Papers by Natasa Jovanov Milosevic
Journal of Anatomy, May 9, 2019
The early development and growth of the corpus callosum are supported by several midline transien... more The early development and growth of the corpus callosum are supported by several midline transient structures in mammals that include callosal septa (CS), which are present only in the second half of gestation in humans. Here we provide new data that support the guidance role of CS in corpus callosum development, derived from the analysis of 46 postmortem fetal brains, ranging in age from 16 to 40 post conception weeks (PCW). Using immunohistochemical methods, we show the expression pattern of guidance cues ephrinA4 and neogenin, extracellular protein fibronectin, as well as non-activated microglia in the CS. We found that the dynamic changes in expression of guidance cues, cellular and extracellular matrix constituents in the CS correlate well with the growth course of the corpus callosum at midsagittal level. The CS reach and maintain their developmental maximum between 20 and 26 PCW and can be visualized as hypointense structures in the ventral callosal portion with ex vivo (in vitro) T2-weighted 3T magnetic resonance imaging (MRI). The maximum of septal development overlaps with an increase in the callosal midsagittal area, whereas the slow, gradual resolution of CS coincides with a plateau of midsagittal callosal growth. The recognition of CS existence in human fetal brain and the ability to visualize them by ex vivo MRI attributes a potential diagnostic value to these transient structures, as advancement in imaging technologies will likely also enable in vivo MRI visualization of the CS in the near future.
The mammalian neostriatum is organised as a heterogenous mosaic of structurally and functionally ... more The mammalian neostriatum is organised as a heterogenous mosaic of structurally and functionally different compartments ; striosomes and matrix, distinguishable by their time of neurogenesis and neurodiferentiation, afferenet and efferent connections and distribution of neuroactive polypeptides. This mosaical organization is most apparent during fetal and early postnatal development, and differs from the one described in the adult brain. The exact relationship between the fetal and adult mosaic organization, as well as the molecular mechanisms that rely under it, are still unknown. Studies show that corticostriatal afferents connect with the neostriatum selectively with the striosome or matrix region and that striosome and matrix cells can segregate in the absence of dopamine afferents. Also, during neostriatum formation, newly arrived striatal neurons which will form the striosomes tend to selectively aggregate. This suggests that the cell surface and extracellular matrix (ECM) molecules play a crucial role in the formation of neostriatal compartments. In a present study, we evaluated at the histological level the expression pattern of the ECM neurocan (NCAN), a chondroitine-sulphate proteoglycan that can modulate neuronal migration and adhesion, in the human fetal neostriatum. We used indirect immunohystochemical staining on postmortal brain tissue from 12 to 40 gestation weeks (GW). NCAN immunoreactivity is first recognized in the fetal neustriatum at 16 GW in cell islands that match the cytoarchitectinical cell islands recognized on Nissl sections. The peak of NCAN immunoreactivity is observed between the 19th – 23rd GW in a tight cell-free zone that surrounds the striosomes – the peristriosomes or perimeters, which are most pronounced during fetal and early postnatal development. At GW 21 NCAN shows a shift in immunoreactivity – it is visible in the matrix. After the 23rd GW neurocan expression declines untill GW 27 when its expression ceases. We propose that the selective expression of neurocan in the different modules of the fetal striatum reflects the differences in the sequence of growth and maturation of striatal afferents, and/or that neurocan has a role in forming the boundaries between striatal modules.
Numerous studies on poultry as an important animal models in the investigation of non-infectious ... more Numerous studies on poultry as an important animal models in the investigation of non-infectious diseases in humans have been successfully carried out and published in numerous scientific journals around the world. This report should not be taken as definitive, rather as a short review of some successfully completed investigations on poultry as animal models in Croatia (cardiovascular diseases in chickens. It is also questioning the justification of the current obstacles to the continuation and completion of research of e.g. degenerative retinopathy in chickens (very similar to retinitis pigmentosa in humans), acute heart diseases (in broiler turkey as a model), and also the neglection of other species of birds as animal models (Parrot Proventricular Dilatation Disease as the model in the study of Guillain-Barre syndrome in humans).
Veterinary Archives
The primary objective of this study was to determine which closure technique -simple interrupted ... more The primary objective of this study was to determine which closure technique -simple interrupted suture (SIS), simple continuous suture (SCS), interrupted double loop closure (IDLC) or continuous double loop closure (CDLC) -results in stronger wound repair after midline laparotomy. Surgery was performed on 48 male rats. On the 5 th postoperative day the rats were sacrificed and wound strength was measured by inserting a balloon into the abdomen and filling it with air until the abdomen burst. Pressure was measured in millimetres of mercury. Abdominal bursting pressure was 281.25 ± 26.5 mm Hg (mean ± SD) in the SIS group, 287.91 ± 29.6 mm Hg in the SCS group, 295.41 ± 31.9 mm Hg in the IDLC group and 314.58 ± 24.7 mm Hg in the CDLC group (P<0.05). Closure of the midline abdominal incisions using SCS has almost the same wound strength as SIS or IDLC but it is recommended because of simplicity, speed, and costs. CDLC ensures the greatest wound strength on the basis of the intraperitoneal pressure required to burst the abdomen. The results of the comparison of the SIS to SCS, as well as IDLC to CDLC, show that continuous suture techniques are more favourable than the interrupted suture techniques from which they were derived.
Collegium antropologicum, 2008
Investigation of the developmental potential of immature tissues is important for novel approache... more Investigation of the developmental potential of immature tissues is important for novel approaches to human regenerative medicine. Development of the fetal neural retina has therefore been investigated in two experimental systems. Retinas were microsurgically isolated from 20-days-old rat fetuses and cultivated in vitro for 12 days or transplanted in vivo under the kidney capsule of adult males for as long as 6 months. Shedding of the photoreceptor outer segment which is a process occurring at the terminal stage of photoreceptor differentiation was observed in culture by transmission electron microscopy (TEM). In transplants, no photoreceptors were found although markers of terminal neural and glial differentiation (e,g. synaptophysin, chromogranin and glial fibrilary acidic protein--GFAP) along with the molecules involved in the process of differentiation (guidance molecule semaphorin IIIA and chondroitin sulfate proteoglycan) were expressed. Semaphorin was differentially expressed...
The primary objective of this study was to determine which closure technique - simple interrupted... more The primary objective of this study was to determine which closure technique - simple interrupted suture (SIS), simple continuous suture (SCS), interrupted double loop closure (IDLC) or continuous double loop closure (CDLC) - results in stronger wound repair after midline laparotomy. Surgery was performed on 48 male rats. On the 5th postoperative day the rats were sacrificed and wound strength was measured by inserting a balloon into the abdomen and filling it with air until the abdomen burst. Pressure was measured in millimetres of mercury. Abdominal bursting pressure was 281.25 ± 26.5 mm Hg (mean ± SD) in the SIS group, 287.91 ± 29.6 mm Hg in the SCS group, 295.41 ± 31.9 mm Hg in the IDLC group and 314.58 ± 24.7 mm Hg in the CDLC group (P<0.05). Closure of the midline abdominal incisions using SCS has almost the same wound strength as SIS or IDLC but it is recommended because of simplicity, speed, and costs. CDLC ensures the greatest wound strength on the basis of the intraperi...
Collegium antropologicum, 2008
Subplate zone (SP) is prominent, transient laminar compartment of the human fetal cerebral wall. ... more Subplate zone (SP) is prominent, transient laminar compartment of the human fetal cerebral wall. The SP develops around 13 and gradually disappears after 32-34 postovulatory weeks. The SP neurons can be found as late as nine postnatal months, while remnants of the SP neurons can be traced until adult age in the form of interstitial neurons of the gyral white matter. SP is composed of postmigratory and migratory neurons, growth cones, loosely arranged axons, dendrites, glial cell and synapses. The remarkable feature of the SP is the presence of large amount of extracellular matrix. This feature can be used for delineation of SP in magnetic resonance images (MRI) of both, in vivo and post mortem brains. The importance of SP as the main synaptic zone of the human fetal cortex is based on the rich input of ,waiting,< afferents from thalamus and cortex, during the crucial phase of cortical target area selection. SP increases during mammalian evolution and culminates in human brain con...
Seminars in Fetal and Neonatal Medicine, 2006
We have correlated data on neuroanatomical organization and magnetic resonance imaging of transie... more We have correlated data on neuroanatomical organization and magnetic resonance imaging of transient fetal zones shown to contain connectivity elements (growing axons, synapses, dendrites). In the fetal phase, afferent fibres &amp;amp;amp;amp;amp;amp;#39;wait&amp;amp;amp;amp;amp;amp;#39; within the subplate zone which is the most prominent lamina on histological and magnetic resonance images and is a substrate of endogenous neuronal activity. In early preterm the thalamocortical afferents accumulate within the superficial subplate and grow into cortical plate developing synapses. In late preterm, the resolution of the subplate and growth of cortico-cortical fibres into the cortical plate occur simultaneously with gyration. Both preterm phases characterize the coexistence of endogenous and sensory-driven circuitries and occurrence of the transient electrical phenomena. In neonates, the long cortico-cortical pathways stop growth, and the main histogenetic events are an elaboration of intracortical circuitry and synaptogenesis. In conclusion, the growth of the axonal pathways preterm explains their vulnerability and plasticity. In neonates the vulnerability is related to the intracortical circuitry.
Collegium antropologicum, 2006
The corpus callosum connects two cerebral hemispheres as the most voluminous fiber system in the ... more The corpus callosum connects two cerebral hemispheres as the most voluminous fiber system in the human brain. The developing callosal fibers originate from immature pyramidal neurons, grow through complex pathways and cross the midline using different substrates in transient fetal structures. We analyzed cellular structures in the human corpus callosum on postmortem brains from the age of 18 weeks post conception to adult, using glial fibrillary acidic protein, neuron-specific nuclear protein, and chondroitin sulphate immunocytochemistry. We found the presence of transient cellular structures, callosal septa, which divide major fiber bundles and ventrally merge with subcallosal zone forming grooves for callosal axons. The callosal septa are composed of glial fibrillary acidic protein reactive meshwork, neurones and the chondroitin sulphate immunoreactive extracellular matrix. The developmental window of prominence of the callosal septa is between 18-34 weeks post conception which co...
Nekrotizirajući enterokolits najčešće je životno ugrožavajuće stanje gastrointestinalnog sustava ... more Nekrotizirajući enterokolits najčešće je životno ugrožavajuće stanje gastrointestinalnog sustava kod novorođenčadi, a primarno pogađa nedonoščad. To je bolest karakterizirana ishemičnom nekrozom crijevne sluznice. Patogeneza ove bolesti je još uvijek nerazjašnjena, ali se smatra da je multifaktorijalno uvjetovana. Važan mehanizam u nastanku je hiperreaktivni upalni odgovor nezrelog imunološkog sustava na ozljedu, u kojem se aktivira kaskada brojnih upalnih medijatora.To vodi ka povećanoj propusnosti crijeva i abnormalnoj bakterijskoj kolonizaciji. Kliničku sliku karakterizira nagla promjena u toleranciji enteralne prehrane, što se može prezentirati raznim abdominalnim i nespecifičnim simptomima. Također, vrijeme pojave simptoma može pomoći u diferencijalnoj dijagnozi, budući da pokazuje obrnutu povezanost s gestacijskom dobi. Težina NEK-a definirana je Bellovim kriterijima, a ovisno o težini kliničke slike i radiološkim nalazima. Dijagnoza se temelji na prisutnosti karakterističnih ...
Progress in Brain Research, 2014
The neural extracellular matrix (ECM) provides a supportive framework for differentiating cells a... more The neural extracellular matrix (ECM) provides a supportive framework for differentiating cells and their processes and regulates morphogenetic events by spatially and temporally relevant localization of signaling molecules and by direct signaling via receptor and/or coreceptor-mediated action. The embryonic human brain and fetal human brain contain large amounts and a diversity of extracellular matrix components, which are especially prominent in the transient subplate zone, in the crossroads of axonal pathways, at the developing cortical-white matter interface, and in the marginal zone. Perinatal and postnatal reorganizations of these tissue compartments extend into the second year of life. Developmental changes in the amount and composition of the extracellular matrix (as well as changes in fiber architectonics) are significant for plastic responses to damage and for changes in magnetic resonance imaging (MRI) signal intensity of the fetal and early postnatal human brain. In this chapter, we discuss the expression pattern of the major components of the fetal ECM of the human brain and the role they play during laminar and connectivity development in healthy brain and in the neurodevelopmental disorders. The aim of the chapter is to elucidate ECM-related developmental events as potential models of successful functional recovery after injury and to explore its relevance for diagnostic and therapeutic approaches.
ENCODS 2021 - Book of abstracts, 2021
Background: A considerable number of depressed women continue to use 5-hydroxytryptamine (5-HT) t... more Background: A considerable number of depressed women continue to use 5-hydroxytryptamine (5-HT) targeted antidepressants throughout pregnancy. The immediate 5-HT precursor, 5-hydroxytryptophan (5-HTP), is being increasingly offered as a natural and safer alternative to antidepressant medication. However, consequences of developmental exposure to increased 5-HTP concentrations on brain development and behaviour have not been studied in animal models or humans. During the perinatal period, 5- HT acts as a modulator of neural development. Growing evidence suggests the role of 5-HT, originating from the dorsal raphe nuclei (DRN), in the formation of the barrel field in the rodent somatosensory cortex. Topographically organized barrels, contained within the posteromedial barrel subfield (PMBS), represent the major facial whiskers, which rodents use to explore their environment. Methods and Findings: We examined consequences of perinatal treatment of Wistar rats with 25 mg/kg 5-HTP, from ...
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Papers by Natasa Jovanov Milosevic