and a more pronounced decrease in the number of cystic cavities were observed in the group receiving ant-GnRH. These changes demonstrate a positive effect of ant-GnRH on intra-ovarian regulatory factors and a therapeutic effect in functional ovarian cysts.

Morphofunctional State of the Ovaries in Rats with Experimental Model of Functional Cysts and Their Treatment with Gonadotropin-Releasing Hormone Antagonist.

The morphofunctional features of the ovaries were evaluated in rats with functional ovarian cysts model treated with gonadotropin-releasing hormone antagonist. Administration of the antagonist significantly (p=0.009) reduced the number of cysts and the growth of follicles in the ovaries. The obtained results attest to a possibility of successful treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist.

[Structural changes in human brain tissue during prenatal alcoholization at different stages of intrauterine development]. / Strukturnye izmeneniya v tkani golovnogo mozga cheloveka pri prenatal'noi alkogolizatsii na raznykh srokakh vnutriutrobnogo razvitiya.

OBJECTIVE: To assess the degree of influence of intrauterine alcoholization on the formation of various structural components of the brain of human embryos. MATERIAL AND METHODS: Twenty-six samples of embryonic material from 8 to 11 weeks of intrauterine development were studied. The material was divided into four subgroups in accordance with the gestational age (Control 1 - 8-9 weeks of gestation and Control 2 - 10-11 weeks of gestation) and the history of the mother (presence or absence of the diagnosis «Alcoholism stage I-II¼ in the anamnesis). Morphometry was subjected to semi-thin sections stained by Nissl. The diameter and area of each individual tissue element (neuroblasts, glioblasts, vessels of the microvasculature, as well as the determination of the specific area (the ratio of the total area of the studied structure to the area of the entire section) and the calculation of the average number of these structures per unit area of the section, were determined. The AxioVision 4.8 program (Carl Zeiss, Germany) was used for analysis, and the Mann-Whitney test was used for statistical analysis of differences between the samples (significant differences, p<0.05). RESULTS: An insufficient increase in the area of vessels of the microvasculature was revealed in combination with a compensatory increase in their number per unit area of the section in the Alcohol groups compared with intact groups (48.5 µm2 vs 83.3 µm2, p<0.05). When comparing the sizes of glioblasts in the Control and Alcohol subgroups at different stages of development, a lag in the sizes of cellular structures in the Alcohol groups at the initial stages was revealed (average area 21.3 µm2 vs 32.1 µm2; 12.9 µm2 vs 13.3 µm2). When comparing data on later periods, no significant differences were found, only an increase in the specific number of cells in subgroup Alcohol 2 was noted (p<0.05). In neuroblasts, there was also a decrease in cell size with an increase in gestational age both among the Control and among the Alcohol subgroups. However, the cell sizes in Alcohol 2 exceeded those in Control 2 and their number was smaller (p<0.05). CONCLUSION: Alcohol leads to changes in the size and number of neuroblasts, glioblasts and vessels of the microvasculature and, as a result, to a disproportionate development of the entire brain tissue. The changes progress with an increase in the development period.

[Age-related structural changes in the cells of the primary visual cortex of rats under high-intensity light exposure.]

The experiment on 20 male Wistar rats has demonstrated that under light exposure 3 500 lux for 7 days on different-aged rats morphological changes are observed in the II, IV and V layers of the primary visual cortex. They manifest itself as percentage increase of reversibly and irreversibly altered neurons, mainly in the fourth layer in 18-month-old rats (p≤0,05). Thus, under light exposure in 18-month-old rats the percentage of hyperchromic wrinkled neurons runs up to to 6% (5; 8,5) and the percentage of neurons with total chromatolysis increases up to 10% (8,5; 14) in comparison with 1% (0,5; 14) and 6% (5; 8) in 3 month rats under light exposure, respectively (p≤0,05). The neural damage leads to the glial reaction, which is expressed by the percentage increase of glia with edema and swelling signs, hyperchromia without shrinkage of the nucleus and cytoplasm (p≤0,05), neuronophagy, and the intrusion of gliocytes into the neuron cytoplasm for initiation of intracellular repair. The destructive changes are characterized by hyperchromia of gliocytes with shrinkage of the nucleus and cytoplasm. The percentage of such gliocytes significantly increases in the IV layer in 18 month old rats under light exposure, in comparison with the indexes of young animals (p≤0,05).

[Potential of melatonin for prevention of age-related macular degeneration: experimental study].

Decline with age of the content of melatonin is considered as one of the leading mechanisms of aging and development of associated diseases, including age-related macular degeneration (AMD)--the disease, which becomes the most common cause of blindness and acuity of vision deterioration in elderly. The prospects of the use of melatonin in the prevention of AMD is being actively discussed, but as a rule on the basis of the results of the experiments on cells in retinal pigment epithelium (RPE). We showed previously that the senescence-accelerated OXYS rat is an adequate animal model of AMD, already used for identifying the relevant therapeutic targets. Here we have investigated the effect of Melatonin (Melaksen, 0,004 mg per kg--a dose equivalent to the recommended one for people) on the development of retinopathy similar to AMD in OXYS rats. Ophthalmoscopic examinations show that Melatonin supplementation decreased the incidence and severity of retinopathy and improved some (but not all) histological abnormalities associated with retinopathy. Thus, melatonin prevented the structural and functional changes in RPE cells, reduced the severity of microcirculatory disorders. Importantly, Melatonin prevented destruction of neurosensory cells, associative and gangliolar neurons in the retina. Taken together, our data suggest the therapeutic potential of Melatonin for treatment and prevention of AMD.

[Structural changes of eye chorioretinal complex after total cerebral ischemia and their correction].

Structural changes of eye chorioretinal complex were investigated in 40 adult male outbred albino rats after total transient cerebral ischemia using electron microscopy and morphometric analysis. Furthermore, the influence of a new sterically hindered phenolic antioxidant dibornol on these processes was estimated. Our studies demonstrated that total transient cerebral ischemia in rats resulted in the capillary thrombosis of the choriocapillary lamina of the uvea, structural disturbances of the blood-retinal barrier, degeneration of the retinal neurons and radial glia. Course administration of dibornol was shown to improve the microcirculation and to protect the retinal neuronal structures, pigment epithelium, and radial glia.

Morphological changes in retinal neurons in streptozotocin-induced diabetes mellitus and their correction with an isobornylphenol derivative.

Along with microangiopathy, one of the main causes of blindness in diabetic retinopathy consists of degeneration of retinal neurons. Electron microscopy and morphometric analysis were used to study structural changes in neurosensory cells, associative, and ganglion neurons in the retina in 30 while mongrel male rats with streptozotocin diabetes for two months and the effects of a new semisynthetic antioxidant 4-methyl-2,6-diisobornylphenol, a screened phenol, were evaluated. Destructive changes were found to affect the outer segments of neurosensory cells and ganglion neurons. The number density of neurosensory and ganglion cells decreased, and the proportion of these cells with pyknotic nuclei increased. 4-Methyl-2,6-diisobornylphenol had neuroprotective actions, preventing destructive changes to neurosensory cells and ganglion neurons.

Changes in the synaptoarchitectonics of the retina after light-induced damage and their correction with antioxidants of plant origin.

Changes in contacts between neurons in the internal reticular layer of the retina were studied in white rats 7 and 30 days after exposure to high-intensity light. Osmium preparations on day 7 demonstrated synapse destruction, predominantly of the "light" type of. Contrasting with phosphotungstic acid was used to study juxtamembrane formations of the system of subsynaptic units, i.e., dense projections and postsynaptic thickenings of synapses. The action of light was found to induce destructive changes in synapses, with decreases in the number density of synapses due to functionally active asymmetric contacts. On day 30 after light-induced damage, there was a significant increase in the number density of symmetrical contacts and a decrease in the content of asymmetric mature synapses. Courses of ascovertin and carovertin before and after exposure to light produced different degrees of restriction of synapse destruction and activated repair mechanisms mediated by hypertrophy and neosynaptogenesis. Carovertene had the greater effect.

[Morphological changes in retinal neurons in rats with streptozotocin diabetes and their correction by O-isobornylphenol derivative].

Along with microangiopathy, degeneration of retinal neurons is one of the basic causes of blindness in patients with diabetic retinopathy. Using the electronic microscopy and morphometric analysis, the structural changes of neurosensory cells, associative and ganglionic retinal neurons were studied in 30 albino outbred male rats with long term (2 months) streptozotocin diabetes and the effect of a new semisynthetic antioxidant belonging to a group of strictly hindered phenols (4-methyl-2,6-diisobornylphenol) on these parameters was evaluated. In diabetic rats, the destructive changes of external segments of neurosensory cells and ganglionic retinal neurons were found. The numerical density of neurosensory and ganglionic cells was reduced, while the proportion of these cells with pyknotic nuclei was increased. 4-Methyl-2,6-diisobornylphenol demonstrated neuroprotective effect by preventing destructive changes of neurosensory cells and ganglionic retinal neurons.

[Changes of synaptoarchitecture of the retina after the light-induced damage and their correction by plant antioxidants].

The changes of interneuronal contacts in the internal reticular layer of albino rat retina were studied 7 and 30 days after the exposure to high intensity light (6000 Lux for 6 h). In osmicated preparations, the "light" type of synapse destruction was predominant 7 days after the light-induced damage. Using the contrasting by phosphotungstic acid, paramembrane structures of the system of subsynaptic units--dense projections and postsynaptic condensations of synapses--were studied. It was found that the exposure to high intensity light resulted in the destructive changes of synapses and the decrease of their numeral density at the expense of the actively functioning symmetric contacts. 30 days after the light-induced damage, the numeral density of symmetric contacts was significantly increased, while the content of symmetric mature synapses was decreased. Course administration of ascovertine and carovertine before and after the exposure to light was found to have a differential effect on limiting the destruction of the synapses and on the activation of the repair mechanisms which are realized due to the hypertrophy and neosynaptogenesis. The highest effect was found after carovertine administration.

Clinical and morphological characteristics of chorioretinal degeneration in early aging OXYS rats.

OXYS rats are characterized by early development of cataract and chorioretinal degeneration with clinical manifestations similar to those observed in senile cataract and age-associated macular degeneration in humans. According to fundoscopy findings, the incidence of chorioretinal degeneration sharply increases in OXYS rats by the age of 4.5 months, when all animals develop signs of fundus oculi pathology. Morphological analysis of semithin sections of the posterior wall of the eye in OXYS rats aged 5 months showed that choroid vessels, pigmented epithelium, and radial glia were most vulnerable to injury. Retinal hypoxia and destruction of the pigmented epithelium associated with circulatory disorders in the choroid vessels presumably lead to injuries of the neurosensory cells (mainly the external segments) and a 3.5-fold increase in the percent of photoreceptors with nuclear pyknosis in comparison with the control. These results indicate that OXYS rats represent an adequate model of age-associated macular degeneration and can be used for studies of the pathogenesis of this condition and development of methods for its treatment and prevention.

Effects of carovertin on the reaction of retinal pigmented epithelium and radial glia to bright light.

Light exposure (6000 lux, 6 h) caused reactive changes in rat retinal pigmented epithelium and radial glia on day 1. Foci of lesions with virtually complete absence of the layers formed by neurosensory cells appeared on day 7. The number of destructively changed radial gliocytes in these foci was by one order of magnitude higher than in the control. Carovertin reduced destruction of pigmented epithelium and radial glia and reduced the area of lesion foci.

Structural changes in components of the blood-retina barrier in rat retina during photodamage in alloxan diabetes and their correction with ascovertin.

The outer part of the blood-retina barrier was most sensitive to light exposure (6000 lx, 6 h) during photodamage. It was manifested in hemodynamic disturbances, endothelial dysfunction, and focal death of the pigment epithelium. The photo effects increased during alloxan diabetes. The specific area of open vessels decreased, while the number of thrombotic vessels in the choroid increased. Administration of ascovertin improved hemodynamic parameters of the eye and decreased the specific area of focal damage.

Effect of ascovertin on morphological changes in rat retina exposed to high-intensity light.

Experiments on rats showed that high-intensity light exposure (6000 lux, 6 h) caused focal injuries in the retina. The most sensitive structures were neurosensory cells, pigmented epithelium, radial gliocytes, and choroid capillaries. Injection of ascovertin led to disappearance of foci of injuries, limited blood supply disorders in the retina, and destruction of neurosensory and glial cells.