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Potassium currents in primary cultured astrocytes from the rat corpus callosum.

The corpus callosum (CC) is the main white matter tract in the brain and is involved in interhemispheric communication. Using the whole-cell voltage-clamp technique, a study was made of K(+)-currents in primary cultured astrocytes from the CC of newborn rats. These cells were positive to glial fibrillary acidic protein after culturing in Dulbecco's Modified Eagle Medium (> 95% of cells) or in serum-free neurobasal medium with G5 supplement (> 99% of cells). Astrocytes cultured in either medium displayed similar voltage-activated ion currents. In 81% of astrocytes, the current had a transient component and a sustained component, which were blocked by 4-aminopyridine and tetraethylammonium, respectively; and both had a reversal potential of -66 mV, indicating that they were carried by K(+) ions. Based on the Ba(2+)-sensitivity and activation kinetics of the K(+)-current, two groups of astrocytes were discerned. One group (55% of cells) displayed a strong Ba(2+) blockade of the K(+)-current whose activation kinetics, time course of decay, and the current-voltage relationship were modified by Ba(2+). This current was greatly blocked (52%) by Ba(2+) in a voltage-dependent way. Another group (45% of cells) presented weak Ba(2+)-blockade, which was only blocked 24% by Ba(2+). The activation kinetics and time course of decay of this current component were unaffected by Ba(2+). These results may help to understand better the roles of voltage-activated K(+)-currents in astrocytes from the rat CC in particular and glial cells in general.

4-Aminopyridine↗

Membrane currents elicited by angiotensin II in astrocytes from the rat corpus callosum.

The corpus callosum (CC) is the main white matter tract in the brain. It consists primarily of axons and glial cells. In the present work, membrane currents generated by angiotensin II (Ang II) in cultured astrocytes from the CC of newborn and 3-week-old rats were studied using the whole-cell voltage-clamp technique. After 4 days of culture, approximately 90% of cells were positive to glial fibrillary acidic protein (GFAP), indicating their astrocyte lineage. Ang II elicited inward currents in approximately 20% of cells and outward currents in approximately 4% of cells from the CC for newborn or 3-week-old rats. The main effect of Ang II on astrocytes from the newborn rat CC was a reduction of membrane conductance, by blocking of delayed rectifier K(+) currents in 96% of cells. However, no common action of Ang II was observed in cells from 3-week-old rat CC because the responses were quite variable, suggesting the participation of other ion currents. The partial agonist of AT(2) receptors, CGP-42112A, exerted effects on Ang II responses, whereas the AT(1) antagonist ZD7155 did not, suggesting that Ang II responses in CC astrocytes are predominantly mediated by activation of AT(2) receptors. This study is the first to show electrical responses generated by AT(2) receptors in glial cells from the rat central nervous system, and may help gain a better understanding of the functions of Ang II receptors in astrocytes from the rat CC in particular and of glial cells in general. (c) 2005 Wiley-Liss, Inc.

Angiotensin II↗

[Neurosurgical Embryology. Part 3: Molecular control of corpus callosum development].

The corpus callosum is the most important cerebral commissure allowing axonal fibres to cross the midline. Corpus callosum agenesis is an important condition in man that can reveal numerous genetic syndromes. The corpus callosum develops from the commissural plate, a dorsal region of the telencephalon. Then, axons growing from pyramidal neurons of cortical layer III extend and cross the midline. In experimental models, it is possible to decipher two conditions in which the development of the corpus callosum is impaired. The first condition is characterized by an impairment of the formation of the roof of the telencephalon (the primordium of the commissural plate). This condition can be explained by an abortive induction of this region by an impairment of BMP signaling. This can generate all the forms of holoprosencephaly. Other forms are due to a defective gene coding Hesx1, a transcription factor involved in the control of telencephalic morphogenesis. Such a genetic defect can be observed in human dominant forms of septo-optic dysplasia. The second condition is explained by an impairment of the molecular control of axon growth: such is the case for the couple netrin 1 and DCC or for the adhesion molecule L1.

Agenesis of Corpus Callosum↗

[Congenital malformations of the brain. 2: Malformations of the corpus callosum and holoprocencephalies].

The corpus callosum is formed between the 7th and the 20th gestational week. If this process is disrupted, partial or complete callosal agenesis may ensue. As large parts of the supra- and infratentorial brain are created during this critical period, associated anomalies need always to be searched for when callosal agenesis is present. Associations with neuro-genetic syndromes also exist. The corpus callosum is generally formed from front to back ("front-to-back rule"). Therefore, a partial callosal agenesis usually involves the posterior portion of the corpus callosum, while a secondary lesion of the corpus callosum does not follow this rule. Holoprosencephalies are a notable exception to this rule, as the frontal part of the corpus callosum is absent in spite of their classification as congenital malformations. They represent a disturbance of the differentiation and cleavage of the prosencephalon with a disruption of the separation of the cerebral hemispheres. Holoprosencephalies can be due to genetic causes, but also to intrauterine infections or other teratogenic causes. The holoprosencephalies are subdivided into alobar, semilobar and lobar holoprosencephalies. This article aims to describe the most important features of callosal agenesis and holoprosencephalies highlighting the respective imaging characteristics.

Abnormalities, Multiple↗

Isolated complete agenesis of corpus callosum.

Agenesis of corpus callosum (ACC) often accompanies other neural migration disorders and its prognosis must take these disorders and other associated abnormalities into account. Isolated complete ACC, i.e., agenesis of corpus callosum without other central nervous system anomaly, is rare. A total of six patients, aged nine months to 15 years, with isolated complete ACC diagnosed by brain image study in the past eight years of our hospital were evaluated for associated defects and prognosis. Isolated complete ACC without associated congenital heart disease (CHD) was found in four of the six patients (4/6), of whom three had normal development so far. The other two patients (2/6) were found to have associated CHD and both had poor prognosis. This result suggests that checking for any associated CHD may play an important prognostic role for isolated complete ACC patients. Therefore, it is recommendable that prenatal brain MRI and fetal echocardiography should be performed for evaluation and for genetic consultation whenever ACC is suspected.

Adolescent↗

[Ultrasonic diagnosis of agenesis of the corpus callosum].

Agenesis of the corpus callosum may be diagnosed successfully in vivo when sonograms demonstrate absence of corpus callosum, absence of pericallosal and cingulate sulci, wide interhemispheric fissure, small laterally positioned frontal horns with concave lateral borders. Two cases of corpus callosum agenesis were diagnosed in early infancy by ultrasound. Ultrasonographic anatomy of the corpus callosum and characteristic ultrasound features and neurological findings of agenesis are described.

Agenesis of Corpus Callosum↗

Diffusion tensor imaging of the corpus callosum in Autism.

The corpus callosum is the largest commissural white matter pathway that connects the hemispheres of the human brain. In this study, diffusion tensor imaging (DTI) was performed on subject groups with high-functioning autism and controls matched for age, handedness, IQ, and head size. DTI and volumetric measurements of the total corpus callosum and subregions (genu, body and splenium) were made and compared between groups. The results showed that there were significant differences in volume, fractional anisotropy, mean diffusivity, and radial diffusivity between groups. These group differences appeared to be driven by a subgroup of the autism group that had small corpus callosum volumes, high mean diffusivity, low anisotropy, and increased radial diffusivity. This subgroup had significantly lower performance IQ measures than either the other individuals with autism or the control subjects. Measurements of radial diffusivity also appeared to be correlated with processing speed measured during the performance IQ tests. The subgroup of autism subjects with high mean diffusivity and low fractional anisotropy appeared to cluster with the highest radial diffusivities and slowest processing speeds. These results suggest that the microstructure of the corpus callosum is affected in autism, which may be related to nonverbal cognitive performance.

Adolescent↗

Genitourinary malformations associated with agenesis of the corpus callosum.

Agenesis of the corpus callosum is an infrequent congenital anomaly that occurs in partial or complete forms, and is frequently associated with other craniofacial and skeletal abnormalities. An increased association with genitourinary abnormalities has not been previously defined. We reviewed the records of 22 boys and 11 girls with agenesis of the corpus callosum. Of the patients 18 had complete radiological or necroscopic evaluation and 15 had physical examinations as the sole means of evaluation. Renal anomalies were the most frequent genitourinary abnormalities identified in these children, although ureteral, genital and bladder abnormalities were also encountered. There was an exceptionally high incidence of undescended testes (23%), approximately 20-fold greater than the frequency in the normal population, possibly resulting from hypothalamic insufficiency associated with midline cranial defects. We suggest, therefore, that all patients with agenesis of the corpus callosum should be thoroughly evaluated with bladder and renal ultrasound studies to rule out any genitourinary abnormalities. Male patients with agenesis of the corpus callosum and undescended testes should undergo hypothalamic/pituitary axis testing.

Abnormalities, Multiple↗

[Corpus callosum agenesis].

BACKGROUND: Corpus callosum agenesis (CCA) is an uncommon entity, which can be diagnosed in utero. Uncertain prognosis makes prenatal counseling difficult. AIM. We have tried to establish a positive correlation between clinical history and imaging findings in patients with CCA. PATIENTS AND METHODS: We retrospectively reviewed clinical data and imaging findings of patients with callosal agenesis diagnosed at our institution between December 1995 and September 2002. RESULTS: Eight patients with CCA were found, five males and three females. Mean age at last clinical follow up was six years and six months, ranging from three months to 20 years. All diagnoses except for one were post natal. All patients underwent, at least, one magnetic resonance (MR) of the brain. Abnormal pregnancy was reported in three patients. Family history was unremarkable in all patients. Three patients were diagnosed with isolated CCA. One of these patients was asymptomatic at three months. Another had a slight language delay at seventeen months. The other patient had a mild developmental delay at five years. All other five patients had non isolated CCA and all were symptomatic, with variable clinical pictures: psicomotor developmental delay (4), epilepsy (4), hemiparesis (1), ocular apraxia (1), macrocephaly (2). CONCLUSION: Non isolated CCA is likely to have a worse prognosis. This may be of significant value in prenatal counseling.

Adolescent↗

Diffusion anisotropy in the corpus callosum.

BACKGROUND AND PURPOSE: The corpus callosum is a heterogeneous white-matter tract that connects the cerebral hemispheres. The purpose of this investigation was to study its microstructural architecture in normal human adult brains by using diffusion tensor imaging (DTI). METHODS: Two hundred consecutive patients referred for brain MR imaging underwent additional DTI with a high gradient field strength applied in six directions. Forty-two patients met the following inclusion criteria: 1) normal brain and 2) age greater than 18 years. Anisotropy maps were generated, and regions of interest were drawn around specified regions within the corpus callosum. Results were stratified by sex and age. In addition, available histologic specimens of the corpus callosum from cadaver brains were analyzed with conventional and specialized vascular staining. RESULTS: Anisotropy values in the various regions of the corpus callosum differed significantly. Average values of the anisotropy index for the genu, body, and splenium of the corpus callosum were 0.400, 0.456, and 0.539, respectively. The differences between these values are statistically significant (P <.01). Increased anisotropy was present in posterior areas in both sexes and in all three age groups examined. CONCLUSION: The results of this investigation show a statistically significant increase in anisotropy of the corpus callosum in its more posterior portions compared with its more anterior portions across sex and age groups. Although the microstructural etiology for this apparent increase in anisotropy is unclear, a number of possible mechanisms are presented.

Adult↗

The visual map in the corpus callosum of the cat.

The corpus callosum conveys all the fibers that connect areas 17 and 18 in the 2 cerebral hemispheres of the cat. The purpose of the present study was to ascertain the organization of the visual field map described by these fibers in the corpus callosum. This was achieved by injecting anterograde and retrograde pathway tracers at known locations in the callosally connected zones of areas 17 and 18. The positions of the injection sites were varied systematically to include all visual field elevations represented along the marginal and posterolateral gyri. Overall, the results show (1) that callosal fibers projecting between the 2 marginal gyri, where the lower visual fields are represented, pass through the body of the corpus callosum; (2) that fibers connecting the junction of the marginal and posterolateral gyri in the 2 hemispheres, where central fields are represented, pass through the dorsal splenium of the corpus callosum; and (3) that fibers passing between the ventral portions of the 2 posterolateral gyri, where upper fields are represented, pass through posterior and ventral splenium. In addition, the density of visual fibers in the splenium is greater than in the body of the corpus callosum. Within the overall pattern, a finer arrangement exists, and it was possible, by comparison with the cortical visual field maps, to describe a map of visual field elevations in the corpus callosum. In this map, the representations of the different visual field elevations are not a simple reflection of the map in the cortex. The map of the lower fields contained in the body is spread out, whereas the map of the central and upper fields in the splenium is highly compressed. The high degree with which observations can be reproduced in different cats indicates that the map is stereotyped from one animal to another.

Animals↗

Functional tests of the corpus callosum in schizophrenia.

The corpus callosum, a cerebral commissure of 200,000,000 fibres, is thickened in chronic schizophrenia and several neuropsychological and neurophysiological techniques have suggested poor links between the two cerebral hemispheres. The interhemispheric conduction time across the corpus callosum, measured in 12 schizophrenics, using the ipsilateral/contralateral latency differences of the early somatosensory evoked response, was found to be effectively zero. It is suggested that schizophrenia is a split-brain condition akin to agenesis of the corpus callosum, unrecognized through the use of compensatory ipsilateral sensory pathways.

Adolescent↗

One hundred million years of interhemispheric communication: the history of the corpus callosum.

Analysis of regional corpus callosum fiber composition reveals that callosal regions connecting primary and secondary sensory areas tend to have higher proportions of coarse-diameter, highly myelinated fibers than callosal regions connecting so-called higher-order areas. This suggests that in primary/secondary sensory areas there are strong timing constraints for interhemispheric communication, which may be related to the process of midline fusion of the two sensory hemifields across the hemispheres. We postulate that the evolutionary origin of the corpus callosum in placental mammals is related to the mechanism of midline fusion in the sensory cortices, which only in mammals receive a topographically organized representation of the sensory surfaces. The early corpus callosum may have also served as a substrate for growth of fibers connecting higher-order areas, which possibly participated in the propagation of neuronal ensembles of synchronized activity between the hemispheres. However, as brains became much larger, the increasingly longer interhemispheric distance may have worked as a constraint for efficient callosal transmission. Callosal fiber composition tends to be quite uniform across species with different brain sizes, suggesting that the delay in callosal transmission is longer in bigger brains. There is only a small subset of large-diameter callosal fibers whose size increases with increasing interhemispheric distance. These limitations in interhemispheric connectivity may have favored the development of brain lateralization in some species like humans.

Animals↗

Regional pattern of increased water diffusivity in hippocampus and corpus callosum in mild cognitive impairment.

BACKGROUND: Corpus callosum atrophy possibly indicates neuronal degeneration in association cortex in Alzheimer's disease (AD). Water diffusivity allows detecting physiological changes that probably occur earlier than structural shrinkage in cerebral regions during the development of AD. OBJECTIVE: To simultaneously investigate the focal volumetric and early structural changes with apparent diffusion coefficient (ADC) of corpus callosum in mild cognitive impairment (MCI), and to explore the regional pattern of ADC increase in hippocampus and corpus callosum. METHODS: Thirteen subjects with MCI and 13 healthy age-matched control subjects were studied. With three-dimensional volumetric spoiled gradient recalled echo MRI images, we measured the volume of hippocampus and corpus callosum. Using MRI-guided diffusion-weighted imaging analysis, we calculated ADCs from hippocampus and corpus callosum. Within the receiver-operation curve (ROC) statistical framework, areas under ROC curves from hippocampal and callosal ADCs were compared in differentiating between MCI and controls. RESULTS: After normalization to intracranial volume, hippocampal, not callosal, volume was significantly reduced in MCI. ADC values were increased in hippocampus and corpus callosum in MCI. The extent of ADC increase was similar between hippocampus and corpus callosum. CONCLUSION: Alterations in water diffusivity may precede corpus callosum atrophy during the development of MCI. Diffusion changes might occur simultaneously in allocortex and neocortex in MCI.

Aged↗

Axons of early generated neurons in cingulate cortex pioneer the corpus callosum.

The internal capsule and corpus callosum are the two major efferent axonal pathways of the mammalian neocortex. Previous studies have shown that the first cortical axons to grow through the internal capsule, the pathway from cortex to its subcortical targets, are extended by subplate neurons, which are the earliest generated neurons in the neocortex. Here, we characterize the origin of the first axons to project through the other major efferent pathway of the cortex, the midline corpus callosum, which connects the two cortical hemispheres. Using anterograde Dil tracing, we show that cortical axons first cross the midline through the nascent corpus callosum at E17. Retrograde Dil labeling from medial cortex at E18 reveals that these axons originate from a discrete group of neurons in medial (presumptive cingulate) cortex. These early callosal cells have complex morphologies with highly branched dendrites and later appear to take on a pyramidal form characteristic of callosal neurons in deep layers of cingulate cortex. 3H-thymidine birthdating demonstrates that these cells are predominantly generated on E14, making them among the earliest generated neurons in this cortical region. Injections of retrograde tracers in one cortical hemisphere at late embryonic or early postnatal ages result in substantial numbers of neurons labeled in the ipsilateral subplate, but only a few neurons labeled in the contralateral subplate. Thus, subplate neurons do not pioneer or ever project in significant numbers through the corpus callosum. We conclude that the two major efferent pathways from cortex, the corpus callosum and the internal capsule, are pioneered by developmentally and spatially distinct populations of early generated cortical neurons.

Aging↗