Electron Microscopic Analysis of Hippocampal Axo-Somatic Synapses in a Chronic Stress Model for Depression.

Stress can alter the number and morphology of excitatory synapses in the hippocampus, but nothing is known about the effect of stress on inhibitory synapses. Here, we used an animal model for depression, the chronic mild stress model, and quantified the number of perisomatic inhibitory neurons and their synapses. We found reduced density of parvalbumin-positive (PV+) neurons in response to stress, while the density of cholecystokinin-immunoreactive (CCK+) neurons was unaffected. We did a detailed electron microscopic analysis to quantify the frequency and morphology of perisomatic inhibitory synapses in the hippocampal CA1 area. We analyzed 1100 CA1 pyramidal neurons and 4800 perisomatic terminals in five control and four chronically stressed rats. In the control animals we observed the following parameters: Number of terminals/soma = 57; Number of terminals/100 µm cell perimeter = 10; Synapse/terminal ratio = 32%; Synapse number/100 terminal = 120; Average terminal length = 920nm. None of these parameters were affected by the stress exposure. Overall, these data indicate that despite the depressive-like behavior and the decrease in the number of perisomatic PV+ neurons in the light microscopic preparations, the number of perisomatic inhibitory synapses on CA1 pyramidal cells was not affected by stress. In the electron microscope, PV+ neurons and the axon terminals appeared to be normal and we did not find any apoptotic or necrotic cells. This data is in sharp contrast to the remarkable remodeling of the excitatory synapses on spines that has been reported in response to stress and depressive-like behavior. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

A quinazoline-derivative compound with PARP inhibitory effect suppresses hypertension-induced vascular alterations in spontaneously hypertensive rats.

AIMS: Oxidative stress and neurohumoral factors play important role in the development of hypertension-induced vascular remodeling, likely by disregulating kinase cascades and transcription factors. Oxidative stress activates poly(ADP-ribose)-polymerase (PARP-1), which promotes inflammation and cell death. We assumed that inhibition of PARP-1 reduces the hypertension-induced adverse vascular changes. This hypothesis was tested in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: Ten-week-old male SHRs and wild-type rats received or not 5mg/kg/day L-2286 (a water-soluble PARP-inhibitor) for 32 weeks, then morphological and functional parameters were determined in their aortas. L-2286 did not affect the blood pressure in any of the animal groups measured with tail-cuff method. Arterial stiffness index increased in untreated SHRs compared to untreated Wistar rats, which was attenuated by L-2286 treatment. Electron and light microscopy of aortas showed prominent collagen deposition, elevation of oxidative stress markers and increased PARP activity in SHR, which were attenuated by PARP-inhibition. L-2286 treatment decreased also the hypertension-activated mitochondrial cell death pathway, characterized by the nuclear translocation of AIF. Hypertension activated all three branches of MAP-kinases. L-2286 attenuated these changes by inducing the expression of MAPK phosphatase-1 and by activating the cytoprotective PI-3-kinase/Akt pathway. Hypertension activated nuclear factor-kappaB, which was prevented by PARP-inhibition via activating its nuclear export. CONCLUSION: PARP-inhibition has significant vasoprotective effects against hypertension-induced vascular remodeling. Therefore, PARP-1 can be a novel therapeutic drug target for preventing hypertension-induced vascular remodeling in a group of patients, in whom lowering the blood pressure to optimal range is harmful or causes intolerable side effects.

Development of parvalbumin-immunoreactive neurons in the postnatal human hippocampal formation.

Introduction: Parvalbumin (PV) is a calcium-binding protein present in fast-spiking GABAergic neurons, such as basket and axo-axonic cells. Previous studies in non-human primates reported prenatal expression of PV in the temporal archicortex including entorhinal cortex and hippocampal formation. In contrast, PV-immunoreactivity was observed only postnatally in the human entorhinal cortex. Regarding PV expression in the human hippocampal formation, no information is available. Methods: In this study, the neurochemical maturation of PV-immunoreactive interneurons was studied in the postnatal developing human hippocampal formation. Results: Before birth, no PV-immunoreactive neurons could be detected in the human hippocampus. At birth, only a few PV-immunoreactive neurons were visible in Ammon's horn. The first PV-immunoreactive cells in the hilus of the dentate gyrus appeared at the age of 1 month. Even at the age of 5 months, only a few PV-immunopositive cells were present in the dentate hilus. The number of cells and their dendritic and axonal arborization in Ammon's horn and in the dentate gyrus gradually increased with age. Even at the age of 2 years, dendritic tree and axons of PV-immunoreactive neurons were less complex than can be seen in 8 and 11 years old children. Discussion: Our results showed that long-lasting maturation of PV-immunoreactive interneurons follows the developmental sequence of the subfields of the human hippocampal formation and provides further morphological evidence for the long-lasting functional maturation of the human cortex.

Vesicular zinc regulates the Ca2+ sensitivity of a subpopulation of presynaptic vesicles at hippocampal mossy fiber terminals.

Synaptic vesicles segregate into functionally diverse subpopulations within presynaptic terminals, yet there is no information about how this may occur. Here we demonstrate that a distinct subgroup of vesicles within individual glutamatergic, mossy fiber terminals contain vesicular zinc that is critical for the rapid release of a subgroup of synaptic vesicles during increased activity in mice. In particular, vesicular zinc dictates the Ca(2+) sensitivity of release during high-frequency firing. Intense synaptic activity alters the subcellular distribution of zinc in presynaptic terminals and decreases the number of zinc-containing vesicles. Zinc staining also appears in endosomes, an observation that is consistent with the preferential replenishment of zinc-enriched vesicles by bulk endocytosis. We propose that functionally diverse vesicle pools with unique membrane protein composition support different modes of transmission and are generated via distinct recycling pathways.

Effect of Air-Polishing and Different Post-Polishing Methods on Surface Roughness of Nanofill and Microhybrid Resin Composites.

Air-abrasion is a popular prophylactic procedure to maintain oral hygiene. However, depending on the applied air-abrasive powder, it can damage the surface of the tooth and restorations, making it susceptible to plaque accumulation. The purpose of this study was to investigate the effect of 5 s and 10 s air-abrasion of calcium carbonate on surface roughness (Ra) of enamel, nanofill, and microhybrid resin-composites and the effect of post-polishing with two-step rubber- (RP) or one-step brush polisher (BP) to re-establish the surface smoothness. Surface topography was visualized by scanning-electron-microscopy. The quantitative measurement of the Ra was carried out with atomic-force-microscopy. Air-abrasion for 10 s decreased the Ra of enamel as a result of abrasion of the natural surface texture. Post-polishing with RP after 10 s air-abrasion did not change the Ra or BP; however, Ra was increased significantly by scratching the surface. Air-abrasion increased the Ra of resin composites significantly, irrespective of the application time. While RP provided a similarly smooth surface to the control in the case of microhybrid resin composite, BP increased the Ra significantly. The Ra for the control group of the nanofill-resin composite was initially high, which was further increased by air-abrasion. RP and BP re-established the initial Ra with deeper and shallower scratches after BP. Both the material and treatment type showed a large effect on Ra.

Investigation of synapses in the cortical white matter in human temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common focal pharmacotherapy-resistant epilepsy in adults. Previous studies have shown significantly higher numbers of neurons in the neocortical white matter in TLE patients than in controls. The aim of this work was to investigate whether white matter neurons are part of the neuronal circuitry. Therefore, we studied the distribution and density of synapses in surgically resected neocortical tissue of pharmacotherapy-resistant TLE patients. Neocortical white matter of temporal lobe from non-epileptic patients were used as controls. Synapses and neurons were visualized with immunohistochemistry using antibodies against synaptophysin and NeuN, respectively. The presence of synaptophysin in presynaptic terminals was verified by electron microscopy. Quantification of immunostaining was performed and the data of the patients' cognitive tests as well as clinical records were compared to the density of neurons and synapses. Synaptophysin density in the white matter of TLE patients was significantly higher than in controls. In TLE, a significant correlation was found between synaptophysin immunodensity and density of white matter neurons. Neuronal as well as synaptophysin density significantly correlated with scores of verbal memory of TLE patients. Neurosurgical outcome of TLE patients did not significantly correlate with histological data, although, higher neuronal and synaptophysin densities were observed in patients with favorable post-surgical outcome. Our results suggest that white matter neurons in TLE patients receive substantial synaptic input and indicate that white matter neurons may be integrated in epileptic neuronal networks responsible for the development or maintenance of seizures.

Etiology-related Degree of Sprouting of Parvalbumin-immunoreactive Axons in the Human Dentate Gyrus in Temporal Lobe Epilepsy.

In the present study, we examined parvalbumin-immunoreactive cells and axons in the dentate gyrus of surgically resected tissues of therapy-resistant temporal lobe epilepsy (TLE) patients with different etiologies. Based on MRI results, five groups of patients were formed: (1) hippocampal sclerosis (HS), (2) malformation of cortical development, (3) malformation of cortical development + HS, (4) tumor-induced TLE, (5) patients with negative MRI result. Four control samples were also included in the study. Parvalbumin-immunoreactive cells were observed mostly in subgranular location in the dentate hilus in controls, in tumor-induced TLE, in malformation of cortical development and in MR-negative cases. In patients with HS, significant decrease in the number of hilar parvalbumin-immunoreactive cells and large numbers of ectopic parvalbumin-containing neurons were detected in the dentate gyrus' molecular layer. The ratio of ectopic/normally-located cells was significantly higher in HS than in other TLE groups. In patients with HS, robust sprouting of parvalbumin-immunoreactive axons were frequently visible in the molecular layer. The extent of sprouting was significantly higher in TLE patients with HS than in other groups. Strong sprouting of parvalbumin-immunoreactive axons were frequently observed in patients who had childhood febrile seizure. Significant correlation was found between the level of sprouting of axons and the ratio of ectopic/normally-located parvalbumin-containing cells. Electron microscopy demonstrated that sprouted parvalbumin-immunoreactive axons terminate on proximal and distal dendritic shafts as well as on dendritic spines of granule cells. Our results indicate alteration of target profile of parvalbumin-immunoreactive neurons in HS that contributes to the known synaptic remodeling in TLE.

[Postoperative outcome of surgical interventions for epilepsy between 2005 and 2016 at the Epilepsy Center of Pécs]. / Epilepsziasebészeti beavatkozások eredményei a Pécsi Epilepszia Centrumban 2005 és 2016 között.

INTRODUCTION: Epilepsy as a chronic, severe neurologic disease significantly influences the quality of life of the epileptic patients. In candidates well selected for surgery, the seizure freedom is realistically achievable, and the quality of life can be further improved with complex individual rehabilitation. AIM: We aimed to evaluate the postoperative outcome of patients who underwent epilepsy surgery between 2005 and 2016 at the Epilepsy Center at Pécs. METHOD: We evaluated seizure status at regular follow-up visits after surgery and the quality of life using questionnaires focusing on employment and social status. RESULTS: 76% of the 72 patients who underwent surgical resection for epilepsy were free from disabling seizures , and 10% had rare disabling seizures (almost seizure-free), 7% experienced worthwhile improvement and 7% had no worthwhile improvement. Comparing the employment status of patients free from disabling seizures to patients not free from disabling seizures, we found that the employment status is significantly influenced by seizure freedom (p<0.01, Fisher's exact test). While 67% of seizure-free patients were employed, only 19% of patients not free from disabling seizures were hired. CONCLUSION: Our results resemble the international tendencies and success rate, proving epilepsy surgery as an available, valid and effective treatment in well selected patients. Orv Hetil. 2019; 160(7): 270-278.

Calretinin expression in hilar mossy cells of the hippocampal dentate gyrus of nonhuman primates and humans.

Mossy cells, the major excitatory neurons of the hilus of the dentate gyrus constitutively express calretinin in several rodent species, including mouse and hamster, but not in rats. Several studies suggest that mossy cells of the monkey dentate gyrus are calretinin-positive, but others have reported mossy cells in monkeys to be devoid of detectable calretinin-like immunoreactivity. In the present study, the hilar region was investigated throughout the entire longitudinal extent of the hippocampal dentate gyrus in both Old World and New World monkeys, as well as in humans. In the examined four monkey species, mossy cells were found to be calretinin-positive at the uncal pole and at variable length within the main body of the dentate gyrus but not in the tail part. The associational pathway, formed by axons of mossy cells in the inner dentate molecular layer was calretinin-positive in more caudal sections, suggesting that mossy cell axon terminals may contain calretinin, whereas mossy cell somata may contain calretinin in a concentration too low to be detected by immunocytochemistry. In contrast, human mossy cells appear to be devoid of calretinin immunoreactivity in both their somata and their axon terminals. Taken together, mossy cells of nonhuman primates and humans exhibit different expression pattern for calretinin whereas they show similarities in neurochemical content, such as the cocaine and amphetamine-related transcript peptide.

A correlative light and electron microscopic study of postnatal myelination in the murine corpus callosum.

Oligodendroglial cells differ in their ultrastructural appearance depending on their myelin producing and maintaining activity. To better understand the relationship between light and electron microscopic features of myelination, myelin formation in the corpus callosum was studied in young postnatal mice. Immunostaining for myelin basic protein (MBP), which has an important role in myelin compaction, was compared with conventional Luxol Fast Blue myelin staining and with electron microscopic images of unlabeled tissue. MBP-immunostaining labeled a few oligodendroglial cells at postnatal day (P)3, and a few axons at P7 in the corpus callosum, below the fronto-parietal somatosensory cortex. By P10 there were more myelinated axons below the somatosensory cortex and the first MBP-immunoreaction appeared in the cingulum: labeling appeared even later in the remaining areas of corpus callosum. Electron microscopy revealed numerous medium oligodendroglial cells at P7 in the corpus callosum, below the somatosensory cortex with the first sign of myelination at P10. By P14, there were numerous myelin sheaths with loosely built structure, and the number of myelin sheaths increased continuously thereafter. However, even as late as P28, the presence of both thick, compact and thin, loosely structured myelin sheaths in the same section suggested ongoing myelination. With Luxol Fast Blue myelin staining was first observed in the corpus callosum relatively late, at P14. Areal differences in myelination of the corpus callosum, seen with MBP-immunohistochemistry, indicate that myelin formation follows cortical maturation rather than the rostro-caudal developmental growth of the corpus callosum. Myelination of the afferent and efferent fibers within the cortical areas seems to follow the inside-out maturational pattern of cortical neurons, with the first myelinated axons always appearing in layers V-VI. In addition to the known neuronal and astroglial factors that regulate myelin formation by oligodendroglial cells, we suggest that these cells and their myelin covering may also influence axonal maturation. Light microscopic data obtained with MBP-immunohistochemistry correlates well with electron microscopic observations but not with Luxol Fast Blue staining which reveals myelinated axons only relatively late in development. Therefore, both MBP-immunostaining and electron microscopy are useful, alone or in combination, for the detection of myelination, demyelination as well as remyelination processes in animal models and also in humans.

Evidence for the expression of parathyroid hormone 2 receptor in the human brainstem.

BACKGROUND AND PURPOSE: The parathyroid hormone 2 receptor (PTH2R) is a G protein coupled receptor. Pharmacological and anatomical evidence suggests that the recently identified tuberoinfundibular peptide of 39 residues is, and parathyroid hormone and parathyroid hormone-related peptide are not, its endogenous ligand. Initial functional studies suggest that the PTH2R is involved in the regulation of viscerosensory information processing. As a first step towards clinical applications, herein we describe the presence of the PTH2R in the human brainstem. MATERIAL AND METHODS: Total RNA was isolated from postmortem human cortical and brainstem samples for RT-PCR. Good quality RNA, as assessed on formaldehyde gel, was reverse transcribed. The combined cDNA products were used as template in PCR reactions with primer pairs specific for the human PTH2R. In addition, PTH2R immunolabelling was performed on free floating sections of the human medulla oblongata using fluorescent amplification immunochemistry. RESULTS: Specific bands in the RT-PCR experiments and sequencing of PCR products demonstrated the expression of PTH2R mRNA in the human brainstem. A high density of PTH2R-immunoreactive fibers was found in brain regions of the medulla oblongata including the nucleus of the solitary tract, the spinal trigeminal nucleus, and the dorsal reticular nucleus of the medulla. CONCLUSION: Independent demonstration of the presence of PTH2R mRNA and immunoreactivity supports the specific expression of the PTH2R in the human brainstem. The distribution of PTH2R-immunoreactive fibers in viscerosensory brain regions is similar to that reported in mouse and rat suggesting a similar role of the PTH2R in human as in rodents. This finding will have important implications when experimental data obtained on the function of the TIP39-PTH2R neuromodulator system in rodents are to be utilized in human.

Comparative anatomy of the hippocampal dentate gyrus in adult and developing rodents, non-human primates and humans.

There has been substantial progress in our understanding of the hippocampus in the past 70 years. During this time, it has become clear that the hippocampus is not an olfactory-related structure alone, but plays critical roles in other functions that do not necessarily depend on olfaction, such as learning and memory. In addition, it has become clear how important the hippocampus is to a wide variety of neurological disorders and psychiatric illness. Animal models have provided a great resource in such studies, but a frequent question is whether the data from laboratory animals is relevant to man.

Unaltered development of the archi- and neocortex in prematurely born infants: genetic control dominates in proliferation, differentiation and maturation of cortical neurons.

The development of cerebral cortex includes highly organized, elaborate and long-lasting series of events, which do not come to an end by the time of birth. Indeed, many developmental events continue after the 40th postconceptual week resulting in a long morphological, behavioral and cognitive development of children. Premature birth causes an untimely dramatic change in the environment of the human fetus and often results in serious threats for life. Cognitive abilities of prematurely born children vary, but a correlation between cognitive impairment and the time of birth is evident. In this study we review the morphological evidence of cortical maturation in preterm and full-term infants. Various aspects of postnatal cortical development including cell proliferation and maturation of neurons in the temporal archi- and neocortex are discussed and compared in preterm infants and age-matched full-term controls. Our results suggest that cell proliferation and maturation are not influenced by the preterm delivery. In contrast, the perinatal decrease of the number of Cajal-Retzius cells might be regulated by a mechanism that is affected by preterm birth. We demonstrate that cognitive deficiencies of the prematurely born infants cannot be explained with light microscopically observed alteration of proliferation and maturation of neurons.

Ontogeny of cocaine- and amphetamine-regulated transcript (CART) peptide and calbindin immunoreactivity in granule cells of the dentate gyrus in the rat.

Cocaine- and amphetamine-regulated transcript (CART) peptide was first discovered in the rat striatum following cocaine and amphetamine administration. However, even without psychostimulant treatment, many neuronal groups of the central nervous system, including granule cells of the dentate gyrus, express CART peptide. Earlier studies, based on the prenatal expression of CART peptide in the mesencephalon, suggest that it exerts neurotrophic effects. In the present study, ontogenetic expression of CART peptide in dentate gyrus granule cells was studied using immunohistochemistry in rats from 5 days to 3 months old. Expression was correlated with the expression of another neurochemical marker of granule cells, the calcium binding protein, calbindin. Calbindin was already present in granule cells at postnatal day 5 (P5), whereas CART peptide was first observed at P12. The first CART peptide- and calbindin-immunoreactive cells were localized to the lateral end of the dorsal blade, to the outer part of granule cell layer adjacent to the molecular layer, which agrees with the localization of the first-generated granule cells in the dentate gyrus. The first calbindin-immnunoreactive mossy fibers were seen at P9 in the stratum lucidum of CA3, and the entire projection path of mossy fibers expressed calbindin at P18. Mossy fibers were CART peptide-immunopositive at P12, and they were visible in the most distal part of CA3, in CA3a next to CA2. This localization fits with the known spatial organization of mossy fiber axon terminals. An adult-like expression of CART peptide and calbindin in the hippocampal formation was detectable at P30. The late postnatal appearance of CART peptide in dentate granule cells, and their axonal terminals, indicates that CART peptide may play a neurotrophic role in late developmental events, such as synaptogenesis. However, this does not exclude the possibility of a neuromodulatory role for this peptide.

Fetal development of membrane water channel proteins aquaporin-1 and aquaporin-4 in the human brain.

Aquaporin-1 and aquaporin-4, water channel membrane proteins reported in both experimental animals and in adult humans, have been detected in different, non-overlapping areas of the central nervous system. This immunohistochemical study describes the developmental expression pattern of the water channel membrane proteins, aquaporin-1 and aquaporin-4, in various structures of human fetal brain over the gestational period of 14-40 weeks. Aquaporin-1 immunostaining was exclusively found in the epithelial cells of the choroid plexus from the 14th gestational week, and the staining pattern altered slightly over time. At week 14, immunostaining appeared only in the apical cell membranes. By the 18th gestational week, the entire plasma membrane of these apical cells was immunopositive, as well as was the cytosol. These changes in immunoreactivity indicate an increasing production of aquaporin-1 in the epithelial cells during the period between the 14th and 24th weeks of gestation. Aquaporin-4 immunostaining was first detected in the archicortex, from gestational week 14 and was detected in the neocortex, 6-7 weeks later. Immunostained structures were always astrocytes, particularly the astrocytic endfeet in the ventricular wall, at the developing ependymal lining, at the pial surface, and around the capillaries. Neuronal labeling was not observed. These results in human fetal brain lend morphological support to the previous findings that aquaporin-1 and aquaporin-4 play different roles in the regulation of the water homeostasis of the brain.

Characterization of neurons in the cortical white matter in human temporal lobe epilepsy.

The aim of the present work was to characterize neurons in the archi- and neocortical white matter, and to investigate their distribution in mesial temporal sclerosis. Immunohistochemistry and quantification of neurons were performed on surgically resected tissue sections of patients with therapy-resistant temporal lobe epilepsy. Temporal lobe tissues of patients with tumor but without epilepsy and that from autopsy were used as controls. Neurons were identified with immunohistochemistry using antibodies against NeuN, calcium-binding proteins, transcription factor Tbr1 and neurofilaments. We found significantly higher density of neurons in the archi- and neocortical white matter of patients with temporal lobe epilepsy than in that of controls. Based on their morphology and neurochemical content, both excitatory and inhibitory cells were present among these neurons. A subset of neurons in the white matter was Tbr-1-immunoreactive and these neurons coexpressed NeuN and neurofilament marker SMI311R. No colocalization of Tbr1 was observed with the inhibitory neuronal markers, calcium-binding proteins. We suggest that a large population of white matter neurons comprises remnants of the subplate. Furthermore, we propose that a subset of white matter neurons was arrested during migration, highlighting the role of cortical maldevelopment in epilepsy associated with mesial temporal sclerosis.

The Harvard organic photovoltaic dataset.

The Harvard Organic Photovoltaic Dataset (HOPV15) presented in this work is a collation of experimental photovoltaic data from the literature, and corresponding quantum-chemical calculations performed over a range of conformers, each with quantum chemical results using a variety of density functionals and basis sets. It is anticipated that this dataset will be of use in both relating electronic structure calculations to experimental observations through the generation of calibration schemes, as well as for the creation of new semi-empirical methods and the benchmarking of current and future model chemistries for organic electronic applications.

NOS-positive local circuit neurons are exclusively axo-dendritic cells both in the neo- and archi-cortex of the rat brain.

Neuronal nitric oxide synthase (nNOS)-containing neurons and axon terminals were examined in the rat somatosensory and temporal neocortex, in the CA3/a-c areas of Ammon's horn and in the hippocampal dentate gyrus. In these areas, only nonpyramidal neurons were labeled with the antibody against nNOS. Previous observations suggested that all nNOS-positive nonpyramidal cells are GABAergic local circuit neurons, which form exclusively symmetric synapses. In agreement with this, nNOS-positive axon terminals in the hippocampal formation formed symmetric synapses exclusively with dendritic shafts. In the neocortex, in contrast, in addition to the nNOS-positive axon terminals that formed synapses with unlabeled spiny and aspiny dendrites and with nNOS-positive aspiny dendrites, a small proportion of the nNOS-positive axon terminals formed symmetric synapses with dendritic spines. These results suggest that nNOS-positive local circuit neurons form a distinct group of axo-dendritic cells displaying slightly different domain specificity in the archi- and neocortex. However, nNOS-positive cells show no target selectivity, because they innervate principal cells and local circuit neurons. Afferents to the NOS-positive cells display neither domain nor target selectivity, because small unlabeled terminals formed synapses with both the soma or dendrites of nNOS-positive neurons and an adjacent unlabeled dendrite or spine in both the hippocampal formation and in neocortex.

Cell proliferation correlates with the postconceptual and not with the postnatal age in the hippocampal dentate gyrus, temporal neocortex and cerebellar cortex of preterm infants.

BACKGROUND: In previous studies, lower IQ scores and educational difficulties of preterm children were correlated with the reduced size of several brain areas, including the cerebellum and the hippocampus. The most plausible reason for reduction would be the reduced cell formation following premature birth. However, no data are available about the rate of postnatal cell proliferation in the different brain areas of preterms. METHODS: Cytoarchitectonics and cell proliferation were examined in the cerebellum, hippocampal formation and temporal neocortex of preterm infants who lived for several weeks or months. Cell proliferation was detected with Ki-67 immunostaining and proliferating cells were identified with vimentin as glial and with CD31 and periodic acid-Schiff (PAS) reaction as endothelial elements. RESULTS: The rate of cell formation and the width of the cytoarchitectonic layers of the cerebellum of preterm infants corresponded to that of the age-matched controls. In the hippocampal dentate gyrus, the rate of cell formation and the density of proliferating cells were slightly higher in the preterm infants than in the full-term age-matched controls. Endothelial cell proliferation and the surface area of the capillaries were larger in the dentate gyrus of preterms than in age-matched controls. CONCLUSION: Rate of cell proliferation that correlates with the postconceptual age is not reduced in preterms, therefore the reduced size of the cerebellum and hippocampal formation is unlikely to be the result of decreased cell formation.

[Mitochondrial DNA deletions in newborn brain samples]. / Mitokondriális DNS-deletio vizsgálata újszülöttek agymintáiban.

INTRODUCTION: Mitochondrial DNA deletion affecting 4977 base pairs (mtDNA4977) thought to be the most common somatic mutation in man was analysed in samples taken from various parts of the brains at autopsy in order to analyse the supposition whether this mitochondrial damage may play a role in the causation of neurological dysfunction in childhood. METHODS: DNA was isolated from the samples of 15 newborns and 8 adults taken during autopsy. mtDNA4977 deletion was determined by polymerase chain reaction. RESULTS: mtDNA4977 could be demonstrated not only in adults but also in every newborn sample. Estimation of the amount of mtDNA4977 indicated that the level of mtDNA4977 was smaller in the newborn samples than in the elderly's. CONCLUSION: Results suggest that mtDNA4977, contrary to the generally accepted opinion stating that it is acquired during life span, may already be present in the beginning of life. However, the possibility can not be excluded that mutations in the extreme sensitive mtDNA against oxidative damage might be generated by perinatal hypoxia and intensive care. Such a causative role of mtDNA mutations may be an important additional factor in explaining the pathomechanism of cerebral palsy and mental retardation frequently observed in surviving children.