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PubMed1999

[Cortical thrombophlebitis and developmental venous anomalies].

Abnormal intracranial venous drainage called cerebral venous angioma is usually asymptomatic. Hemorrhages and seizures may however occur. The malformation may rarely be revealed by thrombosis. We report the case of a 25-year-old right-handed woman who developed cortical thrombophlebitis subsequent to developmental venous anomalies. After a course of anticoagulant therapy, outcome was good, demonstrating that anticoagulant therapy may be indicated in spite of the high risk of hemorrhage.

Adult↗
PubMed2002

Connexin expression in homotypic and heterotypic cell coupling in the developing cerebral cortex.

Intercellular communication through gap junction channels is a prominent feature of the developing cerebral cortex. In the first 2 weeks after birth, a time critical in the development of the rat neocortex, extensive cell coupling has been documented that diminishes as the cortex matures. Among the family of gap junction proteins, connexins 26, 36, and 43 are differentially expressed during cortical development. We used intracellular dye injections and connexin immunohistochemistry to investigate the coupling patterns and connexin expression between the different neuronal and glial cell types of the developing cortex of the rat. We found that neurons and glia couple homotypically and heterotypically at postnatal days 7 and 14. Although the prevalence of coupling was homotypic, there was considerable heterotypic coupling that involved pyramidal and nonpyramidal neurons, the principal neuronal cell types of the cortex, or neurons and astrocytes. Coupling between different cell types appeared to be mediated by differential expression of connexins 26, 36, and 43. It may be that coupling between cells in the developing neocortex is a function of the spatial and temporal expression of these and other connexin proteins.

Animals↗
PubMed1980

Cortical Air Spaces (Aerenchyma) in Roots of Corn Subjected to Oxygen Stress: STRUCTURE AND INFLUENCE ON UPTAKE AND TRANSLOCATION OF RUBIDIUM IONS.

When the seminal root system of 14-day-old corn (Zea mays cv. Dekalb 202) was subjected to O(2) stress, nodal roots with well developed cortical air spaces (aerenchyma) grew into the deoxygenated solution. Microscopic examination showed that there was extensive breakdown of cells in the midcortex of these roots, while the stele, endodermis, and inner layer of cortical cells remained complete, as did the outer layers of the cortex and the epidermis. Occasional files of intact cells, and the wall residues of collapsed cells, crossed the space between inner and outer cortex. Experiments with short, intact root segments with and without air spaces showed that in the presence of O(2) the ability to absorb and translocate (86)Rb(+), per unit volume or length of root, was little affected by cortical degeneration. The distribution across root sections of recently supplied strontium and rubidium, determined by electron microprobe analysis, indicated that in roots with air spaces the strands of wall residues bridging the cortex could be involved in maintaining the conduction of ions from the outer cortex up to the endodermis.

Journal Article↗
PubMed2005

Cognitive functioning in bilateral perisylvian polymicrogyria (BPP): clinical and radiological correlations.

Bilateral perisylvian polymicrogyria (BPP) is a malformation of cortical development, frequently associated with severe dysarthria or anarthria. BPP patients are therefore often labeled as severely retarded, but a detailed neuropsychological profile has not been reported to date. In a series of 14 patients, we demonstrated that only a minority had extremely low intelligence, and that some aspects of cognitive function correlated with the extent of the cortical disorganization. Early age at seizure onset correlated positively with Performance IQ scores (P<0.05) and negatively with the extent of the lesion (P<0.01), reflecting that patients with more severe BPP are more likely to have early seizure onset, resulting in greater interference with ongoing cognitive development. Receptive and expressive language skills were found to be equally poor. Frontal lobe function and memory abilities were relatively well preserved, suggesting that the observed cognitive profiles were related, at least in part, to specific areas of cortical dysfunction and not only to global dysfunction.

Adult↗
PubMedDate not supplied

Spacing of cytochrome oxidase blobs in visual cortex of normal and strabismic monkeys.

Some models of visual cortical development are based on the assumption that the tangential organization of V1 is not determined prior to visual experience. In these models, correlated binocular activity is a key element in the formation of visual cortical columns, and when the degree of interocular correlation is reduced the models predict an increase in column spacing. To examine this prediction we measured the spacing of columns, as defined by cytochrome oxidase (CO) blobs, in the visual cortex of monkeys whose binocular vision was either normal or disrupted by a strabismus. The spatial distribution of blobs was examined in seven normal and five strabismic macaques. Tangential sections through the upper layers of the visual cortex were stained to reveal the two-dimensional (2D) pattern of CO blobs. Each blob was localized and their center-to-center spacing, packing arrangement and density were calculated using 2D nearest-neighbor spatial analyses. The mean center-to-center spacing of blobs (590 microm for normally reared and 598 microm for strabismic macaques) and the mean density of blobs (3.67 blobs/mm2 for normally reared and 3.45 blobs/mm2 for strabismic macaques) were not significantly different. In addition, the 2D packing arrangement of the blobs was not affected by strabismus. While it is clear that neural activity plays a key role in the elaboration and refinement of ocular dominance cortical modules, we conclude that it does not determine the spatial period of the pattern of CO blobs. This suggests that aspects of the neural circuitry underlying the columnar architecture of the visual cortex are established prenatally and its fundamental periodicity is not modifiable by experience.

Animals↗
PubMed1999

Familial lissencephaly with cleft palate and severe cerebellar hypoplasia.

Lissencephaly is a brain malformation characterized by absence of gyral formation, resulting in a smooth brain surface. Histologic study shows severe anomalies of cerebral cortical development. Several lissencephaly syndromes have been described. Here we report a familial syndrome of lissencephaly, cleft palate, diffuse agyria, and severe cerebellar hypoplasia. Microscopic examination of the abnormally thick cerebral cortex showed absence of cortical layering, with preservation of the pia-glial barrier. This is the first report of recurrent lissencephaly with cleft palate and severe cerebellar hypoplasia in which these unique neuropathology findings are described. Autosomal recessive inheritance is suggested by recurrence in sibs within the same family, but germ cell mosaicism for a dominant mutation is not excluded.

Abnormalities, Multiple↗
PubMed2005

Assessment of cortical maturation with prenatal MRI. Part I: Normal cortical maturation.

Cortical maturation, especially gyral formation, follows a temporospatial schedule and is a good marker of fetal maturation. Although ultrasonography is still the imaging method of choice to evaluate fetal anatomy, MRI has an increasingly important role in the detection of brain abnormalities, especially of cortical development. Knowledge of MRI techniques in utero with the advantages and disadvantages of some sequences is necessary, in order to try to optimize the different magnetic resonance sequences to be able to make an early diagnosis. The different steps of cortical maturation known from histology represent the background necessary for the understanding of maturation in order to be then able to evaluate brain maturation through neuroimaging. Illustrations of the normal cortical maturation are given for each step accessible to MRI for both the cerebral hemispheres and the posterior fossa.

Brain↗
PubMed1991

Initial expression and endogenous activation of NMDA channels in early neocortical development.

We have made patch-clamp recordings from slices of fetal and postnatal rat neocortex in order to study the initial expression and activation of NMDA channels. Recordings from both whole cells and outside-out patches indicated that functional NMDA channels are expressed on neurons within the cortical plate, but not on younger cells within the ventricular zone. The NMDA channels on cortical plate neurons had a unitary conductance of approximately 40 pS, had a mean open time of approximately 6 msec, required glycine to open, and were blocked in a voltage-dependent manner by magnesium. These precocious channels were present before the appearance of functional synaptic activity, yet like NMDA channels in the mature neocortex, they were spontaneously activated by an agonist within brain slices. These results demonstrate that NMDA channels are initially expressed on neocortical neurons some time between the last mitotic division within the ventricular zone and completion of migration into the cortical plate. These early NMDA channels have properties characteristic of NMDA channels on more mature neurons and are similarly activated by an endogenous agonist in situ. Their early appearance and activation indicate that NMDA channels may play a role during early stages of cortical development.

Aging↗
PubMed2005

Cortical malformation and pediatric epilepsy: a molecular genetic approach.

Genetic malformations of the cerebral cortex are important causes of neurologic morbidity in children because they are often associated with developmental delay, motor disturbances (cerebral palsy), and epilepsy. Primary autosomal recessive microcephaly is a cortical malformation with a low incidence of epilepsy. One of its causative genes, ASPM, might play an important role in regulating proliferation of neuronal progenitor cells. Mutations in ASPM do not seem to affect later stages of cortical development, such as neuronal migration, and this might be responsible for the low epileptogenicity of this malformation. ASPM might also have played an important role in the evolutionary expansion of the human brain. Bilateral frontoparietal polymicrogyria, on the other hand, is a highly epileptogenic malformation. Its causative gene, GPR56, is also expressed in the neurogenic regions of the cortex, but its primary function might be in the determination of cell fate and/or cortical patterning. Further studies of these genes will likely lead to a better understanding of human brain development and epilepsy.

Cerebral Cortex↗
PubMed1980

The lipopigments in human brain tissue necroses. I. Ceroid.

The ceroid pigment of macrophages were subdivided into four different types according to their own color and their ability to stain with luxol fast blue. With reference to this mode a series of more than 200 brain infarcts which had happened 1 day to 56 years before death, was examined systematically. According to the results the ceroid variants do not only succeed one another chronologically but they also represent histochemically successive phases of development which correspond to the progressive auto-oxidation of unsaturated lipids. The occurrence of the different stages is chronologically defined. During this development cortical and subcortical macrophages show different speeds in the ageing process of their pigments. There is no evidence for an essential participation of proteins in the maturation of the ceroid. Not during any phase of development is the reaction pattern identical with that of neuronal and glial lipofuscin.

Cerebral Infarction↗
PubMed2005

Adjusting EEG coherence for inter-electrode distance effects: an exploration in normal children.

Electroencephalographic (EEG) coherence between two points is strongly related to the distance between them, being inflated by volume conduction effects at short distances and reduced by signal phase differences at larger distances. This precludes simple comparison of coherence estimates involving different inter-electrode distances. We investigated adjusting coherence measures to remove such distance effects. After subtracting the estimated effects of random coherence due to volume conduction, exponential regression of the reduced coherence values against measured inter-electrode distance was used to estimate the remaining effects of inter-electrode distance. Residuals from this procedure were taken as coherences corrected for the systematic distance effects. These were adjusted to the mean reduced coherence level to avoid complexities in conceptualising negative residual coherences. It was found that systematic inter-electrode distance effects accounted for more than 50% of the variance remaining after removal of random coherence estimates. After these were also removed, substantial effects of EEG frequency band, different regions of the brain, and interhemispheric versus intrahemispheric values, as well as laterality effects within the latter, were obtained. Regional and frequency differences in adjusted coherence appear to reflect patterns expected from normal cortical development, but detailed understanding of more complex interactive effects is limited by the lack of relevant developmental data. Adjusting coherence values to remove systematic variability due to inter-electrode distances better represents cortico-cortical coupling and allows more efficient statistical analysis. This may contribute towards a better integration of coherence data in the EEG exploration of both normal and atypical brain functioning.

Brain↗
PubMed2006

Magnetic resonance imaging of the fetal brain and spine: an increasingly important tool in prenatal diagnosis, part 1.

Fetal MR imaging is an increasingly available technique used to evaluate the fetal brain and spine. This is made possible by recent advances in technology, such as rapid pulse sequences, parallel imaging and advances in coil design. This provides a unique opportunity to evaluate processes that cannot be approached by any other current imaging technique and affords a unique opportunity for studying in vivo brain development and early diagnosis of congenital abnormalities inadequately visualized or undetectable by prenatal sonography. This 2-part review summarizes some of the latest developments in MR imaging of the fetal brain and spine and its application to prenatal diagnosis. This first part discusses the utility, safety, and technical aspects of fetal MR imaging, the appearance of normal fetal brain development, and the role of fetal MR imaging in the evaluation of fetal ventriculomegaly. The second part focuses on additional clinical applications of fetal MR imaging, including suspected abnormalities of the corpus callosum, malformations of cortical development, and spine abnormalities.

Brain↗
PubMed2000

Developmental changes in progenitor cell responsiveness to bone morphogenetic proteins differentially modulate progressive CNS lineage fate.

Although multipotent progenitor cells capable of generating neurons, astrocytes and oligodendrocytes are present within the germinal zones of the brain throughout embryonic, postnatal and adult life, the different neural cell types are generated within discrete temporospatial developmental windows. This might suggest that multipotent progenitor cells encounter different signals during each developmental stage, thus accounting for separate waves of lineage commitment and cellular differentiation. This study demonstrates, however, that progenitor cell responses to the same class of signals, the bone morphogenetic proteins (BMPs), change during ontogeny, and that these same signals may thus initiate progenitor cell elaboration of several different lineages. BMPs promote cell death and inhibit the proliferation of early (embryonic day 13, E13) ventricular zone progenitor cells. At later embryonic (E16) stages of cerebral cortical development, BMPs exhibit a concentration-dependent dissociation of cellular actions, with either enhancement of neuronal and astroglial elaboration (at 1-10 ng/ml) or potentiation of cell death (at 100 ng/ml). Finally, during the period of perinatal cortical gliogenesis, BMPs enhance astroglial lineage elaboration. By contrast, oligodendroglial lineage elaboration is inhibited by the BMPs at all stages. Further, application of the BMP antagonist noggin to cultured progenitors promotes the generation of oligodendrocytes, indicating that endogenous BMP signaling can actively suppress oligodendrogliogenesis. These observations suggest that developmental changes in neural progenitor cell responsiveness to the BMPs may represent a novel mechanism for orchestrating context-specific cellular events such as lineage elaboration and cellular viability.

Animals↗
PubMed1991

Regional enzyme profiles in rabbit lenses with early stages of naphthalene cataract.

The naphthalene cataract in the pigmented rabbit, in contrast to the corresponding model in the pigmented rat, is characterized by a rather unstable cataract development during the later stages. Some animals rapidly develop mature cataracts, others develop cortical cataracts with almost no further progression inspite of a continued naphthalene treatment. To get more insight into this phenomenon, a study with pigmented rabbits (8 weeks old) was designed and at different stages of cataract development lenses were separated in single layers with the Bonn freeze-sectioning device. The key enzymes of the carbohydrate metabolism and the redox potential were determined in those layers. The results of the biochemistry failed however to explain the prominent differences of cataract development in-vivo. We conclude from these findings that the naphthalene cataract model in the pigmented rabbit shall no longer be used in drug side-effect or efficacy studies.

Animals↗
PubMed1988

Early motor development and cerebral cortical morphology in rats exposed perinatally to alcohol.

Specific tests of early motor development and cerebral cortical morphology were studied in rats born from alcohol-fed mothers, pair-fed mothers, and ad libitum controls (either liquid or pellet diets). Liquid Bio-Serv diets were used. Alcohol feeding began on day 5 of pregnancy and ended on day 10 postpartum. The weight gain of the pups after birth was drastically reduced compared with pair-fed and other control groups; however, removal of the alcohol on day 10 postpartum resulted in an upswing of the growth curve that paralleled control groups. Between days 2 and 21 (postnatal) three behavioral tests of motor function were performed. Righting reflex (time for an animal to return to all four feet after being placed on its dorsum) was slightly delayed but the delay was not significant. Negative geotaxis (time for an animal to rotate 180 degrees from a head-down position on an inclined plane), and reflex suspension (time an animal maintained its grip on a crossbar) were significantly delayed (approximately 2 days) in offspring from alcohol-fed mothers. In the frontal cortex the offspring of alcohol-treated mothers, a marked decrease (approximately 25%) in thickness of Lamina VI was found while the other Lamina (I-V) were less altered. These results indicate that the effect of alcohol on the frontal cortex is related to a significant delay in motor development of reflex suspension and negative geotaxis since both of these require frontal integration.

Animals↗
PubMed2006

Pain perception development and maturation.

Newborn infants are not small adults. The pharmacokinetics and dynamics of analgesic drugs are immature at birth. Volumes of distribution, drug clearances, side-effects and drug efficacy all differ in newborns as compared to adults. Interestingly, these parameters develop before birth and during the postnatal period, reaching adult values after a period of months or years. This means that clinicians should anticipate on pharmacokinetic/pharmacodynamic (PK/PD) changes in newborns with increasing post-conceptual age. The ability to perceive pain might also be immature at birth. Lower pain thresholds due to the absence of inhibitory descending spinothalamic fibers and a not yet fully developed cortical pain memory system are points of interest for our understanding of differences in pain perception in the newborn infant. Although this is a relatively unexplored area of research in humans, we will discuss the maturation and development of neonatal pain experience and perception in this paper.

Analgesics↗
PubMed2000

c-Jun and the transcriptional control of neuronal apoptosis.

There has been considerable interest in the molecular mechanisms of apoptosis in mammalian neurons because this form of neuronal cell death is important for the normal development of the nervous system and because inappropriate neuronal apoptosis may contribute to the pathology of human neurodegenerative diseases. The aim of recent research has been to identify the key components of the cell death machinery in neurons and understand how the cell death programme is regulated by intracellular signalling pathways activated by the binding of neurotrophins or death factors to specific cell surface receptors. The aim of this commentary was to review research that has investigated the role of the Jun N-terminal kinase (JNK)/c-Jun signalling pathway in neuronal apoptosis, focusing in particular on work carried out with developing sympathetic neurons. Experiments with sympathetic neurons cultured in vitro, as well as with cerebellar granule neurons and differentiated PC12 cells, have demonstrated that JNK/c-Jun signalling can promote apoptosis following survival factor withdrawal. In addition, experiments with Jnk(-/-) knockout mice have provided evidence that Jnk3 may be required for apoptosis in the hippocampus in vivo following injection of kainic acid, an excitotoxin, and that Jnk1 and Jnk2 are required for apoptosis in the developing embryonic neural tube. However, in the embryonic forebrain, Jnk1 and Jnk2 have the opposite function and are necessary for the survival of developing cortical neurons. These results suggest that JNKs and c-Jun are important regulators of the cell death programme in the mammalian nervous system, but that their biological effects depend on the neuronal type and stage of development.

Animals↗
PubMed2006

Magnetic resonance imaging of the fetal brain and spine: an increasingly important tool in prenatal diagnosis: part 2.

Fetal MR imaging is an increasingly available technique used to evaluate the fetal brain and spine. This is made possible by recent advances in technology, such as rapid pulse sequences, parallel imaging, and advances in coil design. This provides a unique opportunity to evaluate processes that cannot be approached by any other current imaging technique, and it affords a unique opportunity for studying in vivo brain development and early diagnosis of congenital abnormalities inadequately visualized or undetectable by prenatal sonography. This 2-part review summarizes some of the latest developments in MR imaging of the fetal brain and spine and its application to prenatal diagnosis. The first part discussed the utility, safety, and technical aspects of fetal MR imaging; the appearance of normal fetal brain development; and the role of fetal MR imaging in the evaluation of fetal ventriculomegaly. In this second part, we focus on additional clinical applications of fetal MR imaging, including suspected abnormalities of the corpus callosum, malformations of cortical development, and spine abnormalities.

Brain↗