Dynamics of granule cells migration into the internal granular layer in developing human cerebellum.

The aim of these investigations was to find out the dynamics of migration of granule cells into the internal granular layer in three different parts of cerebellar cortex. The dynamics of changes was followed in vermis, in lateral hemispheres and in flocculus. For that purpose, 25 fetal brains of different postovulatory age (12.5, 15, 17.5, 19.5, 21, 31 week and one brain of 6 days old newborn) were fixed in formalin, embedded in paraffin, than stained with Cresyl violet and cut in 6, 15 and 30 microm. Each fifth slice was analyzed using the light microscope and numerical density of granule cell nuclei was established by point counting method according to Weibel. Results show a steady increase of the granule cell population in the internal granular layer of all regions investigated, being still greater in vermis and in hemispheres. This increase in the cell number lasted during the whole period of intrauterine development. Moreover, according to the trend of the curves, the increase of the cell number continues even after the birth, suggesting that at least some synaptic connections of granule cells are not established yet. For each region the adequate mathematical model of migration dynamics was calculated.

Regression changes in inferior olivary nucleus compared to changes of Purkinje cells during development in humans.

Human fetal brains were investigated in order to establish the regressional process in two directly dependent structures: in the inferior olivary nucleus and in cerebellar Purkinje cells. Inferior olivary nucleus is the main origin of the climbing fibres, that form one of two direct input systems into the cerebellum. For the purpose 25 fetal human brains at various stages of development (12.5, 15, 16.5 19.5 24, and 31 postovulatory week), together with one brain of newborn (in further text: 41. postovulatory week) were used. Numerical density of nuclei in both regions was determined by stereological technique. In both structures appeared a reduction in the number of nuclei, showing specific dynamics during the intrauterine maturation. The data obtained were analyzed by graphical and numerical method, that allowed the formation of the adequate mathematical models for both structures, that precisely described their regression changes. The data presented indicate that the reduction is very pronounced until the 18-19 postovulatory week, and after that time it is remarkable slowed down. That period is therefore the probable breakpoint of the appearance of synaptic contacts between climbing fibres and Purkinje cell dendrites.

[Effects of ethanol on thyroid gland development]. / Efekat etanola na razvoj tireoidne zlezde.

Maternal ingestion of alcohol appears to cause a pattern of congenital anomalies with pre- and postnatal growth in the offspring. In order to study the possible implication of thyroid function in the effect of exposure to alcohol, we have studied structural alterations of this gland during early postnatal period (0-20 days) of the rats from alcohol-fed mother, which were given 15% ethanol as the only drinking solution daily one month before and during pregnancy and lactation. The results of the light-microscopic and stereological analysis clearly show that maternal ingestion of ethanol results in the stimulation off the thyroid gland of their pups. This was the most prominent in 20-day-old rats, what is substantiated by the much more irregular apical surface of the follicular cells, appearance numerous colloid droplets, significant increase both the volume density of follicular epithelium (p < 0.05) and interfollicular tissue (p < 0.001) and significant reduction in volume density of colloid (p < 0.001). These results suggest that maternal ethanol exposure disturbs the normal structure of the thyroid gland of their offspring what may, at least partly, mediate to alcohol-induced detrimental effect on growth and development in the fetus and neonate.

[Stereologic analysis of the human hypoglossal nucleus during the period ranging from the 22nd postovulatory week until birth]. / Stereoloska analiza jedara nucleus hypoglossusa kod coveka u periodu od 22. postovulatorne nedelje pa do rodenja.

The hypoglossal nucleus consists of the cells of the fourth stage of maturation according to Rakic. However, there are obvious differences and one of them is observable in the degree of staining intensivity of their Nissl bodies and nuclear inclusions. The stereological analysis revealed a constant decreasing of numerical density of the nerve cells nuclei in stages investigated. The decrease of the numerical density was highly significant (p < 0.001), probably due to the tissue growth and the total increase of nucleus i.e. its neuropi. The shrinkage of the tissue must be taken into consideration, too.

Regressional changes of human cerebellar cortex and hypoglossal nucleus during development.

In the development of nervous system, two processes are of a particular interest. It is well known that after a primary migration of cells, there appears a consecutive regression in cellular number, closely connected with the maturation of the nervous system. The dynamics of this reduction was investigated following the changes in number of cells in nucleus hypoglossus as well as that of Purkinje cells in two structures of cerebellar cortex--in vermis and in hemispheres. Cell nuclei were counted using the stereological technique, after a usual preparation. Data were collected from 20 human brains of different gestation age, i.e. at 12.5, 14, 17.5, 19.5, 24, 31, weeks of gestation and 6 day old newborn. After the graphical and numerical analysis of the data obtained, an adequate mathematical model was proposed. It is confirmed that a close agreement between biological data and decreasing two-exponential equation can be demonstrated, pointing out that the cellular reduction shows a proportional relation. The possible explanation could be that only the cells forming proper and useful connections and entering the informational system have a privilege to survive, and that all improper contacts lead to the rejection of cells or even of groups of cells.

[Morphologic characteristics of the vascular network of the dentate nucleus during development]. / Morfoloske karakteristike krvne mreze zupcastog jedra u toku razvoja.

The development of the blood network of the dentate nucleus was studied on 20 human fetal brains of different crown-rump length (CRL). In the stage of 17 to 20 weeks, the blood network of the dentate nucleus consisted of moderate spiral blood vessels. They anastomosed each other and made irregular elongated polyhedral meshes. From this meshwork, blood vessels of a greater volume arose and extended to the hilum of the nucleus. Between 23 and 25 weeks, a clear segmental vascular pattern was noticed. The capillary network was very dense. Along the outer surface of the nucleus the blood vessels which connected two secondary wrinkles of the gray matter were observed. In all the stages investigated the blood vessels were moderately spiral.

The development of the dentate nucleus in man.

The development of the dentate nucleus was studied on 12 brains of the human fetuses of different crown-rump length (CRL) and one newborn. The first appearance of the dentate nucleus was noticed in the fetus 12.5 weeks old. The dorsomedial lamina begins to grow in the 13th week and to fold in the 20th week. The ventrolateral lamina begins to grow in the 20th week and to fold in the 23.5th week. During the development of the dentate nucleus, 2 important periods can be determined. The first period corresponds to the first appearance of the dentate nucleus (12.5 weeks) and the second period corresponds to intensive growth of the dorsomedial and ventrolateral lamina (20-24.5 weeks).