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Studies of the ultrastructure and permeability of the blood-brain barrier in the developing corpus callosum in postnatal rat brain using electron dense tracers.

The ultrastructure of the capillaries and their permeability to lanthanum ions and ferritin in the corpus callosum was examined in postnatal rat brain. In 1 and 7-d-old rats, numerous pinocytotic vesicles were observed in the endothelial cytoplasm of the callosal capillaries. Tight junctions were present between adjacent endothelial cells which were surrounded by an ill defined layer of basal lamina. The latter was almost devoid of astrocytic association in 1 d rats and partially covered by astrocytic end-feet in 7 d rats. Pericytes were a common feature. Amoeboid microglial cells were in direct contact with some parts of the vascular wall. Large extracellular spaces were present around the capillaries. In 14 d rats, the walls of the callosal capillaries became more well developed and were surrounded by a continuous sheath of astrocytic end-feet. The basal lamina became denser and well defined. The pericapillary spaces had diminished. Immunostaining for GFAP confirmed that, with age, the walls of the callosal capillaries became increasingly covered by the astrocytic end-feet. After perfusion with lanthanum, the tracer was deposited on the luminal surface but not in the abluminal side of the endothelial cells; the passage of the tracer was apparently obstructed in the intercellular space by the tight junctions in both the 1 and 14 d rats. When injected intravenously in 1-7 d rats, ferritin was transported across the endothelial cells by transcytosis and consequently taken up by the pericytes and amoeboid microglial cells contacting the basal lamina. In 14 d rats, the injected ferritin was only found in the endothelial cytoplasm. It was concluded that the difference in the capillary permeability to exogenous material in 1-7 and 14 d rats is due to the difference in the activities of the transendothelial transport. The pericytes and amoeboid microglial cells associated with the capillary probably play a role as phagocytes in maintaining the function of the blood-brain barrier by trapping any serum-derived foreign substances with astrocytes having a regulatory role in the formation of the barrier.

Animals↗

Wax therapy for dry feet in leprosy.

A comparative study of the effect of wax therapy and foot soaks on dry plantar skin was conducted in patients with leprosy. Thirty patients with varying grades of fissures and callosities were given wax therapy for feet, and 20 similar patients were given foot soaks. Patients given wax therapy felt subjectively much better than those who had soaking. Healing of cracks and fissures and softening of callosities was observed more frequently in patients with wax therapy. These differences are statistically significant. As an institutional method wax therapy has definite advantages for treating patients with fissures and callosities, whereas soaking of the feet is easy and readily available in patients' homes to restore the dry skin to normal.

Foot Diseases↗

Functional specificity of long-range intrinsic and interhemispheric connections in the visual cortex of strabismic cats.

The development of both long-range intracortical and interhemispheric connections depends on visual experience. Previous experiments showed that in strabismic but not in normal cats, clustered horizontal axon projections preferentially connect cell groups activated by the same eye. This indicates that there is selective stabilization of fibers between neurons exhibiting correlated activity. Extending these experiments, we investigated in strabismic cats: (1) whether tangential connections remain confined to columns of similar orientation preference within the subsystems of left and right eye domains; and (2) whether callosal connections also extend predominantly between neurons activated by the same eye and preferring similar orientations. To this end, we analyzed in strabismic cats the topographic relationships between orientation preference domains and both intrinsic and callosal connections of area 17. Red and green latex microspheres were injected into monocular iso-orientation domains identified by optical imaging of intrinsic signals. Additionally, domains sharing the ocular dominance and orientation preference of the neurons at the injection sites were visualized by 2-deoxyglucose (2-DG) autoradiography. Quantitative analysis revealed that 56% of the retrogradely labeled cells within the injected area 17 and 60% of the transcallosally labeled neurons were located in the 2-DG-labeled iso-orientation domains. This indicates: (1) that strabismus does not interfere with the tendency of long-range horizontal fibers to link predominantly neurons of similar orientation preference; and (2) that the selection mechanisms for the stabilization of callosal connections are similar to those that are responsible for the specification of the tangential intrinsic connections.

Animals↗

Neuropsychological and neurophysiological consequences of partial callosotomy.

Sixty-five patients with lesions affecting the third ventricle (54 patients) or the corpus callosum itself (11 patients) underwent partial callosotomy or a circumscribed callosal resection. Before the surgery 20 patients were studied using the battery of cognitive, affective and behavioural tests which was repeated 10 and 100 days after surgery. No disconnection syndrome was over observed after the partial commissurotomy. Transcranial magnetic stimulation over the sensorimotor cortex was performed in 10 patients to determine conduction time of callosal fibres by measuring inhibition of tonic voluntary electromyographic activity in muscle's ipsilateral to the activated hemisphere. It was found that this inhibition was absent in patients with lesions of the trunk of the corpus callosum and present in patients with lesions of the genu or splenium. In addition magnetic resonance imaging measurements of the corpus callosum were performed in 40 normal subjects to establish a classification system for corpus callosal area. The results showed a wide variability of the cross-sectional area of the corpus callosum. The comparison of the shape of the corpus callosum lead to a categorisation according to the presence and location of depressions on its surface.

Brain Neoplasms↗

The effect of callus removal on dynamic plantar foot pressures in diabetic patients.

Clinical observation suggests that neuropathic foot ulceration frequently occurs beneath plantar callosities and in areas of high dynamic shear and vertical stress underneath the foot during walking. Seventeen diabetic patients had dynamic foot pressure measurements made before and after the removal of a total of 43 forefoot plantar callosities. Peak pressures (mean +/- SE) in the treated areas were reduced by 26% from 14.2 +/- 1.0 to 10.3 +/- 0.9 kg cm-2 (p less than 0.001), with reductions at 37 of the 43 sites and in all patients. Mean heel pressures were not significantly different (5.0 +/- 0.6 vs 4.9 +/- 0.6 kg cm-2). These results suggest that callus may act as a foreign body elevating plantar pressures and that a significant reduction in pressure is achieved by local chiropody treatment.

Analysis of Variance↗

Comparison of Viscoped and PORON for painful submetatarsal hyperkeratotic lesions.

A clinical study was performed to evaluate the efficacy of the Viscoped Insole as compared with an 1/8-inch PORON medical materials insole in the treatment of lesser submetatarsal hyperkeratotic callosities. Thirty-five patients, ranging in age from 23 through 61 years (average 42 years) were randomly divided into three groups. All three groups initially had debridement of their submetatarsal callosities. In addition to the debridement, the first group (16 patients) wore a Viscoped Insole for 4 weeks. The patients in the second group wore a PORON insole for 4 weeks. The third group did not receive an insole after their debridement and served as the control. There was a significant improvement in the Viscoped group and the PORON group versus the control group (x2 = 40; p < 0.01) as measured by the foot function index. Insole therapy combined with debridement for submetatarsal hyperkeratoses is more effective than debridement alone.

Callosities↗

Hairdresser's hand.

Thirty hairdressers working in small salons (maximum 10 employees) and two barbers were examined, with special attention being given to their hands. As many as 22 of the 32 subjects were found to have hand dermatitis, nail disorders or callosities on the fingers, while the remaining ten had no signs of such occupational skin disorders. Softening scaling and curving of the finger nails was found in 17, dermatitis on the knuckles and in the fingerwebs and adjacent skin areas in 12, and callosities in 5 persons. The disorders caused some discomfort but no absence from work to the persons affected. Irrelevant nickel allergy was encountered in two persons and paraphenylenediamine allergy in one. Inactive atopic disorders were noted in 8 persons but they atopy showed no correlation with the presence of hand dermatitis.

Adult↗

Posttraumatic cerebral hemispheric disconnection syndrome.

Gross and microscopic lesions of the corpus callosum and neighboring structures are common in severe closed head injury. This report is the first, to our knowledge, to confirm neuropathologically the occurrence of extensive traumatic destruction of the corpus callosum in a patient with left-sided apraxia and agraphia. It also demonstrates that large traumatic lesions of the corpus callosum may occur without prolonged posttraumatic coma, vegetative state, or death. In our patient, coexisting extracallosal hemispheric lesions may have modified the effects of callosal pathology. Cases of this type may be more common than generally appreciated, but since symptoms of hemispheric disconnection are not apparent in ordinary behavior, specific tests of callosal function must be employed if disconnection phenomena are to be detected in the posttraumatic period.

Aged↗

Small-diameter nonmyelinated axons in the primate corpus callosum.

The splenium of the corpus callosum of a primate (Macaca mulatta), examined with the electron microscope, was found to contain both myelinated and nonmyelinated axons. The majority of nonmyelinated axons had diameters of less tha 0.25 micron. On the basis of this diameter distribution, it is expected that many callosal axons conduct impulses at velocities of less than 1 m/s and that interhemispheric conduction times for some callosal axons are at least 30 ms and possibly much longer.

Animals↗

Cerebral disconnection in multiple sclerosis. Relationship to atrophy of the corpus callosum.

Left ear suppression to dichotically presented verbal stimuli has been observed in patients with multiple sclerosis (MS). Rubens and coworkers have suggested that a disconnection of the auditory callosal pathways may account for this finding. To examine this proposal, we compared the performance of 28 MS patients with significant corpus callosum atrophy (CCA) on midsagittal magnetic resonance scans, 16 MS patients without significant CCA, and 64 demographically matched normal control subjects on two laterality tasks: verbal dichotic listening (consonant-vowel syllables) and tachistiscopic object-naming latency. Results indicated that left ear suppression was found only in the MS patients with CCA. Likewise, patients in the MS group with CCA were slow in responding to stimuli presented in the left visual field; this effect was not observed in patients without CCA. These findings support the hypothesis that efficiency of cross-callosal information flow is reduced in MS patients with CCA.

Adult↗

Cortical connections of striate and extrastriate visual areas in tree shrews.

The ipsilateral and contralateral cortical connections of visual cortex of tree shrews (Tupaia belangeri) were investigated by placing restricted injections of fluorochrome tracers, wheat germ agglutinin-horseradish peroxidase, or biotinylated dextran amine into area 17 (V1), area 18 (V2), or the adjoining temporal dorsal area (TD). As previously reported, V1 was characterized by a widespread, patchy pattern of intrinsic connections; ipsilateral connections with V2, TD, and to a lesser extent, other areas of the temporal cortex; and contralateral connections with V1, V2, and TD. A surface-view of the myelin pattern in V1 revealed a patchwork of light and dark module-like regions. The ipsilateral connections with V2 and TD were roughly topographic, whereas heterotopic locations in V1 were callosally connected. Injections in V2 labeled as much as one third of V2 in a patchy pattern, and portions of ipsilateral V1 and TD in roughly topographic patterns. In addition, connections with several other visual areas in the temporal lobe were revealed. Contralaterally, most of the label was in V2, with some in V1 and TD. Injections in TD demonstrated connections within the region, and with adjoining portions of the temporal cortex, V2, and V1. There were sparse connections with an oval of densely myelinated cortex, which we have termed the temporal inferior area (TI). Callosal connections were concentrated in TD, but also included V2. The results provide further evidence for modular organizations within V1 and V2, and reveal for the first time the complete patterns of cortical connections of V2 and TD. The results are consistent with the proposal that at least three visual areas, the temporal anterior area, TA, the temporal dorsal area, TD, and the temporal posterior area, TP, exist along the rostrolateral border of V2 in tree shrews; suggest visual involvement of at least three other areas, the temporal inferior area, TI, the temporal anterior lateral area, and the temporal posterior inferior area located more ventrally in the temporal cortex; and fortify the conclusion that TD is the likely homologue of the middle temporal visual area of primates. Because tree shrews are considered close relatives of primates, the evidence for several visual areas along the border of V2 is more compatible with theories that propose a series of visual areas along V2 in primates, rather than a single visual area, V3.

Animals↗

Retarded formation of the hippocampal commissure in embryos from mouse strains lacking a corpus callosum.

A precise description of the timing and route traveled by axons traversing the telencephalic midline through the ventral hippocampal commissure (HC) is essential for understanding the role it plays in the formation of the corpus callosum (CC). A normal baseline of HC development was described in B6D2F2 hybrid mice and then compared with two inbred strains of mice displaying callosal agenesis, BALB/cWah1 (50% CC defect) and 129/J (70% CC defect), their F2 hybrid (C129F2-33% CC defect), and a recombinant inbred strain (RI-1-100% CC defect) derived from pairs of C129F2 mice. Embryos weighing from 0.25 g to 0.70 g (E14.5-E17) were collected and fixed by perfusion. Axon tracts were labeled using crystals of the lipophilic dyes DiI and DiA inserted into the hippocampal fimbria and cerebral cortex. HC axons in B6D2F2 mice first cross the midline at about 0.350 g body weight (E14.8) by traveling over the dorsal septum and along the pia membrane lining the longitudinal fissure. Earlier crossing was prevented by the presence of a deep cleft formed by the longitudinal fissure extending down into the septal region. Subsequent axons fasciculated along existing axons, gradually building the dorsoventral height of the HC to about 200 microns by 0.600 g. The earliest callosal axons from frontal cortex crossed the midline at 0.620 g and were clearly seen fasciculating along and between existing hippocampal axons at the dorsal surface of the HC as they crossed. In the acallosal strains, HC formation was delayed by the continued presence of the cleft deep in the septal region. This delay in time of crossing was correlated with later CC defect expression. Initial HC crossing occurred at about 0.470 g (E16.25) in BALB mice and about 0.520 g (E16.5) in 129 mice. In the RI-1 embryos, first HC crossing was estimated at about 0.750 g (E17.5), although several older embryos showed no crossing. These results show the importance of the HC for successful CC formation and suggest that absent CC arises as a consequence of a developmental defect which affects the formation of the hippocampal commissure prior to arrival of CC axons at midplane.

Agenesis of Corpus Callosum↗

Axosomatic input to subpopulations of cortically projecting pyramidal neurons in primate prefrontal cortex.

Pyramidal cells, the major class of cortical excitatory neurons, can be divided into different subpopulations based upon the target region of their principal axon projection. The activity of pyramidal neurons is regulated in part through inhibitory synaptic inputs to the soma from local circuit neurons. However, little is known about how the density of these axosomatic inputs differs among subpopulations of pyramidal neurons in the prefrontal cortex of primates. In this study, retrograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was used to identify pyramidal neurons in monkey prefrontal cortex (areas 9 and 46), which were labeled via either associational (ipsilateral hemisphere) or callosal (contralateral hemisphere) principal axon projections. Ultrastructural analysis revealed that the relative number of terminals apposed to the somatic membrane did not differ between associational and callosal neurons. However, neurons in the supragranular layers were apposed by a significantly greater number of axon terminals than were neurons in the infragranular layers. These findings suggest that the laminar environment of a neuron may play a more important role than principal axon projection in determining the amount of axosomatic inhibitory input it receives.

Analysis of Variance↗

Asymmetries of cerebral neuroanatomy.

The mammalian cerebral cortex is asymmetrical. One hemisphere does not contain cortical areas or architectonic patterns, histological features, ultrastructural characteristics, or connectivities of the neurons that are not present in the other: homologous areas on the two sides may differ only in size. Asymmetry has directionality: two-thirds of human brains have plana temporale that are larger on the left. Conversely, roughly the same number of non-human brains show asymmetry in one direction as in the other. Asymmetry has magnitude: some brains show a large asymmetry, others show no asymmetry in a given area. Symmetrical areas are larger than their asymmetrical counterparts, which reflects fewer neurons in the latter. Indirect evidence points to variable asymmetry in the germinal zones in the production of symmetrical or asymmetrical cortical areas. These areas differ in their patterns of callosal connections. Fewer connections are seen in the asymmetrical cases, paralleling the smaller number of neurons. The symmetrical cases contain connections that are more widely distributed. These findings of different numbers of neurons and different proportions of callosal connections suggest that symmetrical and asymmetrical cortical areas may have different functional properties.

Alzheimer Disease↗

Lipoma of corpus callosum associated with dysraphic lesions and trisomy 13.

We report on a further case of corpus callosal lipoma and frontal cranial defects. Most cases in the literature of corpus callosal lipoma in association with "dysraphic" lesions have been frontal in location. Malformation of the corpus callosum is said to be associated with 50% of these lipomas. Trisomy 13 was confirmed by the 13q14 cosmid probe on paraffin-embedded liver tissue.

Adult↗

Corpus callosum in sexually dimorphic and nondimorphic primates.

The midsagittal area and other morphological measures were taken on the corpus callosum of four different species of primate: Macaca mulatta, M. fascicularis, Callithrix jacchus, and Saguinus oedipus. The first two species are strongly dimorphic, whereas the New World forms show little dimorphism with regard to overall body size, canines, and brain weight. Neither total corpus callosal area (TOTALCC), or other parts of the corpus callosum (CC) showed any significant sexual dimorphism in any of the primate species sampled. Only in M. mulatta did a sexual dimorphism appear to be significant. In males of this species, the dorsoventral width of the splenium was larger than in females. In addition, the anterior commissure (ANTCOMM) evinced no sexual dimorphism in the different species. Brain weight was significantly dimorphic in only M. mulatta, and when ratio data were used to correct for brain weight, no significant differences were found in the corpus callosum. This is in contrast to Homo sapiens, where the relative size of the CC has been reported to be larger in females, and particularly so in the posterior, or splenial portion of the CC. Correlation coefficients were calculated for the various variables within each species. In general, most of the callosal measures are significantly inter-correlated, although the exact pattern varies for each species. Thus, unlike Homo sapiens, or pongids such as Gorilla and Pan, neither New nor Old World monkeys show any striking evidence for sexual dimorphism in the corpus callosum.

Animals↗

Sexual dimorphism of the human corpus callosum from three independent samples: relative size of the corpus callosum.

Three independent autopsy samples of brains without apparent neuropathology were studied to ascertain whether there was sexual dimorphism in the human corpus callosum (CC). Using planimetric measurements on midsagittal brain sections, several morphometric features of the CC were studied: total callosal area, maximum dorsoventral splenial width, the posterior one fifth of the total area of the CC (mostly splenium), and brain weight. Ratio data correcting for brain size were also studied. In all samples, absolute brain size was larger in males, and significantly so. Measurements of splenial dorsoventral width were higher in females than males, but not significantly, except in the Australian sample. Total callosal area was absolutely higher in the Australian female sample than in males, and almost equal in the two American samples, without statistically significant differences. The posterior one-fifth area (splenium) was larger for females in each of the samples. The variables which were corrected for brain size were usually significantly larger in females, although this pattern varied in each sample. The statistical pattern of sexual dimorphism for the human CC differs from that found in most other neural structures, such as the amygdaloid nucleus, cerebellum, hippocampus, and thalamus. The absolute sizes of these structures are always significantly larger in males. When corrected for brain size, the relative sizes are not significantly larger. The CC is the only structure to show a larger set of relative measures in females.

Adolescent↗

Absence of transcallosal inhibition following focal magnetic stimulation in preschool children.

Focal transcranial magnetic stimulation of the hand-associated motor cortex was used to study normal healthy preschool children (n = 7; mean age, 4.6 years) and adults (n = 7; mean age, 29.4 years) under the conditions of standardized tonic voluntary contraction of small hand muscles. Callosally mediated inhibitory as well as corticospinally mediated inhibitory and excitatory motor effects were investigated. Although children had no detectable transcallosal inhibition, their corticospinally mediated postexcitatory silent period was present (mean, 140.8 +/- 30.2 msec). It was significantly shorter than in adults (mean, 192.5 +/- 32.0 msec). The motor thresholds of the cortically elicited muscle responses, measured as the lowest stimulus intensity, were significantly higher in children (mean, 89 +/- 5%) than in adults (mean, 46 +/- 6%). The corticomuscular latency of transcranially elicited motor responses revealed no difference between children and adults. These observations may reflect maturation processes in the motor system. Maturation of at least some direct corticospinal fibers occurs early in life and is followed by that of intracortical excitatory and inhibitory connections. The maturation of functionally competent callosal connections appears to occur after the age of 5 years.

Adult↗