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PubMed1991

Ultrastructural organization of slice cultures from rat visual cortex.

We have been studying the fine structural organization of slice cultures prepared from the visual cortex of 6-day-old rats and cultured for 2 weeks using a roller culture technique. Neurons in culture exhibited the characteristic cytological differences between perikarya, axons and dendrites. Neuronal and glial processes formed a dense neuropil with minimal extracellular spaces, and within the neuropil there were numerous synaptic contacts. Both morphological types of cortical synapses, type I (asymmetrical) and type II (symmetrical) could be readily identified in slice cultures. The pattern of synaptic connections in culture was remarkably similar to that observed in normal cerebral cortex; asymmetrical synapses were usually found in contact with dendritic spines, less frequently with dendritic shafts, and never on perikarya, whereas symmetrical synapses were found mostly on perikarya, occasionally on dendritic shafts but never on dendritic spines. Synaptic morphology appeared mature after 2 weeks in vitro and did not show the immature features observed at the time of culture preparation. Taken together with our previous light microscopic studies, these results indicate that cortical slice cultures are organotypically organized and serve as a useful model to study mechanisms of cortical development and plasticity.

Animals↗

PubMed1979

Deficits in the visual evoked potentials of cats as a result of visual deprivation.

Visual evoked potentials in response to contrast reversal of grating patterns were used as a measure of visual function in normal and visually deprived cats. In cats which had been dark reared from birth (BD cats) there was a characteristic change in VEP waveform from normal, for both eyes and for all spatial frequencies of testing stimulus. In cats which had one eye sutured from the age of one week (MD cats), the VEP from the deprived eye was smaller for contrast reversal of coarse patterns. Kittens given only restricted periods of monocular exposure gave VEPs which resembled the pathological responses of the BD cats. However, the amplitudes of response were larger for the more experienced eye at higher spatial frequency. This work reinforces the idea that two factors govern cortical development: competition and experience. Lack of sufficient visual experience leads to severe intracortical pathology.

Aging↗

PubMed2003

Neurodevelopmental liabilities in epilepsy.

The epilepsies are a heterogenous group of cortical disorders characterized by recurrent excessive neuronal activity. In the pathophysiology of these disorders are included mechanisms of abnormal neuronal potential generation secondary to channelopathies, excitotoxic mechanisms secondary to imbalance in neuronal excitation and inhibition, and abnormalities of neuronal organization. In this article the mechanisms of the epilepsies are reviewed, in the setting of three examples: autosomal dominant nocturnal frontal lobe epilepsy, mesial temporal sclerosis and malformations of cortical development.

Cerebral Cortex↗

PubMed2003

MR imaging of fetal brain malformations.

METHODS: From the generally accepted data on the morphogenesis of the brain, the principles for the classification of brain malformations are given, and the salient features of each malformation which may be considered as independent from the developmental stage and therefore practical for MR imaging in the fetus after mid-gestation, are discussed. RESULTS AND DISCUSSION: However, the correlation with the clinical results in 150 cases of malformations out of a series of more than 1,000 cases of MR fetal brain imaging, demonstrates that beside the main, well-defined malformative entities, a significant degree of uncertainty remains. As the indication of further imaging is mainly based on the ultrasonographic findings, cases that are not identified as abnormal by US are not submitted to MRI (partial commissural agenesis and malformations of cortical development). A striking discrepancy exists between the findings of US and those of MRI, in the specific instance of the disorders of the posterior fossa (cystic malformations versus mega cisterna magna versus cerebellar defects), which may be only partly corrected by the use of strict anatomic criteria. Similar difficulties are observed for the diagnosis of nondestructive microcephaly. CONCLUSION: Long-term prospective longitudinal clinical-radiological studies of these groups of patients are needed.

Brain↗

PubMed2006

Hemimegalencephaly: clinical implications and surgical treatment.

INTRODUCTION: Hemimegalencephaly (HME) is a quite rare malformation of the cortical development arising from an abnormal proliferation of anomalous neuronal and glial cells that generally leads to the hypertrophy of the whole affected cerebral hemisphere. The pathogenesis of such a complex malformation is still unknown even though several hypotheses are reported in literature. BACKGROUND: HME can occur alone or associated with neurocutaneous disorders, such as neurofibromatosis, epidermal nevus syndrome, Ito's hypomelanosis, and Klippel-Trenonay-Weber syndrome. The clinical picture is usually dominated by a severe and drug-resistant epilepsy. Other common findings are represented by macrocrania, mean/severe mental retardation, unilateral motor deficit, and hemianopia. The EEG shows different abnormal patterns, mainly characterized by suppression burst and/or hemihypsarrhythmia. Although neuroimaging and histologic investigations often show typical findings (enlarged hemisphere, malformed ventricular system, alteration of the normal gyration), the differential diagnosis with other disorders of the neuronal and glial proliferation may be difficult to obtain. Hemispherectomy/hemispherotomy is the most effective treatment to control seizure, and it also seems to provide good results on the psychomotor development when performed early, as demonstrated by the literature review and by the reported personal series reported here (20 children). The surgical therapy of HME, however, is still burdened by a quite high complication rate and mortality risk.

Brain Diseases↗

PubMed2006

Outcome of hemispheric surgeries for refractory epilepsy in pediatric patients.

BACKGROUND: Hemispheric brain lesions are commonly associated with early onset of catastrophic epilepsies and multiple seizure types. Hemispheric surgery is indicated for patients with unilateral intractable epilepsy. Although described more than 50 years ago, several new techniques for hemispherectomy have only recently been proposed aiming to reduce operatory risks and morbidity. MATERIALS AND METHODS: We present the clinical characteristics, presurgical workup, and postoperative outcome of a series of pediatric patients who underwent hemispherectomy for medically intractable epileptic seizures. Thirty-nine patients with medically intractable epilepsy underwent surgery from 1996 to 2005. RESULTS AND DISCUSSION: We analyzed demographic data, interictal and ictal EEG findings, age at surgery, surgical technique and complications, and postsurgical seizure outcome. There were 74.4% males. Tonic and focal motor seizures occurred in 30.8 and 20.5% of the patients. Most frequent etiologies were Rasmussen encephalitis (30.8%) and malformation of cortical development (23.1%). Postsurgical outcomes were Engel classes I and II for 61.5% of the patients. In general, 89.5% of the patients exhibited at least a 90% reduction in seizure frequency. All patients had acute worsening of hemiparesis after surgery. Basically, two surgical techniques have been employed, both with similar results, although a trend has been noted toward one of the procedures which produced consistently complete disconnection. Patients with hemispheric brain lesions usually have abnormal neurological development and intractable epilepsy. When video-EEG monitoring and magnetic resonance imaging show unilateral disease, the patient may evolve with a good surgical outcome. We showed that a marked reduction in seizure frequency may be achieved, with acceptable neurological impairments.

Adolescent↗

PubMed2004

Cerebral lipoma and the underlying cortex of the temporal lobe: pathological features associated with the malformation.

Intracranial lipomas are believed to be congenital malformations rather than true neoplasms, resulting from the abnormal differentiation of the meninx primitiva, the undifferentiated mesenchyme. We report here the surgical pathological features of a lipoma that was located on the cerebral surface of an abnormally formed fissure, and the underlying cortex of the middle temporal gyrus of a 20-year-old woman. The mass was composed of typical adipose tissue in which a large number of blood vessels were present. Thick connective tissue associated with the arachnoid membrane covered the cortical surface. The cortex exhibited a polymicrogyric configuration in which the cortical ribbon was abnormally undulated and excessively folded. Reelin-immunolabeled Cajal-Retzius-cell-like cells were observed frequently in the fused molecular layer. The cortical lamination underlying the molecular layer was poorly defined. Along the border between the connective tissue and cortical surface, there was a narrow zone in which the mesenchymal and neuronal tissues were intermingled, and where immunohistochemical and ultrastructural investigations disclosed disruption of the basal lamina, prominent astrocytosis, and abundant axonal and synaptic profiles. These findings suggest that focal disturbances in cerebral cortical development occur in association with the development of lipomas.

Adult↗

PubMed2006

Neocortical neuronal arrangement in Miller Dieker syndrome.

Miller Dieker syndrome (MDS, type I lissencephaly) is a neuronal migration disorder, which is caused by deletions along the short arm of chromosome 17 (17p13.3). Recent studies would suggest that the cortical lamination in MDS is inverted, based on morphological criteria. The present neuropathological study examines the cerebral cortex from a 33-week old fetus with MDS using both neuronal and laminar-specific markers. These expression studies demonstrate a relatively preserved cortex and cortical lamination, overlying a layer of immature neurons in MDS brain. The findings are consistent with both a migratory and proliferative defect, giving rise to lissencephaly. Moreover, characterization of such rare human malformations of cortical development by immunohistochemical techniques will provide a greater understanding of the underlying mechanisms.

Aborted Fetus↗

PubMed2005

Aberrant neuronal-glial differentiation in Taylor-type focal cortical dysplasia (type IIA/B).

Focal cortical dysplasia (FCD) type IIA/B (Taylor type) is a malformation of cortical development characterized by laminar disorganization and dysplastic neurons. FCD IIA and FCD IIB denote subtypes in which balloon cells are absent or present, respectively. The etiology of FCD IIA/B is unknown, but previous studies suggest that its pathogenesis may involve aberrant, mixed neuronal-glial differentiation. To investigate whether aberrant differentiation is a consistent phenotype in FCD IIA/B, we studied a panel of neuronal and glial marker antigens in a series of 15 FCD IIB cases, and 2 FCD IIA cases. Double-labeling immunofluorescence and confocal imaging revealed that different combinations of neuronal and glial antigens were co-expressed by individual cells in all cases of FCD IIA/B, but not in control cases of epilepsy due to other causes. Co-expression of neuronal and glial markers was most common in balloon cells, but was also observed in dysplastic neurons. The relative expression of neuronal and glial antigens varied over a broad range. Microtubule-associated protein 1B, an immature neuronal marker, was more frequently co-expressed with glial antigens than were mature neuronal markers, such as neuronal nuclear antigen. Our results indicate that aberrant neuronal-glial differentiation is a consistent and robust phenotype in FCD IIA/B, and support the hypothesis that developmental defects of neuronal and glial fate specification play an important role in its pathogenesis.

Adolescent↗

PubMed2005

Robust sound classification through the representation of similarity using response fields derived from stimuli during early experience.

Models of auditory processing, particularly of speech, face many difficulties. Included in these are variability among speakers, variability in speech rate, and robustness to moderate distortions such as time compression. We constructed a system based on ensembles of feature detectors derived from fragments of an onset-sensitive sound representation. This method is based on the idea of 'spectro-temporal response fields' and uses convolution to measure the degree of similarity through time between the feature detectors and the stimulus. The output from the ensemble was used to derive segmentation cues and patterns of response, which were used to train an artificial neural network (ANN) classifier. This allowed us to estimate a lower bound for the mutual information between the class of the input and the class of the output. Our results suggest that there is significant information in the output of our system, and that this is robust with respect to the exact choice of feature set, time compression in the stimulus, and speaker variation. In addition, the robustness to time compression in the stimulus has features in common with human psychophysics. Similar experiments using feature detectors derived from fragments of non-speech sounds performed less well. This result is interesting in the light of results showing aberrant cortical development in animals exposed to impoverished auditory environments during the developmental phase.

Acoustic Stimulation↗

PubMedDate not supplied

Neonatal hemochromatosis, renal tubular dysgenesis, and hypocalvaria in a neonate.

We report a neonate with neonatal hemochromatosis (NH), renal tubular dysgenesis (RTD), and hypocalvaria. NH is a fatal condition of the newborn, characterized by severe idiopathic liver failure of intrauterine onset and siderosis, intra- and extrahepatic, with sparing of the reticuloendothelial system. RTD is characterized by short, abnormally developed cortical tubules that lack proximal tubule differentiation. Although both NH and RTD have been reported as entities with a genetic component, similar findings can be secondary to in utero insults. Hypocalvaria has been reported in association with fetal hypoxia including that secondary to angiotensin converting enzyme inhibitors. This 38-week-old infant died at 8.5 h. The small nodular liver weighed 44 g. Grossly, the kidneys were normal. Hypocalvaria was present. Microscopically, the hepatic parenchyma was distorted by fibrous tracts, proliferation of bile ducts, and abundant iron deposition in hepatocytes. Extrahepatic siderosis in the pancreas, myocardium, and other organs was consistent with NH. Proximal convoluted tubules were not seen on routine stains and markers for proximal tubules were negative. Previous reports have linked NH with RTD and RTD with hypocalvaria. This infant had all three of these rare conditions, which have been hypothesized or shown to be due to genetic factors, hypoxia, or drugs. The etiology in this case is unknown.

Abnormalities, Multiple↗

PubMed1998

Influence of long-chain polyunsaturated fatty acids on infant cognitive function.

Long-chain polyunsaturated fatty acids (LCPUFA) are important for normal visual and cortical development. In a previous study of the effects of LCPUFA on cognitive function of term infants at the age of 3 mon, we indicated that infants with evidence of reduced growth parameters at birth and impaired attention control as manifested by a late peak fixation during infant habituation assessment may benefit from LCPUFA supplementation. The aim of this prospective study was to determine whether LCPUFA supplementation and late peak fixation are related to means-end problem-solving ability in these same infants at the age of 9 mon. Term infants (58) were randomized to one of two formulas containing either LCPUFA or no LCPUFA and completed 4 mon of feeding with their formula. Cognitive function was assessed at 3 mon of age by measures of infant habituation. Infants (20 LCPUFA and 20 no-LCPUFA) completed the problem-solving assessment at 9 mon. The no-LCPUFA group had lower scores on both measures of intention and number of solutions, but neither of these differences was significant. Analysis of covariance for the effects of group and peak fixation, covaried with gestation and birth weight, showed that the number of solutions was significantly reduced in the late peak-fixation infants receiving no LCPUFA (P<0.02). Intention scores tended to be reduced in this group (P<0.06). The late peak-fixation infants who received LCPUFA had solution and intention scores similar to early peak-fixation infants receiving LCPUFA or no LCPUFA. These findings suggest that in term infants who have reduced growth parameters at birth and who show evidence of impaired attention control, information processing and problem-solving ability in infancy may be enhanced by LCPUFA supplementation.

Adult↗

PubMed2001

Infantile Spasms.

Infantile spasm is a catastrophic form of epilepsy found only in infants and young toddlers. Onset is before one year of age, with a peak incidence occurring between 4 to 7 months of age. The prevalence is difficult to calculate, but previous reviews have estimated between 1 per 2000 to 6000 live births. There are many causes of infantile spasms, including tuberous sclerosis, malformations of cortical development, hypoxic-ischemic injury, congenital infectious diseases, inborn errors of metabolism, genetic syndromes such as Aicardi's syndrome, and chromosomal abnormalities. A small percentage of patients have idiopathic infantile spasms, with no identifiable cause and premorbid normal growth and development. In order to prevent an ongoing epileptic encephalopathy with its concomitant consequences of cognitive impairment and intractable seizures, treatment should be aggressive and immediate. It is not enough to control the clinical infantile spasms. The underlying "interictal" hypsarrhythmia pattern must also be abolished if the prognosis is to be improved. Otherwise, the immature brain appears to remain hyperexcitable.

Journal Article↗

PubMed1995

Peptidergic neurons of subcortical white matter in aging and Alzheimer's brain.

Most of the neurons in the subcortical white matter of the adult cerebrum are remnants of the transient subplate cortex which appears during early cortical development. The peptidergic neurons in the subcortical white matter, beneath the striate cortex were examined qualitatively and qualitatively with immunohistochemistry for substance P, cholecystokinin, somatostatin and neuropeptide Y in seven control patients and eight patients with Alzheimer's disease. The different peptidergic subcortical neurons still persisted in normal aging. In Alzheimer's disease, however, the substance P- and somatostatin-immunoreactive neurons were decreased in numbers and showed degenerative changes.

Aged↗

PubMed1988

Age changes in electrophysiological measures of the superior colliculus and occipital cortex.

Locomotor activity and electrophysiological recordings of the superior colliculus and the occipital cortex were measured for two age groups of rats (100-105 and 230-235 days old) tested in ambient light and dark sensory conditions. Age differences in response to ambient illumination were observed in both behavioral and electrophysiological data. While no age differences were found for the superior colliculus data, cortical activity of the older rats differed from that found in the younger rats. These results are interpreted in terms of potential cortical development and arousal functions.

Aging↗

PubMed1986

Pre-stereoptic binocular vision in infants.

In a preferential looking experiment, identical patterns (vertical stripes) were presented to both eyes on one of two screens while orthogonal patterns (vertical stripes in one eye and horizontal stripes in the other) were presented on the other screen. Most infants younger than 3.5 months of age originally showed a preference for the dichoptic (interocularly orthogonal) pattern. At an average age of 3.5 months, however, they showed a sudden shift of preference from this pattern to the interocularly identical pattern. The full shift from a preference for one stimulus to the other (both statistically significant) occurred within a few weeks in most cases. The onset age of the shift in preference agreed with the onset age of fusion-rivalry discrimination found in a previous study (Birch et al., 1985). The original preference for the bincularly orthogonal patterns may be interpreted as a preference for a grid (interocularly emergent intersections) over a grating, judging from results of two control experiments. These data suggest that the pre-stereoptic system non-selectively combines information from the two eyes without regard to edge orientation because it loses eye-of-origin information at a relatively early stage of binocular visual processing. Thus, the pre-stereoptic system does not have the capability of interocular suppression. The theoretical and clinical significance of the new findings are discussed along with a neuronal model of cortical development of ocular segregation and binocular pathways.

Adult↗

PubMed1994

Two models for determining the mechanisms of damage and repair after hypoxic-ischaemic injury in the developing rat brain.

Hypoxic-ischaemic (HI) brain injury can lead to selective neuronal loss or pannecrosis. Different mechanisms of damage and recovery may be associated with either pattern of cell loss. Two preparations were developed to investigate the role of growth factors and other mechanisms associated with either of these patterns of damage in the developing brain. Twenty-one-day-old Wistar rats underwent permanent unilateral right carotid artery ligation. Following surgery, ligated rats were warmed for 2 h at 34 degrees C with 85 +/- 5% relative humidity and then exposed to either 15 or 60 min of 8% O2. The rats were killed and brains perfusion fixed 5 days post-hypoxia for histological analysis. Rats exposed to 15 min of hypoxia-ischaemia suffered no mortality and 90% developed selective neuronal loss in the frontoparietal cortex and hippocampal CA1 region of the ipsilateral hemisphere. Rats exposed to 60 min of hypoxia consistently developed cortical pannecrosis and cellular loss in the striatum, thalamus, hippocampus and dentate gyrus of the ipsilateral hemisphere. The advantage of these models were ease of preparation, consistent neuronal loss scores and low mortality. The ability to induce either selective neuronal loss or pannecrosis provides an opportunity to investigate the mechanisms of damage or recovery associated with each pattern of cell loss.

Animals↗

PubMed1985

Development and neuronal organization of dissociated and reaggregated embryonic cerebellum after intracephalic transplantation to adult rodent recipients.

Embryonic (E13) rat cerebellar primordia were dissociated and aggregated into tissue pellets by centrifugation. After transplantation into premade intracephalic cavities in adult rats, transplant development was evaluated at 2, 4 and 6 weeks survival. Within the cerebellar pellets there is an initial sorting of large neurons (Purkinje cells from deep nuclear cells) followed by the segregation of developing cortical cells into a trilaminar organization. These results suggest that this preparation should be useful for analyzing cellular interactions that determine cerebellar cytoarchitectural organization.

Animals↗