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PubMed1991

Organization of ascending hypothalamic projections to the rostral forebrain with special reference to the innervation of cholinergic projection neurons.

Axonal projections from hypothalamic nuclei to the basal forebrain, and their relation to cholinergic projection neurons in particular, were studied in the rat by using the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in combination with choline acetyltransferase (ChAT) immunocytochemistry. Discrete iontophoretic PHA-L injections were delivered to different portions of the caudal lateral hypothalamus, as well as to various medial hypothalamic areas, including the ventromedial, dorsomedial, and paraventricular nuclei, and anterior hypothalamic and medial preoptic areas. The simultaneous detection of PHA-L-labeled fibers/terminals and ChAT-positive neurons was performed by using nickel-enhanced diaminobenzidine (DAB) and nonenhanced DAB as chromogens. Selected cases were investigated at the electron microscopic level. Ascending hypothalamic projections maintained an orderly lateromedial arrangement within the different components of the medial forebrain bundle, as well as with respect to their terminal projection fields (e.g., within the bed nucleus of the stria terminalis and lateral septal nucleus). The distribution pattern of hypothalamic inputs to cholinergic projection neurons corresponded to the topography of ascending hypothalamic axons. Axons originating from neurons in the far-lateral hypothalamus reached cholinergic neurons in a zone that extended from the dorsal part of the sublenticular substantia innominata (SI) caudolaterally, to the lateral portion of the bed nucleus of the stria terminalis rostromedially, encompassing a narrow band along the ventral part of the globus pallidus and medial portion of the internal capsule. Axons originating from cells in the medial portion of the lateral hypothalamus reached cholinergic cells primarily in more medial and ventral parts of the SI, and in the magnocellular preoptic nucleus and horizontal limb of the diagonal band nucleus (HDB). Axons from medial hypothalamic cells appeared to contact cholinergic neurons primarily in the medial part of the HDB, and in the medial septum/vertical limb of the diagonal band complex. Electron microscopic double-labeling experiments confirmed contacts between labeled terminals and cholinergic cells in the HDB and SI. Individual hypothalamic axons established synapses with both cholinergic and noncholinergic neuronal elements in the same regions. These findings have important implications for our understanding of the organization of afferents to the basal forebrain cholinergic projection system.

Afferent Pathways↗
PubMed1991

Prefrontostriatal connections in relation to cortical architectonic organization in rhesus monkeys.

Prefrontostriatal connections were investigated in rhesus monkeys using the autoradiographic technique to examine whether there are systematic relationships with regard to the architectonic organization of the prefrontal cortex. On the basis of progressive laminar elaboration, the different regions of the prefrontal cortex can be grouped into two architectonic trends. The dorsal trend, which begins in the medial proisocortical areas, can be followed through the dorsolateral prefrontal cortex, culminating in the dorsal arcuate region. The ventral trend, which originates in the orbital proisocortex, can be traced through the inferior prefrontal convexity to the ventral arcuate region. The results show that the main connections from the prefrontal cortex to the striatum are to the head and body of the caudate nucleus. These connections are topographically organized. Medial and dorsal prefrontal areas project predominantly to the dorsal and central portion of the head and body of the caudate nucleus, whereas orbital and inferior prefrontal areas are related mainly to the ventral and central portion. Moreover, prefrontostriatal connections have a medial-lateral topography. Medial and orbital prefrontal areas project medially in the head and body of the caudate nucleus, whereas the dorsal and ventral arcuate regions project laterally, adjacent to the internal capsule. The prefrontal regions above and below the principal sulcus project mainly to the intermediate sector of the head and body of the nucleus. However, there appears to be some degree of overlap of corticostriatal projections from the dorsal and ventral prefrontal regions, as well as within each trend. Relatively minor projections are directed to the putamen as well as to the tail of the caudate nucleus from certain subregions of the prefrontal cortex. Thus the distribution of prefrontostriatal connections seems to reflect the architectonic organization of the prefrontal cortex. Possible functional aspects of prefrontostriatal connectivity are considered in the light of behavioral and physiological studies.

Animals↗
PubMed1991

Immunocytochemical localization of argininosuccinate synthetase in the rat brain.

The neuronal distribution of argininosuccinate synthetase (ASS) was mapped in the rat brain. Argininosuccinate synthetase is one of the enzymes of the arginine metabolic pathway and catabolizes the synthesis of argininosuccinate from aspartate and citrulline. Since arginine is the precursor of nitric oxide, argininosuccinate synthetase may act as part of the nitric oxide producing pathway. Argininosuccinate is also suggested to have a messenger function in the nervous system. Therefore, the localization of ASS is of great interest. Polyclonal antisera against purified rat liver argininosuccinate synthetase revealed a characteristic distribution pattern of argininosuccinate synthetase-like immunoreactivity: (1) many neurons with strong argininosuccinate synthetase-like immunoreactivity were observed in the septal area, basal forebrain, anterior medial and premammillary nuclei of the hypothalamus, anterior and midline thalamic nuclei, dorsal endopiriform nucleus of the amygdala, basal nucleus of Meynert, subthalamic nucleus, laterodorsal tegmental nucleus, raphe nuclei, nucleus ambiguus, and the area postrema, (2) neuropile staining was dense in the septal areas, hypothalamus, area postrema, nucleus of the solitary tract, and the laminae I and II of the caudal subnucleus of the spinal trigeminal nucleus and the spinal dorsal horn, (3) relay nuclei of the specific sensory systems such as the dorsal lateral geniculate nucleus and the ventral nuclei of the thalamus were devoid of argininosuccinate synthetase-like immunoreactivity, (4) no staining was seen in the large white matter structures such as the internal capsule, corpus callosum, and the anterior commissure, and (5) most of the neurons stained were small or medium in size and appeared to be interneurons. The results suggest that argininosuccinate synthetase affects the widely distributed, neuromodulatory system in the brain.

Animals↗
PubMed1992

Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a PHA-L study of subcortical projections.

The subcortical projections of the centromedian (CM) and the parafascicular (Pf) thalamic nuclei were examined in the squirrel monkey (Saimiri sciureus) by using the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) as an anterograde tracer. Both CM and Pf project massively to the striatum where they arborize in a complementary fashion. On the one hand, CM innervates most of the putamen caudal to the anterior commissure, a dorsolateral rim of the putamen rostral to the anterior commissure, discrete areas of the head of the caudate nucleus close to the internal capsule, and a lateral sector of the body of the caudate nucleus. On the other hand, Pf provides a heavy input to the head, body, and tail of the caudate nucleus, and to the rostral putamen, excluding the areas innervated by CM. In addition, Pf projects more discretely to the nucleus accumbens and the olfactory tubercle. Therefore, the projections from both CM and Pf cover the entire striatum, with those from CM arborizing into the "sensorimotor" striatal territory and the ones from Pf innervating the "associative-limbic" striatal territory. Furthermore, CM and Pf project to extrastriatal subcortical structures, such as the globus pallidus, the subthalamic nucleus, and the substantia nigra, where they also terminate in a complementary fashion. Topographically and cytologically, Pf is closely related to the subparafascicular nucleus (sPf). The Pf-sPf complex projects to the hypothalamus, the substantia innominata, the peripeduncular nucleus, and the amygdala. It also gives rise to descending efferents arborizing in various brainstem structures, including the inferior olivary complex. Additional studies with retrograde double-labeling methods show that distinct cell groups within CM project to the motor cortex and the striatum. Likewise, separate neuronal populations within the CM-Pf-sPf complex give rise to striatal and brainstem projections, the former arising from CM and Pf and the latter mainly from sPf. The complementary nature of CM and Pf projections to the striatum and other basal ganglia components suggests that this thalamic complex participates in a highly ordered manner in the parallel processing of the information that flows through the basal ganglia.

Afferent Pathways↗
PubMed1992

Course of the fiber pathways to pons from parasensory association areas in the rhesus monkey.

The course of the fiber pathways to pons from parasensory association areas in the rhesus monkey was investigated by injection of tritiated amino acids and the technique of autoradiography. Results confirm the projection to pons from parasensory association areas in the temporal, parietal, and occipital lobes and extend these observations to include the posterior parahippocampal gyrus. The findings reveal that the white matter of the posterior limb of the internal capsule above the midpoint of the lateral geniculate nucleus, and at the medial aspect of the lateral geniculate nucleus, comprise common regions through which these corticopontine fibers lead to the basis pontis. The fibers demonstrate a certain degree of topographic organization in the posterior limb of the capsule above the lateral geniculate nucleus and also in the cerebral peduncle. Taken together with previous observations concerning the termination patterns of these associative corticopontine projections, it would appear that the corticopontine system consists of segregated and partially overlapping pathways, which are to some extent distinguishable anatomically at each stage of their trajectory from origin to destination. Furthermore, the existence of a common area through which all parasensory associative input to pons is transmitted suggests that a precisely located lesion in this part of the corticopontocerebellar circuit may disrupt the cerebellar access to higher order information derived from the parasensory associative regions.

Animals↗
PubMed1992

Development of GABA-immunoreactivity in the neocortex of the mouse.

The prenatal and postnatal development of GABAergic elements in the neocortex of the mouse was analyzed by GABA-immunocytochemistry. Radial distribution of cells and laminar numerical densities were calculated at each developmental stage to substantiate qualitative observations. The first immunoreactive neurons were observed in the cortical anlage at embryonic day 12-embryonic day 13 (E12-E13) in the primitive plexiform layer. At following prenatal stages (E14-E19), most GABA-positive neurons were present in the marginal zone, subplate, and subventricular zone. GABA-immunoreactivity in the cortical plate appeared early (E14), although the complete maturation of its derivatives was achieved postnatally. At prenatal stages we noted a well-developed system of immunopositive fibers in the subplate. As indicated by the direction of growth cones, most of these fibers had an extracortical origin and invaded the cortex laterally through the internal capsule and striatum. In rostral and middle telencephalic levels, fibers originating in the septal region contributed to the cingulate bundle. Presumably corticofugal fibers and callosal axons were also noticed. At postnatal stages the maturation of GABA-immunoreactivity appeared to be a complex, long-lasting process, in which the adult pattern was produced at the same time as the appearance of certain regressive phenomena. Thus, between postnatal day 0 and postnatal day 8 (P0-P8), GABA-positive populations disappeared from the subventricular zone, marginal zone and to a lesser extent from the subplate. At the same ages we noticed the presence of morphologically abnormal, GABA-immunoreactive neurons in the subventricular zone and subplate which are interpreted as correlates of neuronal degeneration. Most GABA-positive subplate fibers also disappeared whereas GABA-immunoreactive axons were seen in the cingulate bundle until the adult stage. In the derivatives of the cortical plate, the maturation of GABA-immunoreactive elements progressed according to the "inside-out" gradient of cortical development, with the important exception of layer IV, which was the last layer to exhibit an adult-like appearance. Within each layer deriving from the cortical plate (layers VIa to II-III), GABA-immunoreactivity showed a protracted maturation in which the first GABA-positive cells were detected a few days after cell birth but substantial numbers of neurons began to express GABA considerably later. The later phase occurred concurrently with the maturation of GABA-positive axonal plexuses. These results suggest that different GABA-positive populations show different developmental regulation of GABA expression during cortical ontogenesis.

Aging↗
PubMed1993

The early development of thalamocortical and corticothalamic projections.

The early development of thalamocortical and corticothalamic projections in hamsters was studied to compare the specificity and maturation of these pathways, and to identify potential sources of information for specification of cortical areas. The cells that constitute these projections are both generated prenatally in hamsters and they make reciprocal connections. Fluorescent dyes (DiI and DiA) were injected into the visual cortex or lateral geniculate nucleus in fixed brains of fetal and postnatal pups. Several issues in axonal development were examined, including timing of axon outgrowth and target invasion, projection specificity, the spatial relationship between the two pathways, and the connections of subplate cells. Thalamic projections arrive in the visual cortex 2 days before birth and begin to invade the developing cortical plate by the next day. Few processes invade inappropriate cortical regions. By postnatal day 7 their laminar position is similar to mature animals. By contrast, visual cortical axons from subplate and layer 6 cells reach posterior thalamus at 1 day after birth in small numbers. By 3 days after birth many layer 5 cell projections reach the posterior thalamus. On postnatal day 7, there is a sudden increase in the number of layer 6 projections to the thalamus. Surprisingly, these layer 6 cells are precisely topographically mapped with colabeled thalamic afferents on their first appearance. Subplate cells constitute a very small component of the corticothalamic projection at all ages. Double injections of DiI and DiA show that the corticofugal and thalamocortical pathways are physically separate during development. Corticofugal axons travel deep in the intermediate zone to the thalamic axons and are separate through much of the internal capsule. Their tangential distribution is also distinct. The early appearance of the thalamocortical pathway is consistent with an organizational role in the specification of some features of cortical cytoarchitecture. The specific initial projection of thalamocortical axons strongly suggests the recognition of particular cortical regions. The physical separation of these two pathways limits the possibility for exchange of information between these systems except at their respective targets.

Afferent Pathways↗
PubMed1993

Development of geniculocortical projections to visual cortex in rat: evidence early ingrowth and synaptogenesis.

Anterograde movement of DiI and transneuronal transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were used to study the temporal and laminar patterns of ingrowth of the geniculocortical projection to visual cortex in fetal and postnatal rats. The development of this projection was compared to patterns of migration and settling of [3H]-thymidine-labeled neurons destined for cortical layer IV, and to geniculocortical synapse formation. DiI-labeled geniculocortical axons were found in the intermediate zone beneath the lateral cerebral mantle at embryonic day (E)17 and in the subplate layer underlying visual cortex by E18. On E19 they appeared to accumulate and grow radially into an expanding subplate layer and into the deep part of developing cortical layer VI. By postnatal day (P)0, DiI or WGA-HRP-labeled geniculocortical axons were found in developing cortical layers VI and V. By P1, they invaded the deep portion of the cell-dense cortical plate, where they were in position to make initial contact with neurons that would later form layer IV. A few axons traversed the cortical plate to reach the marginal zone. Layer IV became an identifiable layer on P2, and a clear projection to layer IV was evident by P3. These results suggest that geniculocortical afferents grow continuously from the intermediate zone, initially into an expanding subplate layer and then sequentially into each of the developing cortical layers without evidence of "waiting." Electron microscopic data suggest that geniculocortical axons begin to form immature synapses with dendrites and neuronal perikarya as they first encounter cortical neurons, first in the subplate layer and then in developing layers VI, V and marginal zone, in addition to the primary target layer IV. The precise targeting and overall temporal and laminar patterns of ingrowth and synaptogenesis suggest that geniculocortical axons are directed to the visual cortex by guidance cues within the internal capsule and subplate. Further, they reach the occipital pole early enough to influence the specification and histogenesis of cortical area 17, perhaps by exerting an influence on the deep-to-superficial "wave" of neuronal differentiation in sequentially developing subplate and cortical layers VI, V and IV.

Afferent Pathways↗
PubMed1993

Stathmin: cellular localization of a major phosphoprotein in the adult rat and human CNS.

Stathmin is a ubiquitous, 19 kDa cytoplasmic protein the phosphorylation of which is associated with many cellular signaling pathways. It is particularly abundant in neurons and reaches a peak of expression in the neonatal period, although it remains highly expressed in the adult brain. In order to determine whether this abundant expression is associated with discrete cellular populations that are still at an immature stage during adulthood, as suggested by others, the cellular localization of stathmin was investigated in the adult rat and human central nervous system. Western blotting with a specific antiserum indicated that stathmin was ubiquitous in the brain and spinal cord but that its relative concentration varied up to 2.6 times between regions. To characterize the distribution of stathmin within the brain, its cellular localization was analyzed by immunocytochemistry. Highly immunoreactive neurons and oligodendrocytes were observed, and stathmin immunoreactivity was localized to the perikaryon and all processes, but not the nucleus. Most brain and spinal cord cell groups showed stathmin immunoreactivity, although the extent and intensity of labeling differed largely from one place to another. Particularly numerous stathmin-immunoreactive neuronal cell bodies were found in the pyriform, cingulate, and neocortex, as well as in many cholinergic nuclei of the basal forebrain and brainstem, in the medial thalamus, in various brainstem nuclei, in the dorsalmost layers of the spinal cord, and in brain areas lacking a blood-brain barrier to macromolecules. In addition to neuronal populations, stathmin-antibodies intensely labeled choroid plexuses. Many other brain regions exhibited moderate neuronal immunostaining. The distribution of stathmin-immunoreactive processes was in some areas relatively heterogeneous. Intense immunoreactivity was observed in some fiber tracts (corpus callosum, anterior commissure, inferior cerebellar peduncle, etc.) but was missing in others (internal capsule, posterior commissure, etc.). Some brain areas rich in immunoreactive neurons also displayed an intense immunoreactivity of the neuropile, whereas others contained either immunoreactive cells or fibers. In the human brain, stathmin immunostaining occurred in many areas, corresponding to those identified in the rat, with the exception of the cerebral cortex, the hippocampal fascia dentata, and the substantia nigra. The present results support our suggestion that, in addition to its involvement in cell proliferation and differentiation, stathmin may also be related to regulation of differentiated cell functions, as it appears to be a major signaling protein in widespread areas of the adult brain in both rat and human.

Aged↗
PubMed1993

Development of the thalamic reticular and perireticular nuclei in rats and their relationship to the course of growing corticofugal and corticopetal axons.

This study examines the connections of the thalamic reticular and perireticular nuclei during development. In addition, because these nuclei lie directly in the path of corticofugal and corticopetal axons during development, we have examined the relationship of these growing axons to the reticular and perireticular cell groups. Neurones were labelled by applying DiI, wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), or HRP to the dorsal thalamus and/or cerebral cortex of rats at different stages of development. The axons of neurons in the reticular nucleus reach the dorsal thalamus as early as embryonic day (E) 14. At this age, and during later prenatal development, a small DiI implant limited to the presumptive lateral geniculate nucleus labels reticulothalamic and thalamocortical axons which travel in a clearly defined bundle through the thalamus. During late gestation, thalamocortical (approximately E15) and corticothalamic (approximately E17) axons pass directly through the reticular nucleus toward their targets. It is not until birth that collaterals are seen extending into the nucleus from the parent axons. Neurones in the perireticular nucleus, in contrast to those in the reticular nucleus, are not labelled from the lateral geniculate nucleus until after birth. The perireticular nucleus is very large at a stage when the first thalamocortical axons leave and when the first corticothalamic axons approach the thalamus. These axons are seen to change course sharply in the region of the internal capsule, where there are many perireticular cells. Corticothalamic axons turn toward the reticular nucleus, and thalamocortical axons turn toward the cortical subplate. Corticospinal and corticobulbar axons, on the other hand, pass directly through the perireticular region toward their more caudal targets. After these axons have reached their targets, the perireticular nucleus reduces dramatically in size.

Afferent Pathways↗
PubMed1994

Morphological maturation of thalamic neurons as studied in fetal neural transplants.

This study attempts to determine whether fetal thalamic neuroblasts from rat embryos (embryonic age 15 days) labeled with horseradish peroxidase (HRP) can differentiate into their normal dendritic phenotype when transplanted as a cell suspension into a lesioned site in the adult somatosensory thalamus. The HRP labeling provided a Golgi-like staining of numerous neurons up to 12-14 days after transplantation. There were three main results. 1) As early as 2 days after transplantation three morphologic cell types were observed: Two were bipolar and the third multipolar. These cellular profiles are characteristic of adult ventroposterolateral, reticular, and ventroposteromedial neurons and suggest that transplanted neurons can take shape in the absence of specific arrangements of afferent fibers. 2) The initial stage of dendritic growth was characterized by numerous growing specializations and consisted of a rapid, arborizing growth that appeared to proceed at an accelerated rate relative to normal development. During the later stage, which was characterized by the great reduction of growing specializations, dendritic remodeling resulted in a simpler morphology, and the transplanted neurons did not achieve an adult morphology. 3) Putative axons exhibiting growth cones were present in impressive densities in the transplants, and a number of them grew into the neuron-depleted host thalamus. A very small number of axons grew into host gray matter outside the lesioned area, indicating that neurodegenerative areas provide a better substrate for neurite outgrowth than intact tissue. In rare instances axons were visible in the internal capsule, indicating that the biochemical inhibition provided by mature myelin and oligodendrocytes may not be an absolute obstacle to axonal growth.

Afferent Pathways↗
PubMed2026

Awake Craniotomy for Eloquent Region Glioblastoma Classified by Tumor Location-A Retrospective and Prospective Cohort Study.

INTRODUCTION: The efficacy of awake craniotomy (AC) with intraoperative mapping for glioblastoma (GBM) in eloquent regions remains debated. This study aims to evaluate functional and survival outcomes of GBM patients undergoing AC stratified by tumor locations. METHODS: A combined retrospective (2015-2023, n = 114: 43 AC vs. 71 standard craniotomy) and prospective cohort (2023-2025, n = 28: 13 AC vs. 15 standard craniotomy) of GBM patients with motor/language-eloquent tumors was analyzed. Tumors were classified into motor subtypes (I: precentral gyrus; II: premotor/supplementary motor; III: internal capsule posterior limb; IV: other) and language subtypes (I: Broca's/precentral; II: postcentral/supramarginal gyrus; III: Wernicke's; IV: insular; V: other). Outcomes included extent of resection (EOR), postoperative motor/language recovery, overall survival (OS), and progression-free survival (PFS). RESULTS: The retrospective cohort demonstrated that AC has advantages in functional preservation across various motor/language subtypes. However, AC was associated with significantly deteriorated survival outcomes specifically in precentral gyrus GBMs. A prospective cohort study, enrolling only precentral gyrus GBMs for validation, yielded results consistent with the retrospective findings: worsened OS and PFS (OS: HR = 3.223, p = 0.0450; PFS: HR = 2.374, p = 0.0476); reduced EOR (AC: 74.3% ± 5.3%; standard craniotomy: 86.9% ± 12.3%, p = 0.0470); and better motor recovery. CONCLUSIONS: Functional preservation and survival outcomes of AC in GBM exhibited subtype-specific correlations with tumor locations. AC with intraoperative mapping effectively preserves neurological function in GBM patients. However, for tumors involving the precentral gyrus, the AC approach carries greater risks than benefits and should be considered with caution. TRIAL REGISTRATION: Strategic Intervention on Preserving Motor Function During Awake Craniotomy: NCT05143788. Strategic Intervention on Preserving Language Function During Awake Craniotomy: NCT05143775.

Adult↗
PubMed2003

Localization of aggrecan and versican in the developing rat central nervous system.

The localization of aggrecan and mRNA splice variants of versican in the developing rat central nervous system has been examined by using specific polyclonal antibodies to the nonhomologous glycosaminoglycan attachment regions of these hyaluronan-binding chondroitin sulfate proteoglycans. At embryonic day 16 (E16), aggrecan and versican splice variants containing either or both the alpha-and beta-domains are present in the marginal zone and subplate of the cerebral cortex and in the amygdala, internal capsule, and the optic and lateral olfactory tracts. There is strong staining of versican but not of aggrecan in the hippocampus and dentate gyrus by E19, whereas both aggrecan and alpha-versican are present in the fimbria. At E19, aggrecan is seen throughout the cerebral cortex, whereas the distribution of versican is considerably more limited, being confined essentially to the marginal zone and subplate. At 1 week postnatal, both aggrecan and versican are present in the prospective white matter and in the molecular and granule cell layers of the cerebellum, but neither proteoglycan is seen in the external granule cell layer. alpha- but not beta-versican staining is seen in Purkinje cells, and aggrecan staining of Purkinje cells is also rather minimal. In the spinal cord at E13, aggrecan is present in the dorsal root entry zone, ventral funiculus, mantle layer, and floor plate, as well as in the dorsal root ganglia and ventral roots. However, alpha-versican is confined to the dorsal root entry zone and the ependyma surrounding the spinal canal, and beta-versican is not present in spinal cord parenchyma at this developmental stage, being limited to the surrounding connective tissue. By E19, there are significant amounts of all three proteoglycans in the spinal cord. Aggrecan staining is most intense in the lateral funiculus and the fasciculi gracilis and cuneatus, where alpha-versican staining is also strong. In contrast, beta-versican is seen predominantly in the motor columns. Differences in the localization and temporal expression patterns of these chondroitin sulfate proteoglycans suggest that, like neurocan and phosphacan, they have partially complementary roles during central nervous system development.

Aggrecans↗
PubMed1993

Differential migration of astrocytes grafted into the developing rat brain.

Fetal and neonatal astrocytes migrate in specific patterns when transplanted into the adult rat host brain. However, it is unclear whether these astrocytes demonstrate the same degree of mobility during early brain development. In the present study, neonatal cortical, hippocampal, and hypothalamic astrocytes were collected from the brains of 1- to 3-day-old rats and placed in tissue culture. After 14 to 21 days, cultures enriched in astrocytes were harvested and labelled with either the fluorescent dye Fast Blue or fluorescein-labelled latex beads. They were then transplanted into the right frontal cerebrum of neonatal rats at 2, 5, 8, and 11 days postpartum. Seven days after transplantation, animals were sacrificed and their brains were fixed by immersion in aldehydes, sectioned on a cryostat, and examined with fluorescence microscopy. Transplanted astrocytes migrated along the corpus callosum, internal capsule, glial limitans, ventricular linings, and hippocampal structure. Labelled cells were also found in the contralateral hemisphere in day 2 brains. Migration in a radial fashion from the injection site toward the periphery was a particularly obvious pattern, and was most pronounced in these younger hosts. In days 5 and 8 rat brains, astrocyte migration became more restricted to the hemisphere of implantation. In 11-day-old host brains, hemispheric restriction and other region-specific influences became manifest and specifically modulated migration. Radial migration was absent in the 11-day-old host group except for cells of cortical origin. The observed results demonstrate that neonatal cortical, hippocampal, and hypothalamic astrocytes transplanted into the neonatal cerebrum migrate in patterns that are more extensive than in the adult brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

White matter tractography using diffusion tensor deflection.

Diffusion tensor MRI provides unique directional diffusion information that can be used to estimate the patterns of white matter connectivity in the human brain. In this study, the behavior of an algorithm for white matter tractography is examined. The algorithm, called TEND, uses the entire diffusion tensor to deflect the estimated fiber trajectory. Simulations and imaging experiments on in vivo human brains were performed to investigate the behavior of the tractography algorithm. The simulations show that the deflection term is less sensitive than the major eigenvector to image noise. In the human brain imaging experiments, estimated tracts were generated in corpus callosum, corticospinal tract, internal capsule, corona radiata, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto-occipital fasciculus, and uncinate fasciculus. This approach is promising for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship between major fiber trajectories and the location and extent of brain lesions.

Algorithms↗
PubMed2005

Formal characterization and extension of the linearized diffusion tensor model.

We analyzed the properties of the logarithm of the Rician distribution leading to a full characterization of the probability law of the errors in the linearized diffusion tensor model. An almost complete lack of bias, a simple relation between the variance and the signal-to-noise ratio in the original complex data, and a close approximation to normality facilitated estimation of the tensor components by an iterative weighted least squares algorithm. The theory of the linear model has also been used to derive the distribution of mean diffusivity, to develop an informative statistical test for relative lack of fit of the ellipsoidal (or spherical) model compared to an unrestricted linear model in which no specific shape is assumed for the diffusion process, and to estimate the signal-to-noise ratios in the original data. The false discovery rate (FDR) has been used to control thresholds for statistical significance in the context of multiple comparisons at voxel level. The methods are illustrated by application to three diffusion tensor imaging (DTI) datasets of clinical interest: a healthy volunteer, a patient with acute brain injury, and a patient with hydrocephalus. Interestingly, some salient features, such as a region normally comprising the basal ganglia and internal capsule, and areas of edema in patients with brain injury and hydrocephalus, had patterns of error largely independent from their mean diffusivities. These observations were made in brain regions with sufficiently large signal-to-noise ratios (>2) to justify the assumptions of the log Rician probability model. The combination of diffusivity and its error may provide added value in diagnostic DTI of acute pathologic expansion of the extracellular fluid compartment in brain parenchymal tissue.

Adult↗
PubMed2005

Using automated morphometry to detect associations between ERP latency and structural brain MRI in normal adults.

Despite the clinical significance of event-related potential (ERP) latency abnormalities, little attention has focused on the anatomic substrate of latency variability. Volume conduction models do not identify the anatomy responsible for delayed neural transmission between neural sources. To explore the anatomic substrate of ERP latency variability in normal adults using automated measures derived from magnetic resonance imaging (MRI), ERPs were recorded in the visual three-stimulus oddball task in 59 healthy participants. Latencies of the P3a and P3b components were measured at the vertex. Measures of local anatomic size in the brain were estimated from structural MRI, using tissue segmentation and deformation morphometry. A general linear model was fitted relating latency to measures of local anatomic size, covarying for intracranial vault volume. Longer P3b latencies were related to contractions in thalamus extending superiorly into the corpus callosum, white matter (WM) anterior to the central sulcus on the left and right, left temporal WM, the right anterior limb of the internal capsule extending into the lenticular nucleus, and larger cerebrospinal fluid volumes. There was no evidence for a relationship between gray matter (GM) volumes and P3b latency. Longer P3a latencies were related to contractions in left temporal WM, and left parietal GM and WM near the interhemispheric fissure. P3b latency variability is related chiefly to WM, thalamus, and lenticular nucleus, whereas P3a latency variability is not related as strongly to anatomy. These results imply that the WM connectivity between generators influences P3b latency more than the generators themselves do.

Adult↗
PubMedDate not supplied

The experience of recovery following lacunar stroke.

Little is known about the experience of recovery following stroke. A longitudinal, descriptive ethnography formed the basis of the study described in this article, in which 120 interviews were conducted over a period of 6 months with 13 individuals who had experienced lacunar infarcts of the internal capsule of the brain. Participants were interviewed within 72 hours of the infarct and during the acute and rehabilitation phases of recovery. This article discusses the experience of the recovering body and plateaus in this recovery, as well as the phenomena of experimentation with tasks, transformation by familiar surroundings, and sequential focus on involved limbs.

Activities of Daily Living↗