Subplate Zone of the Human Brain: Historical Perspective and New Concepts

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 concomitantly with increase in number and diversity of cortico-cortical fibers. The recent neurobiological evidence shows that SP is important site of spontaneous endogeneous activity, building a framework for development of cortical columnar organization. The SP, which can be readily visualized on conventional and DTI (diffusion-tensor-imaging) MRI in vivo, today is in the focus of interest of pediatric neurology due to the following facts: (1) SP is the site of early neural activity, (2) SP is the major substrate for functional plasticity, and (3) selective vulnerability of SP may lead to cognitive impairment

Neurological emergencies

Hitna stanja u neurologiji, s jedne strane zbog svoje velike učestalosti, a s druge zbog potrebe za što ranijim zbrinjavanjem i adekvatnom intervencijom u cilju spašavanja života i sprječavanja komplikacija, zauzimaju vrlo važnu ulogu u medicinskoj skrbi općenito. Pacijenti su često vitalno ugroženi te se velik broj njih nalazi u neurološkim jedinicama za intenzivno liječenje gdje je moguć adekvatan hemodinamski monitoring, procjena cerebralne perfuzije, oksigenacije i metabolizma nizom specifičnih pretraga (EEG, mjerenje intrakranijalnog tlaka, transkranijalni dopler). Klinička slika uključuje poremećaje svijesti, poremećaje funkcije kranijalnih živaca, mišićnu slabost, osjetne ispade, toničko-kloničke grčeve i mnoge druge. Najčešće hitno stanje u neurologiji svakako je cerebrovaskularni inzult koji se mora što ranije prepoznati u cilju liječenja i sprječavanja posljedica bolesti. Nagli nastanak simptoma karakterističan je za subarahnoidalno krvarenje kojem treba uslijediti što hitnije zbrinjavanje uzroka, prevencija ponovnog krvarenja te liječenje lokalnih i sistemskih komplikacija. Epileptički status, kao stanje kojem predležeći uzroci mogu biti vrlo raznoliki, u prvom redu zahtijeva prekid napadaja, prevenciju ponovnog javljanja istog, a tek potom zbrinjavanje uzroka i posljedica. Upalne poliradikuloneuropatije i miastenička kriza zahtijevaju brižan nadzor pacijenta zbog čestih popratnih autonomnih disfunkcija i mogućeg brzog i naglog pogoršanja stanja pacijenta. Uz pružanje odgovarajuće medicinske skrbi i njege, nužna je i psihološka potpora bolesnicima te fizikalna terapija s ciljem što bolje rehabilitacije.Neurological emergencies play an important role in the medical care due to its high incidence and the need of quick and adequate care. Neurological intensive care unit is an ideal place to address critically ill patients because it provides both standard interventions and hemodynamic monitoring as well as the specific care including monitoring of cerebral perfusion, oxygenation and metabolism via EEG, intracranial pressure, and transcranial doppler. The main symptoms associated with the neurological emergencies include impaired level of consciousness, cranial nerve dysfunction, muscle weakness, partial or complete loss of sensation, seizures etc. Cerebrovascular insult is the most common emergency that requires early recognition, management, and prevention of complications. The main aim for patients with subarachnoid haemorrhage is investigating the cause of the haemorrhage, prevention of early rebleeding and the management of local and systemic complications. The treatment of status epilepticus proceeds on termination of seizures, prevention of its recurrence, management of the underlying cause and complications. Acute polyradiculoneuritis and myasthenic crisis can cause sudden and rapid deterioration of health because they are often accompanied with autonomic instability. In addition to providing adequate medical care and physical therapy, we should also give our patients psychological support

Neurological emergencies

Hitna stanja u neurologiji, s jedne strane zbog svoje velike učestalosti, a s druge zbog potrebe za što ranijim zbrinjavanjem i adekvatnom intervencijom u cilju spašavanja života i sprječavanja komplikacija, zauzimaju vrlo važnu ulogu u medicinskoj skrbi općenito. Pacijenti su često vitalno ugroženi te se velik broj njih nalazi u neurološkim jedinicama za intenzivno liječenje gdje je moguć adekvatan hemodinamski monitoring, procjena cerebralne perfuzije, oksigenacije i metabolizma nizom specifičnih pretraga (EEG, mjerenje intrakranijalnog tlaka, transkranijalni dopler). Klinička slika uključuje poremećaje svijesti, poremećaje funkcije kranijalnih živaca, mišićnu slabost, osjetne ispade, toničko-kloničke grčeve i mnoge druge. Najčešće hitno stanje u neurologiji svakako je cerebrovaskularni inzult koji se mora što ranije prepoznati u cilju liječenja i sprječavanja posljedica bolesti. Nagli nastanak simptoma karakterističan je za subarahnoidalno krvarenje kojem treba uslijediti što hitnije zbrinjavanje uzroka, prevencija ponovnog krvarenja te liječenje lokalnih i sistemskih komplikacija. Epileptički status, kao stanje kojem predležeći uzroci mogu biti vrlo raznoliki, u prvom redu zahtijeva prekid napadaja, prevenciju ponovnog javljanja istog, a tek potom zbrinjavanje uzroka i posljedica. Upalne poliradikuloneuropatije i miastenička kriza zahtijevaju brižan nadzor pacijenta zbog čestih popratnih autonomnih disfunkcija i mogućeg brzog i naglog pogoršanja stanja pacijenta. Uz pružanje odgovarajuće medicinske skrbi i njege, nužna je i psihološka potpora bolesnicima te fizikalna terapija s ciljem što bolje rehabilitacije.Neurological emergencies play an important role in the medical care due to its high incidence and the need of quick and adequate care. Neurological intensive care unit is an ideal place to address critically ill patients because it provides both standard interventions and hemodynamic monitoring as well as the specific care including monitoring of cerebral perfusion, oxygenation and metabolism via EEG, intracranial pressure, and transcranial doppler. The main symptoms associated with the neurological emergencies include impaired level of consciousness, cranial nerve dysfunction, muscle weakness, partial or complete loss of sensation, seizures etc. Cerebrovascular insult is the most common emergency that requires early recognition, management, and prevention of complications. The main aim for patients with subarachnoid haemorrhage is investigating the cause of the haemorrhage, prevention of early rebleeding and the management of local and systemic complications. The treatment of status epilepticus proceeds on termination of seizures, prevention of its recurrence, management of the underlying cause and complications. Acute polyradiculoneuritis and myasthenic crisis can cause sudden and rapid deterioration of health because they are often accompanied with autonomic instability. In addition to providing adequate medical care and physical therapy, we should also give our patients psychological support

Prenatal Glucocorticoids: Short-Term Benefits and Long-Term Risks

Glucocorticoids are steroid hormones synthesized in the adrenal gland cortex, and most of their physiological effects are mediated by the glucocorticoid receptor (GR), that acts as a ligand-dependent transcription factor. Coordinate changes in metabolism under glucocorticoid influence provide energy that is instantly and selectively available to vital organs, an enables them to deal with immediate environmental demands, at the expense of anabolic pathways, such as bone formation, reproduction, immunological responses and other, that are being blunted or delayed, under glucocorticoid influence [1-3]. During fetal development the synthesis of adrenal glucocorticoids precedes the establishment of a definitive structure of the gland. In rats, secretion of the main glucocorticoid – corticosterone starts as early as on day 13 of development [4] (term=22 days, short gestation period), while in humans secretion of the main glucocorticoid – cortisol starts in the 8th week of pregnancy (term=40 weeks, long gestation period) [5]. Glucocorticoid receptor mRNA is present in the tissue derivatives of all three germ layers from fetal day 13 onwards, and increases gradually during rat fetal development [6]. Human fetal tissues express GR at the gestational age of 6 weeks, meaning that the machinery for hormone action is prepared at the early stages of development [5]. These facts suggest that endogenous glucocorticoids produced by the fetal adrenal glands have a crucial role in fetal growth and the development of individual fetal tissues [7]. In response to the prepartum rise in glucocorticoids a wide variety of changes known as “preparation for birth” occurs, meaning that the maturational changes in many fetal tissues, essential for neonatal survival, are intensified during the last third of gestation. Namely, circulating glucocorticoids induce fetal lung maturation and surfactant production, trigger a variety of physiological effects on brain cell differentiation and synaptogenesis, stimulate the production of hepatic gluconeogenic enzymes, affect pancreatic -cell development and insulin content, influence renal development and affect the maturation of the immune system [8-10]. Metabolic, cardiovascular and immune adaptations under glucocorticoid influence are fundamental to successfully overcoming birth-related stress and postnatal adaptation of the newborn to environmental challenges [11, 12]. Environmental conditions influence the prevailing nutritional and endocrine status in mothers and fetuses. Numerous animal and human studies have shown that adverse environmental conditions during pregnancy, such as maternal undernutrition [13, 14], stress [15, 16], illness, placental insufficiency [17, 18], as well as prenatal glucocorticoid exposure [19, 20] affect fetal development and postnatal outcome. Changes in the maternal hypothalamic-pituitary-adrenal (HPA) activity, transplacental diffusion of nutrients, hormones and growth factor supply, potently affect the fetal HPA axis influencing glucocorticoid output as well as other developing systems [21, 22]. Gestational age, at which an insult occurs, its nature and intensity, determines the specific tissue or organ which will be affected by the insult. Glucocorticoids are the key mediators between maternal environment and the fetus, and as such are involved in adaptations of the fetus to predicted postnatal environment. Even transient changes in glucocorticoid levels could have longlasting consequences. The outcome might be growth retardation and change in the developmental trajectory, in the direction that best suited to the expected environment [23, 24]. This phenomenon is known as programming. The adaptations caused by suboptimal intrauterine conditions are appropriate if the predicted and actual postnatal environments match, and lead to survival to reproduce in a deprived environment [25, 26]. If there is a mismatch between the environment predicted and the actual environment experienced postnatally, adaptations are inappropriate and result in the development of disease like hypertension, ischemic heart disease, glucose intolerance, insulin resistance and type 2 diabetes [27-29]. In this chapter the latest findings, with clear statements from the literature, as well as own results regarding the endocrine mechanisms of intrauterine programming mediated by glucocorticoids will be analyzed. The causal relationship between a prenatally programmed endocrine axes and their postnatal functioning that affect growth, stress response, metabolism and reproduction will be discussed. In order to better understand mechanisms of fetal glucocorticoid programming of endocrine axes, special attention will be paid to key points of their development

Quantitative Analysis of Basal Dendritic Tree of Layer IIIc Pyramidal Neurons in Different Areas of Adult Human Frontal Cortex

Large long projecting (cortico-cortical) layer IIIc pyramidal neurons were recently disclosed to be in the basis of cognitive processing in primates. Therefore, we quantitatively examined the basal dendritic morphology of these neurons by using rapid Golgi and Golgi Cox impregnation methods among three distinct Brodmann areas (BA) of an adult human frontal cortex: the primary motor BA4 and the associative magnopyramidal BA9 from left hemisphere and the Broca’s speech BA45 from both hemispheres. There was no statistically significant difference in basal dendritic length or complexity, as dendritic spine number or their density between analyzed BA’s. In addition, we analyzed each of these BA’s immunocytochemically for distribution of SMI-32, a marker of largest long distance projecting neurons. Within layer IIIc, the highest density of SMI-32 immunopositive pyramidal neurons was observed in associative BA9, while in primary BA4 they were sparse. Taken together, these data suggest that an increase in the complexity of cortico-cortical network within human frontal areas of different functional order may be principally based on the increase in density of large, SMI-32 immunopositive layer IIIc neurons, rather than by further increase in complexity of their dendritic tree and synaptic network

Neonataly applied SRIH-14 has immediate and prolonged inhibitory effect on pituitary GH cells

The immediate and prolonged effects of neonatal SRIH-14 treatment on pituitary somatotrophs (GH) were investigated. Female rats were injected s.c. twice a day with 20 _g of SRIH-14/100g b.w., for five consecutive days (from 3rd to 7th day of life). Animals were sacrificed at different life periods: at neonatal (8th day), juvenile (16th day), peripubertal (38th day) and adult (80th day) period of life. GH cells were studied using the peroxidase-antiperoxidase immunocytochemical procedure. Morphometry and stereology were used to evaluate changes in the number of GH-immunoreactive cells per unit area, their volume and volume density. After SRIH-14 treatment, the most prominent decrease of all measured parameters was observed in the neonatal period. SRIH-14 induced a significant decrease of GH cell volumes and volume densities in the juvenile, peripubertal and adult periods of life. The number of GH-positive cells was significantly decreased when examined immediately after treatment, but significantly increased in adult females. Body weight, absolute or relative pituitary weights were not affected in any of the examined age groups. These findings suggest that neonatal SRIH-14 treatment exerts a significant immediate and prolonged inhibitory effect on GH cells, but does not affect the growth rate in female rats.Ispitivan je neposredan i odložen efekat neonatalnog tretmana somatostatinom (SRIH-14) na somatotropne (GH) ćelije. Ženke pacova su dva puta dnevno s.c. tretirane sa 20 _g SRIH-14/100g t.m. u toku pet dana (od 3. do 7. dana života) i žrtvovane u različitim periodima života: u neonatalnom (8. dan) juvenilnom (16. dan), peripubertalnom (38. dan) i adultnom (80. dan) periodu. GH ćelije su imunocitohemijski obeležene metodom peroksidaza-antiperoksidaza a morfometrijskim i stereološkim metodama određivani su broj GH ćelija po jedinici površine, njihov volumen i volumenska gustina. Nakon somatostatinskog tretmana, najznačajnije smanjenje svih merenih parametara utvrđeno je u neonatalnom periodu. SRIH-14 je izazvao značajno smanjenje volumena i volumenske gustine GH ćelija u juvenilnom, peripubertalnom i adultnom periodu života. Broj GH-pozitivnih ćelija po mm2 je bio značajno smanjen kada je ispitivan neposredno nakon tretmana, ali je bio značajno povećan kod adultnih ženki. Telesna masa, kao i apsolutne i relativne mase hipofiza nisu bile izmenjene ni u jednoj od ispitivanih starosnih grupa. Dobijeni rezultati ukazuju da neonatalni tretman somatostatinom izaziva značajan neposredan i odložen inhibitoran uticaj na GH ćelije, ali ne utiče na stopu rasta kod ženki pacova.nul

Growth of the Human Corpus Callosum: Modular and Laminar Morphogenetic Zones

The purpose of this focused review is to present and discuss recent data on the changing organization of cerebral midline structures that support the growth and development of the largest commissure in humans, the corpus callosum. We will put an emphasis on the callosal growth during the period between 20 and 45 postconceptual weeks (PCW) and focus on the advantages of a correlated histological/magnetic resonance imaging (MRI) approach. The midline structures that mediate development of the corpus callosum in rodents, also mediate its early growth in humans. However, later phases of callosal growth in humans show additional medial transient structures: grooves made up of callosal septa and the subcallosal zone. These modular (septa) and laminar (subcallosal zone) structures enable the growth of axons along the ventral callosal tier after 18 PCW, during the rapid increase in size of the callosal midsagittal cross-section area. Glial fibrillary acidic protein positive cells, neurons, guidance molecule semaphorin3A in cells and extracellular matrix (ECM), and chondroitin sulfate proteoglycan in the ECM have been identified along the ventral callosal tier in the protruding septa and subcallosal zone. Postmortem MRI at 3 T can demonstrate transient structures based on higher water content in ECM, and give us the possibility to follow the growth of the corpus callosum in vivo, due to the characteristic MR signal. Knowledge about structural properties of midline morphogenetic structures may facilitate analysis of the development of interhemispheric connections in the normal and abnormal fetal human brain

Regional pattern of physical inactivity in Croatia [Regionalizam fizičke neaktivnosti u Hrvatskoj]

The aim of this paper was to analyze the regional pattern of physical inactivity in Croatia based on the Croatian Adult Health Survey 2003 data. A total of 9,070 adult respondents were included in this study. In men, the highest prevalence of physical inactivity was recorded in the City of Zagreb (39.6%), and it was significantly higher than in Central (25.6%), Coastal (25.6%) and Mountainous region (14.1%). Mountainous region had significantly lower prevalence of physical inactivity compared to any other region, except the Central region. The highest prevalence of physical inactivity in women was also recorded in the City of Zagreb (43.6%), and it was also significantly higher than in all other regions. The lowest prevalence of physical inactivity was recorded in Eastern Region (24.7%). The highest levels of physical inactivity in both in both genders were recorded in urban regions, suggesting that intervention measures in terms of health promotion should be undertaken, with strong emphasis on the people living in urban settings

Ionizing irradiation affect extracellular nucleotide hydrolysis in brain of rats in different stages of development: ii 30-day-old rats

The effect of acute gamma irradiation (IR) on enzyme activity of rat brain Ecto-Nucleotide Diphosphohydrolase (E-NTPDase), in presence of adenosine triand diphophashates (ATP and ADP) and divalent cations (Ca2+ and Mg2+), has been investigated. The aim of research was to study the influence of low (50 cGy) and therapeutic (2Gy) doses of whole-body irradiation on rat brain E-NTPDase enzyme activity 24h after treatment in prepubertal and adult rats. Our results suggest that whole-body irradiation could induce modulation of neural activity in rat brain, especially in young rats.Physical chemistry 2008 : 9th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 24-28 September 200

Development of pituitary ACTH and GH cells in near term rat fetuses

This study describes the development of ACTH and GH cells in 19- and 21-day-old rat fetuses using immunohistochemistry and morphometric measurements. Between days 19 and 21 of pregnancy, the total volume of fetal ACTH cells was unchanged, while their volume density and number per unit of area decreased significantly. ACTH-like immunopositivity in the pars intermedia increased during the examined period. The cell volume, volume density and number of GH cells per unit of area all markedly increased in parallel with fetal development, i.e., from gestational days 19 to 21. GH-like immunopositivity is demonstrated in the pars intermedia of 21-day-old fetuses for the first time.Prezentovano istraživanje opisuje razvoj ACTH i GH ćelija hipofize fetusa pacova, neposredno pred rođenje korišćenjem imunohistohemije i morfometrijskih merenja. Od 19. do 21. dana gestacije volumen ACTH ćelija fetusa bio je nepromenjen, dok su volumenska gustina i broj ćelija po jedinici površine značajno smanjeni. Intenzitet ACTH imunopozitivnosti u pars intermedia povećavn je tokom ispitivanog perioda. Volumen GH ćelija, volumenska gustina i brojnost po jedinici površine značajno su povećani tokom završnog perioda fetalnog razvoja, tj. od 19. do 21. dana gestacije. GH imunopozitivnost prvi put je demonstrirana u ćelijama pars intermedia kod fetusa starih 21 dan.nul