Biomedical subjects
Publications and source records attributed to N Zecević.
Patient K.N., age 30, nulliparous deliveries and with one miscarriage, was admitted to the Institute of Gynecology and Obstetrics, Clinical Center of Serbia, in December 2000 with the following diagnosis: Uterine myoma and adnexal mass.
Myelin basic protein (MBP) is a major myelin constituent produced by oligodendrocytes in the central nervous system (CNS). Expression of MBP was considered to be a marker for oligodendrocyte differentiation and myelination in the developing CNS. In this study, expression of myelin basic protein (MBP) and its messenger RNA (mRNA) was examined in human embryos and fetuses ranging in age from 5 to 20 gestational weeks (g.w.). We were able to demonstrate that MBP antibody labels cells in both human nervous and non-nervous tissues beginning from early embryonic life (5-6 g.w.). MBP positive (MBP+) cells were rounded, with either no cell processes or only 1-2 short processes, and were located in caudal regions of the CNS. MBP+ cells were also observed in the non-nervous tissue, such as leptomeninges, choroid plexus, and connective tissues. A number of MBP+ cells in nervous and non-nervous tissues were morphologically similar to macrophages and showed a positive reaction to macrophage-microglia markers: lectin (RCA-1) and the monoclonal antibody (EBM-11) to human macrophage antigen CD68, whereas they were negative for neuronal, astroglial, or marker for oligodendrocyte progenitors. At the same embryonic age, 5 g.w. and onward, the MBP mRNA was observed in the CNS by in situ hybridization. The results of this study show that MBP immune reaction is spread in a large area of the CNS prior to myelin appearance. In addition, for the first time it has been demonstrated that the same population of cells could be labelled with both MBP and macrophage markers. These results indicate that MBP, or MBP-related proteins, could represent a link between the immune and nervous system during early development. Thus, besides the well established role in myelination, these proteins might have an additional and still unknown function in development.
Cellular composition and lamination of the telencephalic wall (TW) was studied with Golgi impregnation in human embryos before and during the cortical plate formation (5, 6-7 and 7-8 gestational weeks (g.w.)). During this period, the telencephalic wall increased in width and lamination pattern became complex while cellular morphology reflected progressive differentiation. At 5 g.w. (Carnegie stage 16) TW was 140 microns wide and had two zones, marginal (MZ) and ventricular (VZ). It was built exclusively of bipolar ventricular cells and their upward directed processes. One week later, at 6 g.w. (stages 17 and 18) the telencephalic wall displayed three zones (VZ, intermediate-IZ, MZ) and increased to 220 microns. Sparse detached cells were found in the VZ while more of these cells were observed above VZ, in the incipient intermediate zone. These neurons were either simple or branched bipolar, and mainly oriented vertically in respect to the outer surface. However, horizontally oriented cells were also noticed either at the VZ/IZ border or immediately below the pia, where they probably represented Cajal-Retzius neurons. At 7-8 g.w. (stages 20-22), the cortical plate appeared between the IZ and the MZ at the ventrolateral level of the telencephalic wall. Intermediate zone could be further divided into a more superficial part or a presubplate layer (IZ1) and a deep part or a future white matter (IZ2). Thus, at this stage, TW consisted of five zones (VZ, subventricular, IZ with the presubplate, cortical plate-CP and MZ). The width of TW increased to 370-400 microns. Cortical plate cells were fusiform, with the apical dendrite branching into the MZ, and the axon directed in the opposite direction. Below it, differentiated neurons of the presubplate displayed a variety of morphological forms. The presence of horizontally oriented cells on the border of ventricular and subventricular zone was noteworthy. Impregnated bundles of horizontal fibres were encountered in the IZ and MZ of the telencephalic wall at 6 g.w. Their number increased in 7- to 8-g.w. embryos, especially in the lower (future white matter) and upper (future subplate) intermediate zone. Our results on the cellular development of the cortical anlage, as revealed by Golgi method, not only support results obtained on different experimental animals but also add new relevant evidence about human development. Data on transition of simple bipolar ventricular cells to different neuronal shapes as constituents of emerging new laminae were not available for human cortical anlage.
Qualitative and quantitative parameters of the early neuronal development of the thalamus were examined in human embryos and fetuses ranging in age from 5-16 gestational weeks (g.w.) using Nissl stained and Golgi impregnated tissue. In the earliest period analyzed, from 5-6 weeks of gestation, dorsal and ventral parts of the human thalamus were poorly differentiated structures forming the sides of the third ventricle. At 6 g.w., the prospective thalamic anlage consisted of the ventricular (VZ), the intermediate (IZ) and the marginal zones (MZ). The neurons in the VZ were bipolar and radially arranged to the ventricular surface. From 6-8 gestational weeks detached bipolar or branched bipolar cells with horizontal or oblique orientation were encountered in the IZ and occasionally in the MZ. In the period between 10-14 weeks of gestation, segregation of neurons into different thalamic nuclei began. The lateral geniculate nucleus, centrum medianum and mediodorsal nucleus were the first to be distinguished. In comparison with the previous period, the neurons throughout the rostro-caudal axis of the thalamus were more differentiated, with a higher number of primary dendrites that were often bifurcated. This resulted in various shapes of immature neurons: simple uni- and bipolar (type 1), branched uni- and bipolar (type 2) and young multipolar (type 3). In addition, the first spines were frequently observed on dendrites at 12 weeks of gestation. At 14-16 weeks of gestation, segregation of the neurons into thalamic nuclei continued. The neurons exhibited further dendritic differentiation that followed the caudo rostral gradient. For the first time, multipolar neurons, especially in the caudal part, could be subdivided into two classes: multipolar with a 'bushy' appearance, the result of many primary dendrites with several bifurcations and 'simpler' multipolar neurons with fewer and less branched primary dendrites. Neuronal differentiation was further expressed by an increase in the total dendritic length and somatic surface, up to six and three times, respectively, from the earliest period analyzed to 16 weeks of gestation. Dendritic length increased initially by the formation of new primary branches and their elongation and secondly by formation of higher branch orders. At 16 g.w., a group of immature cells were observed dorsally, on the frontal sections through the rostral thalamus. Its ganglionic eminence origin is discussed.
We correlated neuroanatomical developmental parameters with sequential ultrasonography scans to reveal the structural basis of functional recovery after early focal hypoxic lesions of the human frontal lobe in premature infants. We studied the transient fetal subplate zone in the premotor and prefrontal cortex in premature, newborn, infant, and young adult brains by acetylcholinesterase (AChE) histochemical, Golgi, and immunocytochemical methods. The structural in vivo rearrangements of the cerebral wall after perinatal lesions were studied on serial real-time sector scans (5-MHz transducer). The subplate zone contains "waiting" axons and randomly oriented fetal neurons, its developmental peak is between 22 and 34 weeks of gestation, and it is present in the frontal cortex of newborns and disappears after the sixth postnatal month, but individual subplate-like neurons remain until adulthood. Ultrasonography revealed remarkable structural rearrangements of the cerebral wall when the hypoxic lesion occurred during the developmental peak of the subplate zone: anechoic cavities ("cysts") develop rapidly (within 3 weeks) in premature brains, the rebuilding of these lesions continues after birth, and cavities disappear around the 11th month. We propose that the transient population of "waiting" axons and cells of the subplate zone participate in the structural and functional plasticity of the human cerebral cortex after perinatal brain damage.
The importance of afferent fibers in the final shaping of the central nervous system has been well established in several papers. In order to study how much one can influence cortical development by changing afferent input to the cortex cerebri, we transected corpus callosum in rats at 2 or 3 postnatal days. Equal numbers of lesioned and control animals were transcardially perfused with mixed aldehydes at postnatal day 6 (P-6) or P-14. Brain tissue was processed for Golgi impregnation, Nissl stain, and quantitative electron microscopic analysis. Morphometric image analysis (MOP 3) of the primary sensory area did not show significant differences with respect to cortical depth and total and apical dendritic length. The cross-sectional area and maximal diameter of neuronal cell bodies were smaller in P-14-lesioned animals. Ultrastructural analysis of the cortex revealed that synaptic density was not reduced in lesioned animals. In conclusion, early in development, rat brain can compensate for major changes in the commissural afferent system.
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