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PubMed1993

Unilateral cortical contusion injury in the rat: vascular disruption and temporal development of cortical necrosis.

Cerebrovascular disruption and cortical pathology resulting from either moderate (M-TBI) or severe (S-TBI) traumatic brain injury produced by a pneumatically-driven cortical contusion device were assessed in adult male rats sacrificed at 6 and 24 h or 8 and 30 days after injury to the right sensorimotor cortex. Epidural, subdural, subarachnoid, petechial (cortex and corpus callosum), and/or intraventricular hemorrhage was present in all animals, more extensively and severely following S-TBI. At 6 or 24 h after TBI, acidophilic (acid fuchsin-positive) neurons were numerous and widespread (S-TBI > M-TBI) in the ipsilateral contused cortex. By 8 days few acidophilic neurons were present in peri-impact regions of the ipsilateral neocortex, and none were detected in cortex 30 days postinjury. Both M-TBI and S-TBI groups had enlarged ipsilateral cortical volumes (edema) at 6 and 24 h post-contusion. Eight and 30 days after injury the mean volume of cortical necrosis was significantly larger in S-TBI than in M-TBI rats, and cortical necrosis in both TBI conditions increased between 8 to 30 days postinjury. These results indicate that this pneumatically-driven contusion device produces reliable and consistent primary and secondary cortical histopathology, the extent of which is related to the severity of initial injury.

Animals↗
PubMed2003

Occipital epilepsies: identification of specific and newly recognized syndromes.

Occipital epilepsies often elude diagnosis as they frequently masquerade as other seizure syndromes. Visual hallucinations are the key clinical symptoms indicating an occipital focus, but may be difficult to elicit on history, especially from children, and are not always present. When visual symptoms are not prominent, the seizure semiology and scalp EEG may lead the clinician away from considering an occipital focus, as they often reflect seizure propagation rather than seizure origin. Clinical and neuroimaging advances have led to the recognition of many new occipital epilepsy syndromes, which generally present in childhood or adolescence. Major groups include malformations of cortical development [focal cortical dysplasia, periventricular heterotopia (PVH), subcortical band heterotopia (SBH), polymicrogyria], vascular (including epilepsy with bilateral occipital calcifications often associated with coeliac disease), metabolic and the emerging idiopathic occipital epilepsies. The idiopathic occipital epilepsies now comprise three identifiable electroclinical syndromes of childhood and adolescence, the biological inter-relationships and overlap with idiopathic generalized epilepsies of which are discussed here. We emphasize the clues to recognition of specific occipital epilepsies, some of which now have specific treatments. Where medical therapy is ineffective, occipital corticectomy should be considered. Emerging evidence suggests that some syndromes have a good surgical outcome, and the consequences to visual function may be less severe than anticipated.

Cerebral Cortex↗
PubMed2004

Control of cortical neuron migration and layering: cell and non cell-autonomous effects of p35.

The migration, arrest, and ultimately positioning of cortical neurons require signaling activity from Reelin as well as from cyclin-dependent kinase 5 (Cdk5). Although both molecules control neuronal positioning, they achieve their effects by quite separate molecular pathways. Cdk5 is a serine-threonine kinase, the activity of which is dependent on its activating subunits p35 and p39. Mice deficient in Cdk5, p35, or both p35 and p39 display the hallmarks of disturbed cortical development, including cortical layer inversion, neuronal disorientation, and abnormal fiber infiltration. To distinguish between the cell- and non cell-autonomous functions of p35, we constructed p35+/+ <--> p35-/- chimeras using the lacZ gene as an independent marker for p35+/+ cells. In this shared developmental space, wild-type and mutant neurons behaved cell-autonomously with respect to layering. Wild-type cells formed a properly layered supercortex that is mirrored by an inverted mutant cortex lying underneath. However, this genotype-specific behavior was confined to the pyramidal population, and interneurons belonging to either genotype were indiscriminately distributed. However, there was also non cell-autonomous rescue of mutant neurons, and this rescue was specific only to early-born pyramidal neurons belonging to layer V. Rescued neurons reached the correct layer address and possessed appropriate neuronal morphology, orientation, and projections. Later-born neurons belonging to layers II and III were not rescued. These results demonstrate that p35 signaling can have both cell- and non cell-autonomous consequences, and their effects are not uniformly shared by cortical neurons born at different times or born at different places (projection neurons vs interneurons).

Animals↗
PubMed1984

Transplantation of various regions of embryonic brain tissue into the brain of adult rats.

Brain tissue from the cortex, midbrain (corpora quadrigemina ) or cerebellum was transplanted into the lateral ventricle or parenchyma of the right brain hemisphere of adult Wistar rats. Brain tissue transplants consisted of undifferentiated matrix cells and few neuroblasts. 30 and 110 days after operation transplants showed good development both in the lateral ventricle and inside parenchyma. They differentiated into organotypical and histotypical structures and cells similar to those formed in the normal development. Cortical structures developed from the cortex tissue, cerebellar structures from the cerebellum tissue, and nuclei white substance of corpora quadrigemina where formed from the midbrain tissue. Nerve and glial cells of transplants are well differentiated, tightly connected with the surrounding nervous tissue of the recipient, and remain viable by the end of the experiment. The immune response of the host to the transplant is not expressed. The behaviour of animals remains normal. The present experiments are the beginning of studies on grafting brain embryonal tissue to mammals with some nonhereditary and hereditary changes of the central nervous system (CNS) for our further investigations.

Animals↗
PubMed1975

Development of cortical somatosensory evoked potentials in rats.

The development of the contra- and ipsilateral cortical potential evoked by electrical sciatic nerve stimulation was studied in 77 male albino rats aged 5 to 45 days. A contralateral response was already recorded, as double negativity, in the youngest animals, while an ipsilateral evoked potential was not reliably present until the 10th day. At this time, however, both responses started with an inconstant positive wave and their shape was practically the same. During subsequent development the responses differed only in respect to their dominant component: in the contralateral response, the N1 wave had the highest amplitude for most of the time, while in the ipsilateral response the delayed N2 wave was the largest component. The latent periods of contralateral responses were somewhat shorter than those of ipsilateral evoked potentials. During development we noticed a phase of abrupt shortening of the latent period, which took place before the 15th day in the contralateral response and before the 20th day in the ipsilateral response. We also found a difference in the fatigability of the responses, which was greater in immature rats than in adult animals; in the ipsilateral evoked potential it approached adult values more slowly. The development of the ipsilateral response is thus delayed compared with the development of the contralateral response.

Age Factors↗
PubMed1999

The constructivist brain.

How do the representations underlying cognitive skills emerge? It is becoming increasingly apparent that answering this question requires integration of neural, cognitive and computational perspectives. Results from this integrative approach resonate with Piaget's central constructivist themes, thus converging on a 'neural constructivist' approach to development, which itself rests on two major research developments. First, accumulating neural evidence for developmental plasticity makes nativist proposals increasingly untenable. Instead, the evidence suggests that cortical development involves the progressive elaboration of neural circuits in which experience-dependent neural growth mechanisms act alongside intrinsic developmental processes to construct the representations underlying mature skills. Second, new research involving constructivist neural networks is elucidating the dynamic interaction between environmentally derived neural activity and developmental mechanisms. Recent neurodevelopmental studies further accord with Piaget's themes, supporting the view of human cortical development as a protracted period of hierarchical-representation construction. Combining constructive growth algorithms with the hierarchical construction of cortical regions suggests that cortical development involves a cascade of increasingly complex representations. Thus, protracted cortical development, while occurring at the expense of increased vulnerability and parental investment, appears to be a powerful and flexible strategy for constructing the representations underlying cognition.

Journal Article↗
PubMed1994

Cloned cells develop renal cortical collecting tubules.

We investigated the development and morphogenesis of stem cells cloned from cultured transformed collecting duct cells of the rabbit in the presence of hepatocyte growth factor/scatter factor (HGF), vitamin A, laminin and transforming growth factors, HGF and vitamin A induced peanut agglutinin (PNA) positivity in nonprincipal cells (PC) but not in PCs, only HGF induced tubule formation. Although HGF induced a tubule-like arrangement in both cell lines, tubules with PNA-positive cells were observed only in non-PC cells incubated with HGF. Vasopressin increased intracellular free calcium in PNA-negative cells but not in PNA-positive cells. Intracellular pH increased in PNA-positive cells but not in PNA-negative cells when gluconate was substituted for Cl in the buffer. Cloned non-PCs were stem cells that developed PC- and IC-like characteristics and formed collecting ducts when incubated with HGF.

Animals↗
PubMed2002

Social interest and the development of cortical face specialization: what autism teaches us about face processing.

Investigations of face processing in persons with an autism spectrum disorder (ASD) inform upon theories of the development of "normal" face processing, and the story that emerges challenges some models of the nature and origin of cortical face specialization. Individuals with an ASD possess deficits in face processing and a lack of a fusiform face area (FFA). Evidence from studies of ASD can be conceptualized best using an expertise framework of face processing rather than models that postulate a face module in the fusiform gyrus. Because persons with an ASD have reduced social interest, they may fail to develop cortical face specialization. Face specialization may develop in normal individuals because they are socially motivated to regard the face, and such motivation promotes expertise for faces. The amygdala is likely the key node in the system that marks objects as emotionally salient and could be crucial to the development of cortical face specialization.

Adolescent↗
PubMed2006

Cortical bone development under the growth plate is regulated by mechanical load transfer.

Longitudinal growth of long bones takes place at the growth plates. The growth plate produces new bone trabeculae, which are later resorbed or merged into the cortical shell. This process implies transition of trabecular metaphyseal sections into diaphyseal sections. We hypothesize that the development of cortical bone is governed by mechanical stimuli. We also hypothesize that trabecular and cortical bone share the same regulatory mechanisms for adaptation to mechanical loads. To test these hypotheses, we monitored the development of the tibial cortex in growing pigs, using micro-computer tomography and histology. We then tested the concept that regulatory mechanisms for trabecular bone adaptation can also explain cortical bone development using our mechanical stimulation theory, which could explain trabecular bone (re)modelling. The main results showed that, from the growth plate towards the diaphysis, the pores of the trabecular structure were gradually filled in with bone, which resulted in increased density and cortical bone. The computer model largely predicted this morphological development. We conclude that merging of metaphyseal trabeculae into cortex is likely to be governed by mechanical stimuli. Furthermore, cortex development of growing long bones can be explained as a form of trabecular bone adaptation, without the need for different regulatory mechanisms for cortical and trabecular bone.

Adaptation, Physiological↗
PubMed1993

Aspects of early postnatal development of cortical neurons that proceed independently of normally present extrinsic influences.

To examine the contribution of local versus extrinsic influences on postnatal development of cortical neurons, we compared the maturation of deep (infragranular) layer neurons in isolated slices of neocortex grown in organotypic culture to a similar population of neurons developing in vivo. All slice cultures were prepared from sensorimotor cortices of newborn mice (P0) and neurons in these cultures were examined at daily intervals during the first 9 days in vitro (DIV). The maturational state of neurons developing in vivo over this same time period was assessed in acute slices prepared from animals of equivalent postnatal age, P1-P9. Electrophysiological recordings were obtained from neurons in both cultured and acute slices, using Lucifer yellow filled whole-cell recording electrodes, enabling subsequent morphometric analysis of the labeled cells. We report significant changes in both cellular morphology and electrical membrane properties of these deep layer cortical neurons during the first week in culture. Morphological maturation over this time period was characterized by a two- to three-fold increase in cell body size and total process length, and an increase in dendritic complexity. In this same population of cells a three-fold decrease in input resistance and changes in the action potential waveform, including a two-fold decrease in the AP duration, also occur. The degree of morphological and electrophysiological differentiation of individual neurons was highly correlated across developmental ages, suggesting that the maturational state of a cell is reflected in both cellular morphology and intrinsic membrane properties. A remarkably similar pattern of neuronal maturation was observed in neurons in layers V, VI/SP examined in acute slices prepared from animals between P1-P9. Because our culture system preserves many aspects of the local cortical environment while eliminating normal extrinsic influences (including thalamic, brainstem, and callosal connections), our findings argue that this early phase of neuronal differentiation, including the rate and extent of dendritic growth and development of AP waveform, results from instructive and/or permissive local influences, and appears to proceed independently of the many normally present extrinsic factors.

Action Potentials↗
PubMed1998

[The value of images in diagnosis of neuron migration disorders].

OBJECTIVE: To present the fitest classification and the imaging peculiarities of the malformations of cortical development, most of which have been related with the epilepsy origin. METHODS: The study is based on an anatomical-histological classification scheme that shows three great groups of malformations of cortical development: 1. Malformations due to abnormal neuronal and glial proliferation. 2. Malformations due to abnormal neuronal migration. 3. Malformations due to abnormal cortical organization. RESULTS: The result of these abnormalities of the cortical development is the presence of several anatomical histological entities, actually perfectly identified by the magnetic resonance (MR), especially with the new high resolution methods. The most frequent entities, such as polymicrogyria, lissencephaly, pachygyria, schizencephaly, cerebral heterotopia (cortical, subcortical or subependymal), and other rarer types are reviewed according with the numerous references of the literature and the findings observed in the cases of our series of about one hundred patients which includes cases of every type of malformation. CONCLUSION: MR is a conclusive study in order to identify and classify the malformations of cortical development, most of which are associated with neurological disturbances: epilepsy, mental retardation, language and/or behavioral problems or motor dysfunction.

Brain↗
PubMed2005

BDNF-modulated spatial organization of Cajal-Retzius and GABAergic neurons in the marginal zone plays a role in the development of cortical organization.

The present study utilizes nestin-BDNF transgenic mice, which offer a model for early increased brain-derived neurotrophic factor (BDNF) signalling, to examine the role of BDNF in the development of cortical architecture. Our results demonstrate that the premature and homogeneous expression of BDNF, while preserving tangential migration from the ganglionic eminence to the cortex, impairs the final radial migration of GABAergic neurons, as well as their integration in the appropriate cortical layers. Moreover, Cajal-Retzius (CR) cells and GABAergic neurons segregate in the cortical marginal zone (MZ) in response to BDNF signalling, leading to an alternating pattern and a columnar cortical organization, within which the migration of different neuronal populations is specifically affected. These results suggest that both CR and GABAergic neurons play a role in directing the radial migration of late-generated cortical neurons, and that the spatial distribution of these cells in the MZ is critical for the development of correct cortical organization. In addition, reelin secreted by CR cells in the MZ is not sufficient to direct the migration of late-born neurons to the upper cortical layers, which most likely requires the presence of reelin-secreting interneurons in layers V-VI. We propose that in addition to modulating reelin expression, BDNF regulates the patched distribution of CR and GABAergic neurons in the MZ, and that this spatial distribution is involved in the formation of anatomical and/or functional columns and convoluted structures.

Animals↗
PubMed2006

A novel mode of tangential migration of cortical projection neurons.

Projection neurons of the developing cerebral cortex are generated in the cerebral ventricular zone and subsequently move to the developing cortical plate via radial migration. Conversely, most inhibitory interneurons originate in the ganglionic eminences and enter the developing cortical plate by tangential migration. Using immunohistochemical analysis together with tracer labeling experiments in organotypic brain slices, we show that a portion of cortical projection neurons migrates tangentially over long distances. Lineage analysis revealed that these neurons are derived from Emx1+ cortical progenitors and express the transcription factor Satb2 but do not express GABA or Olig1. In vitro and in vivo analysis of reeler mutant brains demonstrated that although reeler mutation does not influence tangential migration of interneurons, it affects the tangential migration of cortical projection neurons.

Animals↗
PubMed2002

Radial organization of developing preterm human cerebral cortex revealed by non-invasive water diffusion anisotropy MRI.

Cerebral cortical development involves a complex cascade of events which are difficult to visualize in intact, living subjects. In this study, we apply diffusion tensor imaging (DTI) to the evaluation of cortical development in human infants ranging from 26 to 41 weeks gestational age (GA). Apparent diffusion of water in cortex is maximally anisotropic at 26 weeks GA and anisotropy values approach zero by 36 weeks GA. During this period, the major eigenvector of the diffusion tensor in cerebral cortex is oriented radially across the cortical plate, in accord with a predominately radial deployment of its neuronal constituents. Values for the rotationally averaged water diffusion coefficient increase between 26 and 32 weeks GA, then decrease thereafter. These changes in DTI parameters are specific to cerebral cortex and reflect changes in underlying cortical architecture and formation of neuronal connections. Because of its correlation with tissue microstructure and non-invasive nature, DTI offers unique insight into cortical development in preterm human newborns and, potentially, detection of derangements of its basic cytoarchiteture.

Anisotropy↗
PubMed2006

Identification of small molecules that interfere with radial neuronal migration and early cortical plate development.

Using a fetal brain slice culture system that recapitulates early cortical plate (CP) development, we screened the "Diversity Set" chemical library from the National Cancer Institute in order to identify molecules that interfere with radial migration and CP formation and identified 11 candidate molecules. Although most compounds had broadly similar effects, histological and immunohistochemical studies with preplate and neuronal differentiation markers disclosed some differences in the anomalies induced, suggesting that the identified molecules may act on different targets. Selected compounds were tested for activity on signaling pathways known to be important during radial migration and CP development, namely reelin, phosphatidylinositol 3-kinase/Akt-protein kinase B(PKB)/glycogen synthase kinase-3ss (GSK3beta), atypical protein kinases C (aPKC), and Cdk5. No perturbation of reelin signaling or GSK3beta activity was detected. One molecule decreased the phosphorylation of Akt and focal adhesion kinase and may act via direct or indirect inhibition of Cdk5, whereas another inhibited phosphorylation of aPKCzeta/lambda and may interfere with cell polarity and leading edge formation or progression. These molecules potentially provide new tools to study a neuronal migration and CP development.

Animals↗
PubMed2006

An extremely rich repertoire of bursting patterns during the development of cortical cultures.

BACKGROUND: We have collected a comprehensive set of multi-unit data on dissociated cortical cultures. Previous studies of the development of the electrical activity of dissociated cultures of cortical neurons each focused on limited aspects of its dynamics, and were often based on small numbers of observed cultures. We followed 58 cultures of different densities--3000 to 50,000 neurons on areas of 30 to 75 mm2--growing on multi-electrode arrays (MEAs) during the first five weeks of their development. RESULTS: Plating density had a profound effect on development. While the aggregate spike detection rate scaled linearly with density, as expected from the number of cells in proximity to electrodes, dense cultures started to exhibit bursting behavior earlier in development than sparser cultures. Analysis of responses to electrical stimulation suggests that axonal outgrowth likewise occurred faster in dense cultures. After two weeks, the network activity was dominated by population bursts in most cultures. In contrast to previous reports, development continued with changing burst patterns throughout the observation period. Burst patterns were extremely varied, with inter-burst intervals between 1 and 300 s, different amounts of temporal clustering of bursts, and different firing rate profiles during bursts. During certain stages of development bursts were organized into tight clusters with highly conserved internal structure. CONCLUSION: Dissociated cultures of cortical cells exhibited a much richer repertoire of activity patterns than previously reported. Except for the very sparsest cultures, all cultures exhibited globally synchronized bursts, but bursting patterns changed over the course of development, and varied considerably between preparations. This emphasizes the importance of using multiple preparations--not just multiple cultures from one preparation--in any study involving neuronal cultures. These results are based on 963 half-hour-long recordings. To encourage further investigation of the rich range of behaviors exhibited by cortical cells in vitro, we are making the data available to other researchers, together with Matlab code to facilitate access.

Action Potentials↗
PubMed2004

Genetic basis of developmental malformations of the cerebral cortex.

Widespread use of noninvasive brain imaging techniques, in particular magnetic resonance imaging, has led to increased recognition of genetic disorders of cortical development in recent years. The causative genes for many of these disorders have been identified through a combination of detailed clinical and radiological analyses and molecular genetic approaches. These disease genes have been found to affect different steps of cortical development, including proliferation of neuronal progenitor cells, neuronal migration, and maintaining integrity of the pial surface. In many cases, syndromes with similar clinical phenotypes are caused by genes with related biochemical functions. In this article, we review the recent advances in molecular genetic studies of the disorders of cortical development. The identification and functional studies of the genes associated with these developmental disorders will likely lead to improvement in diagnosis and facilitate our understanding of the mechanisms of cortical development.

Animals↗
PubMedDate not supplied

Effects of in utero ethanol exposure on serotonin uptake in cortical regions.

Previously, this laboratory found that the 19- and 35- to 37-day-old offspring of rats that consumed ethanol on a chronic basis prior to parturition had a decreased cortical content of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) as well as a decreased number of cortical 5-HT1 binding sites. These results emphasized the sensitivity of the developing cortical serotonergic nerves to the effects of in utero ethanol exposure. In the present study, we examined the effects of in utero ethanol exposure on an additional component of the developing cortical serotonergic systems. Specifically, we examined the uptake of [3H]-5-HT by synaptosomes which were isolated from the motor or somatosensory regions of the cerebral cortex. The results demonstrated that the Vmax for serotonin uptake was significantly decreased (p less than 0.025) by approximately 15-20% in the motor cortices of the 19- and 35-day-old offspring of rats that consumed ethanol on a chronic basis prior to parturition. In addition, there was a significantly (p less than 0.025) approximately 30% decrease in the Km for serotonin uptake in the motor cortex of 35-day-old offspring of ethanol-fed rats. In contrast, neither the (Km) nor the Vmax for serotonin uptake were significantly altered (p greater than 0.05) in the somatosensory cortices in 19- or 35-day-old offspring of ethanol-fed rats. These results emphasize the selective sensitivity of developing cortical projections of the serotonergic system.

Aging↗