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Biomedical subjects

A M Galaburda

Publications and source records attributed to A M Galaburda.

At least 19 recordsLinked to original sources
PubMed1996

Birthdates of neurons in induced microgyria.

Freezing injury to the cortical plate of the newborn rat results in the formation of a focal region of cerebrocortical microdysgenesis resembling, in many ways, human 4-layered microgyria. Previous research has shown that neurons born during embryonic day (E) 20 migrate through the initial damage and take their place in the cell-dense layer of the microgyric lesion. The current study was conducted to determine: (1) whether neurons generated earlier in development would be found in microgyric cortex; and (2) whether the freezing injury would stimulate production of neurons postnatally. Rat pups from mothers who were injected with S-phase markers on E15, E17, E19, and E21 were subjected to freezing injury of the cortex to induce microgyria on postnatal day (P) 1. Other pups received a freezing lesion and then pulse or cumulative injections of S-phase markers for the next 72 h. Neurons born on E17 and E19 were found scattered throughout the cell-dense layer of the microgyric cortex. Early (E15) generated neurons were nearly absent in the microgyric cortex, and there was no evidence of postnatal induction of cortical neurogenesis. These results are considered in light of recent work demonstrating postnatal neocortical neurogenesis in response to early neocortical injury.

Aging↗
PubMed1996

Learning and memory in the autoimmune BXSB mouse: effects of neocortical ectopias and environmental enrichment.

Approximately 40-60% of BXSB mice have ectopic cell clusters in layer 1 of neocortex. Prior studies have shown distinct behavioral differences between those with ectopias and their non-ectopic littermates. In this study, female BXSB mice were reared after weaning in either enriched environments or standard cages. Following an initial round of behavioral testing, all mice were housed in standard cages and retested. Enriched cage mice (both ectopic and non-ectopic) showed increased activity, greater speed, and enhanced learning scores across a variety of tests. Additionally, prior test experience itself had significant positive effects on Hebb-Williams maze learning. The presence of ectopias resulted in better Morris maze learning for standard cage reared mice. Further, ectopic mice, regardless of their housing condition, showed better long-term retention in the Morris maze than did their non-ectopic counterparts. These findings show that abnormalities in corticogenesis need not always result in functional deficit.

Analysis of Variance↗
PubMed1996

Effects of embryo transfer and cortical ectopias upon the behavior of BXSB-Yaa and BXSB-Yaa + mice.

The BXSB-Yaa and BXSB-Yaa + inbred strains of mice differ primarily with respect to the Y chromosome, although there is evidence that they differ on several autosomal genes as well. Each strain has ectopic collections of neurons in neocortical layer I (ectopias), with a higher occurrence in males (58%) than females (42%). Conventionally reared mice from these strains were compared to mice that were transferred, as 8-cell embryos, into the uteri of non-autoimmune recipients, who gave birth to and reared the offspring. The transfer procedure did not change the incidence of ectopias in either sex. There were, however, major differences in behavior. Compared to conventionally reared controls, embryo transfer mice had greater behavioral asymmetry, poorer performance in a black-white discrimination, poorer Morris maze learning, better Lashley maze learning, and better performance in a two-way shuttlebox. Within the transfer groups, females differed as much as males, confirming our prior findings and supporting our thesis that the two strains differ on several autosomal genes in addition to the Y chromosome. These findings show that the intra-uterine environment can powerfully and selectively affect later behavior. When ectopic and non-ectopic mice were compared, BXSB-Yaa mice with neocortical ectopias were better able to learn the Morris spatial maze than non-ectopic controls; this was true whether the mice were conventionally reared or embryo transferred. In contrast, BXSB-Yaa + ectopic mice did not differ from their controls if conventionally reared, but were much worse than controls if embryo transferred.

Animals↗
PubMed1995

Behavioral consequences of neonatal injury of the neocortex.

Several strains of autoimmune mice spontaneously develop molecular layer ectopias that are similar in appearance to those seen in humans and are caused by disturbances in neocortical neuronal migration. These mice also exhibit behavioral anomalies, some of which correlate with ectopias, others with the immunological disorder. In this study, we induced neocortical ectopias (via puncture wounds) and microgyria (via freezing lesions) in the neocortex of 1-day-old (newborn) mice without immune disorders in an attempt to further disentangle the effects of autoimmunity and of cortical malformation on behavior. In addition, we wished to compare the behavioral effects of small ectopias to larger microgyric lesions. DBA mice were assigned at birth to receive either a puncture wound or freezing lesion of either the left or right hemisphere. An independent group was subjected to sham surgery. In adulthood, these mice were given a battery of tests designed to measure lateralization and learning capacity. Lesioned mice (irrespective of hemisphere or type of damage) performed poorly when compared to sham-operated animals in discrimination learning, in a spatial Morris Maze Match-to-Sample task, and in a Lashley Type III maze. In shuttlebox avoidance conditioning, where immunological disorder has been shown to compromise behavioral performance in autoimmune mice, there was no difference between lesioned and sham animals. These results (1) support the dissociation between the effects of developmental neocortical anomalies and autoimmune disease on behavior (2) reveal similarities between spontaneous and induced neocortical malformations and (3) fail to support a difference in behavioral effects between ectopias and microgyria.

Animals↗
PubMed1995

The neuroprotective effects of MK-801 on the induction of microgyria by freezing injury to the newborn rat neocortex.

Four-layered microgyria is associated with many developmental disorders, including mental retardation, epilepsy, and developmental dyslexia. Freezing lesions to the newborn rodent neocortex result in the formation of four-layered microgyria. Previous research had suggested this type of injury acts as an hypoxic/ischemic event to the developing cortical plate. The current study examines the effectiveness of the non-competitive N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801) in protecting against freezing injury to the newborn rat cortical plate. Three groups of rats received freezing injury to the cortical plate on the first day of life (postnatal day 1). Two groups were treated with MK-801 (1 or 2 mg/kg) 0.5 h before the lesion and 6 and 14 h after, while one group received saline injections. A fourth group received MK-801 injections, but did not have a freezing lesion. The volume of neocortical abnormality was determined for all three groups in rats killed after postnatal day 7. Treatment with the higher dose of MK-801 (3 x 2 mg/kg) dramatically reduced the effects of freezing injury but also resulted in over 50% mortality in both lesioned and unlesioned groups. Animals in the lesioned group, however, had a decreased volume of abnormal cortex, and there were fewer animals with microsulci than in the untreated group. This is the first demonstration of a significant anatomical neuroprotective effect in newborns leading to a reduction of cortical malformation.

Animals↗
PubMed1994

Radial glia in the neocortex of adult rats: effects of neonatal brain injury.

Microgyria can be induced in otherwise normal rat neocortex by a freezing injury to the cortical plate before the completion of neuronal migration. We had previously reported radial glial like-immunoreactive fibers in the area of the microgyria in 32-day-old rats. Here we demonstrate that these glial fibers, which are immunoreactive to Rat-401, vimentin, and glial fibrillary acidic protein (GFAP) antibodies, are seen in adult rats. The appearance of these fibers is hypothesized to result from the release of a trophic factor during the recovery from neonatal injury which acts to either (1) halt the transformation of radial glia to astrocytes and/or dedifferentiate already committed astrocytes, (2) create a hybrid cell, or (3) induce increased proliferation of glia.

Aging↗
PubMed1994

Evidence for aberrant auditory anatomy in developmental dyslexia.

Abnormal auditory processing in dyslexics suggests that accompanying anatomical abnormalities might be present in the auditory system. Therefore, we measured cross-sectional neuronal areas in the medial geniculate nuclei (MGNs) of five dyslexic and seven control brains. In contrast to controls, which showed no asymmetry, the left-side MGN neurons were significantly smaller than the right in the dyslexic sample. Also, as compared with controls, there were more small neurons and fewer large neurons in the left dyslexic MGN. These findings are consistent with reported behavioral findings of a left hemisphere-based phonological defect in dyslexic individuals.

Adult↗
PubMed1994

The return of Phineas Gage: clues about the brain from the skull of a famous patient.

When the landmark patient Phineas Gage died in 1861, no autopsy was performed, but his skull was later recovered. The brain lesion that caused the profound personality changes for which his case became famous has been presumed to have involved the left frontal region, but questions have been raised about the involvement of other regions and about the exact placement of the lesion within the vast frontal territory. Measurements from Gage's skull and modern neuroimaging techniques were used to reconstitute the accident and determine the probable location of the lesion. The damage involved both left and right prefrontal cortices in a pattern that, as confirmed by Gage's modern counterparts, causes a defect in rational decision making and the processing of emotion.

Accidents, Occupational↗
PubMed1994

Cytoarchitectonic anomalies in a genetically based disorder: Williams syndrome.

We report on cytoarchitectonic neocortical findings in a patient with Williams syndrome (WS), a rare genetic disorder resulting in characteristic facies, heart defect, other connective tissue anomalies, and a unique neurobehavioral profile. Cytoarchitectonic anomalies include exaggerated horizontal organization of neurons within layers, most striking in area 17; increased cell packing density throughout brain regions; abnormally clustered and oriented neurons. Overall, posterior forebrain areas were markedly diminished in volume. The results suggest that brain anomalies may relate to the extreme visuospatial deficit in WS, the dysregulation of apoptotic cell death, and the genetic basis of WS, a hemizygous deletion including the elastin locus on chromosome 7. This case provides opportunities for linking brain findings to cognitive deficits and their genetic underpinnings.

Abnormalities, Multiple↗
PubMed1993

Behavior, cortical ectopias, and autoimmunity in BXSB-Yaa and BXSB-Yaa+ mice.

The BXSB-Yaa recombinant inbred strain was created by crossing a male SB/Le with a female C57BL/6J. A Y chromosome factor derived from the SB/Le male, known as the autoimmune accelerator (Yaa), leads to an earlier onset and greater severity of autoimmune disease in males. In contrast, male BXSB mice, which lack the Yaa gene (called BXSB-Yaa+) because their Y chromosome is derived from the C57BL/6J, do not develop an autoimmune condition. To examine the influence of the Y chromosome on behavior, cortical ectopia incidence, and immune functioning, males and females of these two strains were compared. Significant strain differences (for both sexes) were found for behavioral measures including discrimination, spatial and avoidance learning, and activity. For immunological parameters, a sex difference was seen in the BXSB-Yaa (males more autoimmune), but not in the BXSB-Yaa+ strain. As expected, male BXSB-Yaas were more autoimmune than male BXSB-Yaa+s. However, there was also a strain difference for IgG in the females (BXSB-Yaa+ greater). No strain difference was found for the presence of ectopias. However, there was a sex difference across both strains, with males having a higher incidence. BXSB-Yaa and BXSB-Yaa+ mice have behavioral and immunological differences greater than would be predicted by their known genetic differences. The significant differences between the two female groups suggest that the two strains differ with respect to autosomal genes, in addition to the Y chromosome. The incidence of ectopias is independent of this genetic difference and is influenced by the subject's sex.

Animals↗
PubMed1993

Neuronal subtypes and anatomic asymmetry: changes in neuronal number and cell-packing density.

The combined volume of an asymmetric cytoarchitectonic area is smaller than that of symmetric homologs. Asymmetry reflects fewer numbers of neurons in the smaller of the two sides. In this study we examined two types of neurons to check whether lateral differences in neuronal numbers affect different types of neurons comparably in the neocortex of the rat. As with overall neuronal numbers, both parvalbumin-immunoreactive (mostly long projection) neurons, and vasoactive intestinal peptide-immunoreactive interneurons increase in number in the larger of the two sides. Moreover, the concentration of parvalbumin- but not vasoactive intestinal peptide-immunoreactive neurons also increases on the larger side. Thus, there may be qualitative as well as quantitative differences in the connectivity of the larger side of an asymmetric architectonic region.

Animals↗
PubMed1993

Neurology of developmental dyslexia.

Developmental dyslexia was until recently considered to belong solely in the domain of educational psychology. With the advent of better theories on language and reading, and better methods for assessing the structure and function of living human brains and for determining genetic transmission, dyslexia is now poised to become a focal concern of cognitive neuroscience, neurology, and genetic research. Still unresolved are questions relating to how much a reading disability represents a normal variation or a separate pathological entity, and whether the cognitive disorder is primarily cognitive, or secondary to a disorder in early perception. Recent findings from neuroanatomy, neurophysiology, neuropsychology, and genetics research are reviewed. (This review is an updated version of a review first published in Current Opinion In Neurology and Neurosurgery 1992, 5:71-76.)

Brain↗
PubMed1993

Neuroanatomic basis of developmental dyslexia.

This article reviews the known neuroanatomic and neuropathologic bases of developmental dyslexia in the context of some of the functional deficits exhibited by affected individuals. Observations from autopsy brains and experimental animal models disclose problems with cerebral asymmetry, focal developmental disorders affecting the cerebral cortex, and abnormalities in the magnocellular pathway of the visual system.

Animals↗