Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “cortical development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources
PubMed2004

Clinical features and long term outcome of epilepsy in periventricular nodular heterotopia. Simple compared with plus forms.

OBJECTIVES: Little is known about the long term outcome of patients with periventricular nodular heterotopia (PNH) and epilepsy, particularly the course of seizures. This study investigated the electroclinical and prognostic features of 16 patients with PNH. METHODS: Of 120 patients with epilepsy and malformations of cortical development, 16 had PNH. Of these, eight patients had periventricular nodules only (simple PNH) and eight also presented with other cortical or cerebral malformations (subcortical heterotopia; polymicrogyria; focal dysplasia; schizencephaly; cortical infolding; agenesis of the corpus callosum; mega cisterna magna and cerebellar atrophy) (PNH plus). All patients underwent clinical, neurophysiological, and MRI investigation. The mean follow up was 17.3 years (2-40 years). RESULTS: Two electroclinical patterns emerged: (1) The first pattern, associated with simple PNH, was characterised by normal intelligence and seizures, usually partial, which began during the second decade of life. The seizures never became frequent and tended to disappear or become very rare. The EEG showed focal abnormalities. (2) The second pattern, associated with PNH plus, was characterised by mental retardation and seizures that began during the first decade of life. The seizures were very frequent in most cases and sudden drops were observed in six patients. Seizures were medically refractory in four patients. The EEG showed focal and bisynchronous abnormalities. CONCLUSIONS: Two groups of PNH patients with different electroclinical and neuroradiological features can be identified after a long term follow up. The presence of other types of cortical or cerebral malformations, in addition to periventricular nodules, determines a poor prognosis.

Abnormalities, Multiple↗
PubMed1998

Cyclin-dependent kinase 5-deficient mice demonstrate novel developmental arrest in cerebral cortex.

The cerebral cortex of mice with a targeted disruption in the gene for cyclin-dependent kinase 5 (cdk5) is abnormal in its structure. Bromodeoxyuridine labeling reveals that the normal inside-out neurogenic gradient is inverted in the mutants; earlier born neurons are most often found superficial to those born later. Despite this, the early preplate layer separates correctly and neurons with a normal, pyramidal morphology can be found between true marginal zone and subplate. Consistent with their identity as layer VI corticothalamic neurons, they can be labeled by DiI injections into thalamus. The DiI injections also reveal that the trajectories of the cdk5(-/-) thalamocortical axons are oblique and cut across the entire cortical plate, instead of being oriented tangentially in the subcortical white matter. We propose a model in which the cdk5(-/-) defect blocks cortical development at a heretofore undescribed intermediate stage, after the splitting of the preplate, but before the migration of the full complement of cortical neurons.

Animals↗
PubMed1996

Differential distribution of AMPA receptors and glutamate during pre- and postnatal development in the visual cortex of ferrets.

Immunohistochemical methods were used to study the distribution and time-course of appearance of cells expressing glutamate and alpha-amino-3-hydroxy-5-methyl-4-isoaxazole propionic acid (AMPA)-type glutamate receptors (GluR1 and GluR2/3) during development of the ferret visual cortex. Glutamate is present in many neurons in the ventricular zone, intermediate zone, developing cortical plate, and marginal zone as early as embryonic day (E) 34 (birth is at E41 in ferrets). Glutamate attains its adult distribution coincident with the completion of cellular migration. By contrast, GluR1 immunoreactivity emerges more slowly. By birth, GluR1 immunoreactivity is present only in a few neurons in the marginal zone and ventricular zone but is abundant in the marginal zone and subplate, where synaptogenesis commences. The number and staining intensity of GluR1-positive cells increases dramatically during the first two postnatal weeks and is maximal between the second and third week, before slowly declining to adult levels. Cortical cells immunopositive for GluR2/3 follow a similar pattern, although their distribution differs: GluR2/3-positive cells are mainly pyramidal cells. During the first postnatal week, GluR2/3 is also transiently present in fibers in the intermediate zone, which at this stage contains many thalamocortical and callosal and corticofugal axons. The abundance of glutamate at fetal stages, especially in the ventricular zone, is consistent with the previously proposed role of glutamate in mediating trophic effects in vivo, as previously demonstrated in vitro. The expression of AMPA receptors, as well as their transient overexpression, confirms the results of in situ hybridization studies and may imply a developmental role in neuronal differentiation for these receptors, in addition to their mature role in mediating cortical transmission.

Animals↗
PubMed2001

Development of the perforating pathway: an ipsilaterally projecting pathway between the medial septum/diagonal band of Broca and the cingulate cortex that intersects the corpus callosum.

The perforating pathway (PFP) intersects the corpus callosum perpendicularly at the midline in the dorsoventral axis. Therefore axons in either the PFP or the corpus callosum make different axonal guidance decisions in the same anatomical region of the developing cortical midline. The mechanisms underlying these axonal choices are not known. To begin to identify these guidance mechanisms, we characterized the development of these two pathways in detail. The development of the corpus callosum and its pioneering projections has been described elsewhere (Shu and Richards [2001] J. Neurosci. 21:2749--2758; Rash and Richards [2001] J. Comp. Neurol. 434:147--157). Here we examine the development, origins, and projections of axons that make up the PFP. The majority of axons within the PFP originate from neurons in the medial septum and diagonal band of Broca complex. These neurons project in a topographic manner to the cingulate cortex. In contrast to previous reports, we find that a much smaller projection originating from the cingulate cortex also contributes to this pathway. The pioneering projections of the PFP and the corpus callosum arrive at the corticoseptal boundary at around the same developmental stage. These findings show that ipsilaterally projecting PFP axons and contralaterally projecting callosal axons make distinct guidance decisions at the same developmental stage when they reach the corticoseptal boundary.

Animals↗
PubMed1993

Chick gonadogenesis following early surgical bursectomy. I. Histological, morphometric and histochemical data on the embryonic left ovary.

Left ovaries of bursectomized chick embryos were examined on the 17th day of incubation in comparison to normal and sham-operated controls, by histological and histochemical observations. The results show that in bursectomized embryos the cortex appears irregularly developed, with a significant decrease in the mean thickness and in the percentage of the secondary sex cords in the total cortical area. Furthermore, the germinal epithelium appears thicker and the subcortical medulla and the tunica albuginea more compact. The greater activity of the enzyme delta 5-3 beta-hydroxysteroid dehydrogenase (delta (5)3 beta HSD) found in ovaries of bursectomized embryos (histochemical method) could be related to an endocrine dismetabolism affecting the cortical development. On the basis of these results and those of other authors, some hypotheses are advanced. In particular, an action of the bursal factor on GTH receptors could be the factor responsible of the enhanced steroidogenic activity altering the hormonal environment.

Animals↗
PubMed1999

Clinical spectrum of cortical dysplasia in childhood: diagnosis and treatment issues.

Disorders of cortical development form a spectrum of lesions produced by insults to the developing neocortex. These conditions typically first manifest in childhood with epilepsy, developmental delay, and focal neurologic signs. Although the clinical and electrophysiologic findings are often nonspecific, high-resolution magnetic resonance imaging facilitates diagnosis during life, and assists in delineating specific clinical syndromes. While many patients are dysmorphic and severely affected by mental retardation and epilepsy, some have normal or near-normal cognitive function and no seizures. Molecular studies of dysplastic cortex are providing new insights into the basic mechanisms of brain function and development, while pathologic analysis of tissue removed at surgery is helping to define epileptic circuitry. Treatment of the epilepsy associated with cortical dysplasia is often frustrating, but surgical approaches based on accurately defining epileptogenic regions are proving increasingly successful. Genetic diagnosis is important for accurate counseling of families.

Brain Diseases↗
PubMed1997

Determination of the migratory capacity of embryonic cortical cells lacking the transcription factor Pax-6.

The cerebral cortex forms by the orderly migration and subsequent differentiation of neuronal precursors generated in the proliferative ventricular zone. We studied the role of the transcription factor Pax-6, which is expressed in the ventricular zone, in cortical development. Embryos homozygous for a mutation of Pax-6 (Small eye; Sey) had abnormalities suggesting defective migration of late-born cortical precursors. When late-born Sey/Sey precursors were transplanted into wild-type embryonic rat cortex, they showed similar integrative, migrational and differentiative abilities to those of transplanted wild-type mouse precursors. These results suggest that postmitotic cortical cells do not need Pax-6 to acquire the capacity to migrate and differentiate, but that Pax-6 generates a cortical environment that permits later-born precursors to express their full developmental potential.

Animals↗
PubMed1999

Epilepsy and malformations of the cerebral cortex.

Abnormal cortical development is increasingly recognized as a cause of human epilepsy. Development of the cerebral cortex involves three distinct but overlapping processes consisting of neuronal and later glial proliferation, neuronal migration and cortical organization. Cortical malformations can originate from abnormalities of any or all of these processes. Certain malformations are known to be genetically determined, while for others a genetic origin has been hypothesized. In addition, there are some that may be linked to prenatal insult. Some malformations are notably more epileptogenic than others. In specific forms, epileptogenesis appears to originate from intrinsic properties of the dysplastic tissue, and is stereotyped in expression. Cortical malformations are also known that are affected by age-related influence and may be accompanied by different epileptic syndromes, sometimes with good long-term outcome. In patients with intractable seizures which are symptomatic of a cortical malformations it is necessary to diagnose the type of malformation and the associated epileptic syndromes and to assess the characteristics of epileptogenesis. Planning of surgical treatment of the associated epilepsy must rely on careful evaluation of all these informations.

Cerebral Cortex↗
PubMed2002

Life-saving epilepsy surgery for status epilepticus caused by cortical dysplasia.

A uniquely successful neurosurgical intervention in a four-month-old child suffering from status epilepticus (SE) caused by focal cortical dysplasia is reported. Seizures appeared at postnatal day 10 and culminated as medically intractable focal motor SE three months later. The first MRI scan at postnatal week 2 was inconclusive; electroclinical features typical of malformations of cortical development led to the repetition of MRI at the age of 3 months that confirmed the correct diagnosis. Since all medical trials including thiopental anaesthesia have been unsuccessful in treatment of SE, urgent resection of the right frontal and parietal lobes was performed at 4 months of age. One month later, the child had become seizure-free and her psychomotor development is proceeding well. Histopathological analysis of the resected brain tissue revealed abnormalities typical of the Taylor's type of focal cortical dysplasia. The aim of the report is to encourage considering surgery in selected patients suffering from medically intractable SE early in life.

Cerebral Cortex↗
PubMed2000

Postlesional epilepsy: the ultimate brain plasticity.

Lesions that occur either during fetal development or after postnatal brain trauma often result in seizures that are difficult to treat. We used two animal models to examine epileptogenic mechanisms associated with lesions that occur either during cortical development or in young adults. Results from these experiments suggest that there are three general ways that injury may induce hyperexcitability. Direct injury to cortical pyramidal neurons causes changes in membrane ion channels that make these cells more responsive to excitatory inputs, including increases in input resistance and a reduction in calcium-activated potassium conductances that regulate the rate of action potential discharge. The connectivity of cortical circuits is also altered after injury, as shown by axonal sprouting within pyramidal cell intracortical arbors. Enhanced excitatory connections may increase recurrent excitatory loops within the epileptogenic zone. Hyperinnervation attributable to reorganization of thalamocortical, callosal, and intracortical circuitry, and failure to prune immature connections, may be prominent when lesions affect the developing neocortex. Finally, focal injury can produce widespread changes in gamma-aminobutyric acid and glutamate receptors, particularly in the developing brain. All of these factors may contribute to epileptogenesis.

Action Potentials↗
PubMedDate not supplied

Development of cat somatosensory cortex: structural and metabolic considerations.

Although research is beginning to clarify the relationship between structure and functional activity in the adult cerebral cortex, little is known about cortical development in the somatosensory cortex of cats. A number of parameters were used in this study to identify functional and anatomical correlates in the developing somatosensory cortex of kittens ranging in age from 3 to 33 d: 2-deoxyglucose (2DG) uptake, cytochrome oxidase (CO) activity, Nissl staining, and AChE activity. All of these parameters were found to reflect an immaturity that evolved to the adult-like pattern by 4-5 weeks of age. Nissl staining revealed an immature laminar pattern at birth, in which layers I, V, and VI were distinct whereas layers II-IV were homogeneous in appearance. Numerous cells could be observed at the layer VI-white matter junction and throughout the white matter, a feature not found in adults. The laminar distribution of Nissl-stained cells gradually became mature by 4-5 weeks of age. CO staining was homogeneous throughout all layers, in contrast to the adult pattern, which displays laminar differentiation. In young animals, many darkly stained CO+ cells were found at the layer VI-white matter border and in the white matter, a distribution not found in the adult. AChE staining in kittens was also distinctly different from that in adults. At birth, AChE+ fibers could be found in layers I, V, and VI but were scarce in layers II-IV. In the adult, a dense network of AChE+ fibers can be found in all layers. 2DG uptake was also immature, as little stimulus-evoked activity could be observed in animals younger than 2 weeks. A dense band of metabolic activity was found in the zone between layer VI and the white matter, whether or not a somatic stimulus was delivered. These results suggest a close correlation between the developing cytoarchitecture and the emergence of a mature pattern of functional activity in the somatosensory cortex.

Acetylcholinesterase↗
PubMed2001

Human neocortical development: the importance of embryonic and early fetal events.

The identification of numerous genes involved in the development of the cerebral cortex has led to an increased interest in the early stages of corticogenesis, when the first postmitotic neurons migrate into the cortical plate to form the foundation of the adult cortex. However, the cellular substrate of gene expression in early human cortical development is widely unknown. This article analyzes the complex sequence of events in the differentiation of the preplate, the predecessor of the neocortex, and discusses the possible origin and migratory routes of the neuronal populations involved in the transition from preplate to cortical plate. The neuronal classes present in embryonic and early fetal stages are redefined in terms of their relationship with the Reelin-Dab1 signaling pathway whose integrity is essential for successful migration into the cortex. A timetable of developmental steps is provided, and the peculiarities of the preplate derivatives in the human brain, marginal zone, and subplate are discussed. The results presented here may contribute to a deeper understanding of the pathogenesis of migration disorders.

Animals↗
PubMed1990

Perinatal radiation-induced renal damage in the beagle.

The developing perinatal kidney is particularly sensitive to radiation. The pathogenesis of the radiation-induced lesion is related to the destruction of outer cortical developing nephrons and direct radiation injury with secondary hemodynamic alterations in remnant nephrons. In this study, which is part of a life span investigation of the effects of whole-body gamma radiation during prenatal and early postnatal life, dogs were given 0, 0.16, 0.83, or 1.25 Gy irradiation at either 55 days postcoitus or 2 days postpartum and were examined morphometrically and histopathologically at 70 days of age. Although irradiated dogs showed no reduction in the total number of nephrons per kidney, there was a significant increase in the total number and relative percentage of immature, dysplastic glomeruli. In addition, deeper cortical glomeruli of irradiated kidneys exhibited mesangial sclerosis similar to that associated with progressive renal failure in our previous studies. These findings are in accord with those reported at doses of 2.24 to 3.57 Gy and demonstrate that the perinatal kidney is affected by radiation doses much lower than previously demonstrated.

Animals↗
PubMed1998

Changes in the F-actin cytoskeleton during neurosensory bristle development in Drosophila: the role of singed and forked proteins.

Drosophila neurosensory bristle development provides an excellent model system to study the role of the actin-based cytoskeleton in polarized cell growth. We used confocal fluorescence microscopy of isolated thoracic tissue to characterize changes in F-actin that occurred during macrochaete development in wild type flies and mutants that have aberrant bristle morphology. At the earliest stages in wild type bristle development, cortical patches of F-actin were present, but no bundles were observed. Actin bundles began to form at 31% of pupal development and became more prominent as development progressed. The F-actin patches gradually disappeared and were no longer present by 38% of pupal development. The distribution of F-actin in singed3 mutant macrochaetae was indistinguishable from wild type bristles until 35% of development when the actin bundles began to splay and appear ribbon-like. In forked36a bristles, the mutant phenotype was evident at earlier stages of development than the singed3 mutant. Wild type tissue stained with antibodies against the forked protein demonstrated that the forked protein colocalized with F-actin structures found in early and late stage developing macrochaetae. Antibodies against the singed protein showed it appeared to localize with F-actin structures only at later stages in development. These data suggested that the forked gene product was required for the initiation of fiber bundle formation and the singed gene product was required for the maintenance of fiber bundle morphology during bristle development. Similar analyses of singed3/forked36a double mutants provided additional genetic evidence that the forked gene product was required before the singed gene product. Further, the analyses suggested that at least one additional crosslinking protein was present in these bundles.

Actins↗
PubMed2003

Cortical dysplasia in extratemporal lobe intractable epilepsy: a study of 52 cases.

Cortical dysplasias or malformations due to abnormalities of cortical development are a well-recognized cause of intractable seizures. This study retrospectively examines the clinicopathologic features of 52 cases of extratemporal cortical dysplasia (from 135 total resections performed over a 16-year period). The study consists of 52 patients (27 males; 25 females) who underwent extratemporal resection for epilepsy at a mean age of 15.1 years (range, 3 months to 44.1 years). Seizure duration before surgery ranged from 7 to 372 months (mean duration, 129 months). Patterns of cortical dysplasia observed included diffuse architectural disorganization (n=48), neuronal cytomegaly (n=32), increased number of molecular layer neurons (n=32), balloon cells (n=19), gray matter heterotopia (n=3), neuronal glial clustering (n=3), and pial glial neuronal tissue (n=2). Five patients had coexistent nodular hamartomas. Coexistent tumors were present in five patients; including three dysembryoplastic neuroepithelial tumors, one ganglioglioma, and one low-grade fibrillary astrocytoma. Two patients had tuberous sclerosis. Follow-up was available in 50 patients (mean follow-up, 29 months). Thirty-eight patients (73%) had complete resolution or significant decrease in seizure frequency, 13 patients (25%) had increased seizures or no change in seizures, and one patient died in the postoperative period. In conclusion, (1). cortical dysplasia was identified in 38.5% of extratemporal resections for epilepsy; (2). the common cortical dysplasia patterns observed included diffuse cortical disorganization, neuronal cytomegaly, and increased molecular layer neurons; (3). 10% of extratemporal cortical dysplasia was associated with tumors; (4). improved seizure control was obtained in approximately three fourths of patients after resection; and (5). seizures associated with balloon cell dysplasia were less successfully managed with surgery.

Adolescent↗
PubMedDate not supplied

[Advances in our knowledge of the causation and pathophysiology of reflex epilepsies].

AIMS: In recent years our knowledge of the pathophysiology and aetiology of reflex seizures and epilepsies has advanced significantly due to the contributions made by modern functional neuroimaging and neurophysiology techniques, as well as the findings of research being conducted in molecular biology. The aim of our review is to summarise and integrate these contributions in order to describe the current state of our knowledge on the subject. DEVELOPMENT: The fundamental pathophysiological pattern is common to all types of reflex epilepsy and is based on the existence of a hyperexcitable cortical or subcortical neuronal area that can respond to a physiological stimulus in an exaggerated manner. This focal hyperexcitability may derive from a predisposing genetic substrate (idiopathic reflex epilepsy) or from a focal cortical lesion (lesional reflex epilepsy). Some genetic substrates have been reported in isolated families and there are many candidate genes, but we still do not know enough about the genetic base. The lesion-based aetiology is very heterogeneous, but disorders affecting cortical development are the lesions with the greatest capacity to cause reflex epilepsy. Clinical expression is conditioned by the topography of the lesion and not by the type of underlying lesion. CONCLUSIONS: Future characterisation of reflex epileptic seizures and syndromes must include a diagnosis centred around three axes, that is, topographic, lesional and genetic.

Animals↗
PubMed1999

Regulation of stretch-activated intracellular calcium transients by actin filaments.

Stretch activation of cation-permeable channels may be an important proximal sensory mechanism in mechanotransduction. As actin filaments may mediate cellular responses to changes of the mechanical properties of the substrate and regulate stretch-induced calcium transients, we examined the role of actin filaments and substrate flexibility in modulating the amplitude of stretch-activated intracellular calcium transients. Human gingival fibroblasts were subjected to mechanical stretch through integrins by magnetic force acting on collagen-coated ferric oxide beads. Intracellular calcium concentration was measured in fura-2-loaded cells by ratio fluorimetry. Cytochalasin D-treatment greatly increased (3-fold) the amplitude of stretch-activated calcium transients in well-spread cells grown on glass coverslips while phalloidin, colchicine or taxol exerted no signficant effects, indicating that actin filaments but not microtubules modulate stretch-activated calcium transients. In freshly plated cells with rounded shapes and poorly developed cortical actin filaments, stretch-induced calcium transients were of 3-fold higher amplitude than well-spread cells plated for 6-24 hrs and with well developed actin filaments. Cells plated on soft collagen-polyacrylamide gels showed round morphology but exhibited <50% of the response to stretch of well-spread cells on inflexible gels. Notably, cells on soft gels showed very heavy phalloidin staining for cortical actin filaments compared with cells on more inflexible surfaces which showed only light staining for cortical actin. While cell shape may have some effect on responsiveness to mechanical stretch, the rigidity of the cell membrane mediated by the extensive cortical actin network appears to be a central determinant in the regulation of stretch-induced calcium signals.

Actin Cytoskeleton↗
PubMed1996

Regulation of alpha7 nicotinic acetylcholine receptors in the developing rat somatosensory cortex by thalamocortical afferents.

Distributions of alpha7 nicotinic acetylcholine receptor (nAChR) mRNA and [125]alpha-bungarotoxin (alpha-BTX) binding sites in the developing rat somatosensory cortex were characterized in relation to acetylcholinesterase (AChE) histochemical staining of thalamocortical terminals to investigate the role of this receptor in cortical development. Using quantitative in situ hybridization and receptor autoradiography, elevated levels of mRNA and binding-site expression were first detected at post-natal day 1 (P1) in deep and superficial layers, just beneath the AChE-stained thalamocortical terminals. Onset of expression occurred approximately 1 d after ingrowth of AChE-stained thalamocortical afferents. By P5, mRNA and binding-site expression exhibited a disjunctive, barrel-like pattern in layer IV and, more clearly, in layer VI. The mRNA and binding-site expressions peaked at approximately 1 week postnatal and then declined to adult levels. Unilateral electrolytic or cytochemical lesions placed in the thalamic ventrobasal complex at P0 (just as thalamocortical afferents are innervating the cortex) and at P6 (when the somatotopic map is well established) resulted in a marked reduction of alpha7 nAChR mRNA and [125]alpha-BTX binding-site levels in layers IV and VI, indicating their regulation by thalamocortical afferents. With P6 lesions, this reduction was observed as early as 6 hr postlesion. These results suggest that alpha7 nAChRs are localized primarily on cortical cells in rat somatosensory cortex and provide further evidence for thalamocortical influence on cortical ontogeny. These data also suggest a role for cholinergic systems during a critical period of cortical synaptogenesis.

Aging↗