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S C McLoon

Publications and source records attributed to S C McLoon.

36 records · Page 2Linked to original sources
PubMed1988

Transient expression of laminin in the optic nerve of the developing rat.

The optic nerve of the developing rat was examined for the presence of laminin, an adhesive glycoprotein, to assess whether it might serve as a substrate for retinal axon growth in vivo. The optic stalk and nerve of developing rats were screened immunohistochemically for the presence of laminin before, during, and after the period of retinal axon growth. On embryonic day 14 (E14), laminin immunoreactivity was present in the ventral portion of the optic stalk, the same region in which the first retinal axons grow. Between E16 and postnatal day 10 (P10), cells positive for laminin were distributed throughout the cross-sectional area of the nerve. There was a progressive appearance of glial fibrillary acidic protein (GFAP) immunoreactivity, a marker for astrocytes, from the optic nerve head towards the chiasm beginning on E20. At the advancing front of GFAP immunoreactivity, cells were positive for both laminin and GFAP. Behind the front, laminin immunoreactivity disappeared from the cells. By P12, the only laminin immunoreactivity that remained within the optic nerve surrounded the vasculature. This is a time after the last retinal axons grow through the optic nerve. Monolayer cell cultures were prepared from perinatal rat optic nerves and processed for immunohistochemistry to determine which astrocyte type was laminin-positive. Type 1 astrocytes, which primarily compose the immature nerve, are GFAP-positive, A2B5-negative, and laminin-positive. Type 2 astrocytes, a major component of the mature optic nerve, were GFAP-positive, A2B5-positive and laminin-negative. An extract of developing optic nerve was analyzed by immunoblot along with laminin purified from Engelbreth-Holm-Swarm (EHS) sarcoma. Purified laminin ran with SDS-PAGE under reducing conditions as 2 bands with Mrs of 200,000 and 4000,000. Both bands reacted with antibodies to laminin. A low-salt extraction of whole optic nerve from E18 rats resulted in 2 bands with the same Mr as seen with laminin from EHS sarcoma. When only the inside of the optic nerve (which lacked the basal lamina and meninges that surround the outside) was processed, there was a dark 200,000 D band, but the 400,000 D band was virtually absent. These results are consistent with the hypothesis that laminin, or a variant form of laminin, serves as a substrate for retinal axon growth in the developing rat optic nerve.

Animals↗
PubMed1986

Distribution of laminin in the developing peripheral nervous system of the chick.

During axonal elongation in the developing peripheral nervous system, the temporal and spatial distribution of adhesive molecules in extracellular matrices and on neighboring cell surfaces may provide "choices" of pathways for growth cone migration. The extracellular matrix glycoprotein laminin appears in early embryos and mediates neuronal adhesion and neurite extension in vitro. In this study, we have examined the distribution of laminin at early periods of peripheral nervous system development. The distribution of laminin, demonstrated by immunostaining frozen sections of chick embryos, was compared to the distribution of fibronectin and of early peripheral neurites as revealed with an antibody to a neurofilament-associated protein. Laminin is present in the neural tube basement membrane, in early ganglia, and in developing dorsal and ventral roots, where the laminin staining pattern parallels that of neurofilaments. In early ganglia and nerve roots, laminin immunostaining defines loose "meshworks" rather than basement membranes, which seem to form slightly later in these structures. In contrast, fibronectin is absent in neural tube basement membrane, ganglia, and nerve roots, although it is present along neural crest migratory pathways and in intersomitic spaces. Our observations of laminin distribution are consistent with the possibility that laminin provides an adhesive surface for neurite extension at some stages of early peripheral nervous system development.

Age Factors↗
PubMed1986

Response of astrocytes in the visual system to Wallerian degeneration: an immunohistochemical analysis of laminin and glial fibrillary acidic protein (GFAP).

Eye removal in adult rats resulted in an increase in immunohistochemical staining with antibodies to glial fibrillary acidic protein in the optic nerve, optic tract, and primary visual nuclei. Astrocytes along the primary visual pathway did not stain with antibodies to laminin in response to eye removal. There was an increase in laminin immunoreactivity associated with blood vessels along the injured pathway. These blood vessels were also shown to have an increased size. The lack of laminin induction in astrocytes along the path of degenerating optic axons may be responsible in part for the inability of axons to regenerate in the primary visual system.

Animals↗
PubMed1986

The appearance of an L1-like molecule in the chick primary visual pathway.

A monoclonal antibody, 8D9, has been obtained that binds to axons in the chick nervous system. Biochemical and immunological experiments indicate that the 8D9 antigen is related to the mouse L1 cell-adhesion molecule. The results of immunohistochemical experiments using monoclonal antibody 8D9 to study the development of the chick visual system are consistent with the 8D9 antigen functioning in axon fasciculation.

Animals↗
PubMed1985

Ganglion cells in retinae transplanted to newborn rats.

Cells projecting out of retinal transplants placed over the tectum of newborn rats were studied by labelling with horseradish peroxidase 1 month or more after transplantation. Using this technique, it was found that only cells with the dendritic characteristics of ganglion cells were labelled and, furthermore, that the major classes of ganglion cells seen in normal retinae were also present in the transplants. The cell body size histograms of ganglion cells in normal and transplanted retinae compared closely with each other. Dendritic trees were closely confined by the limits of the inner plexiform layer, and if that layer was folded or distorted, they were themselves frequently abnormal. While axons usually coursed over the surface of the retinal transplants, they quite often followed an anomalous course crossing the individual layers. It appears, therefore, that this transplantation procedure has relatively little impact on the ability of ganglion cells to develop many of their characteristic morphological features. Whether the different functional responses of the various ganglion cell classes are also preserved after transplantation is a matter for further investigation.

Animals↗
PubMed1985

Evidence for shifting connections during development of the chick retinotectal projection.

The pattern in which optic axons invade the tectum and begin synaptogenesis was studied in the chick. The anterogradely transported marker, horseradish peroxidase, was injected into one eye of embryos between 5 and 16 days of development (E5 to E16). This labeled the optic axons in the brain. The first retinal axons arrived in the most superficial lamina of the tectum on E6. They entered the tectum at the rostroventral margin. During the next 6 days of development the axons grew over the tectal surface. First they filled the rostral tectum, the oldest portion of the tectum, and then they spread to the caudal pole. Shortly after the first axons entered the tectum on E6, labeled retinal axons were found penetrating from the surface into deeper tectal layers. In any given area of the tectum, optic axons were seen penetrating deeper layers shortly after arriving in that area. Electron microscopic examination showed that at least some of the labeled axons in rostral tectum formed synapses with tectal cells by E7. These results show two things which contrast with results from previous studies. First, there is no delay between the time the retinal axons enter the tectum and the time they penetrate into synaptic layers of the tectum. Second, the first retinotectal connections are formed in rostral tectum and not central tectum. Retrograde tracing showed the first optic axons that arrived in the tectum were from ganglion cells in central retina. Previous studies have shown that the ganglion cells of central retina project to the central tectum in the mature chick. This opens the possibility that the optic axons from central retina, which connect to rostral tectum in the young embryo, shift their connections to central tectum during subsequent development. As they enter the tectum the growth cones of retinal axons appear to be associated with the external limiting membrane. During the time that connections would begin to shift in the tectum a second population of axons appears at the bottom of stratum opticum, some with characteristics of growth cones. This late-appearing population may represent axons shifting their connections. These results have implications for theories on how the retinotopic pattern of retinotectal connections develops.

Animals↗
PubMed1984

Loss of ganglion cells in fetal retina transplanted to rat cortex.

Fetal retina survived and differentiated when placed into the cortex of newborn host rats. Two months after transplantation, anterograde tract tracing techniques failed to reveal any projections from these transplants into the host brain. Soma-size analysis of the cells in the ganglion cell layer of the transplants suggested that only displaced amacrine cells remained and that the ganglion cells had degenerated. The basis for these results is considered relative to trophic maintenance of ganglion cells, retinal axon guidance, and specificity of connections.

Animals↗
PubMed1983

Development of fetal retina, tectum, and cortex transplanted to the superior colliculus of adult rats.

Earlier studies showed that embryonic retina, cortex, or tectum transplanted adjacent to the superior colliculus of newborn host rats differentiated many of the histological features appropriate for the donor region and developed interconnections with the host nervous system. In the study presented here, the same regions were transplanted to the brain of adult host rats and the development of these transplants was compared to those into newborn hosts. Retina, rostral tectum, or occipital cortex was dissected from donor rat embryos on gestational day 14 or 15. A portion of cortex was aspirated in 2-month-old host rats to expose the right superior colliculus, and one of the donor tissues was placed adjacent to the colliculus in each host. Two to 4 months after transplantation, transplant histology and neuronal interconnections between the transplant and host nervous system were studied by using Nissl and neurofibrillar stains and 3H-proline and HRP tract tracing techniques. Four main points can be drawn from these results. First, 80% of the transplants survived in adult hosts - a percentage comparable to that found in newborn hosts. Second, each of the types of tissues transplanted differentiated histological characteristics appropriate for its site or origin, although the degree of differentiation was always much less than in transplants to newborns. Third, the transplants developed only relatively local projections into the host cortex and superior colliculus. This contrasts with the extensive projections found from the transplants into the brain of newborn hosts. Fourth, no definitive projections from the host retina or brain were identified to any of the transplants into adults, whereas both cortical and tectal transplants into newborns received projections from the host.

Age Factors↗
PubMed1982

Alterations in precision of the crossed retinotectal projection during chick development.

Chick embryos received partial eye lesions. Examination of the embryos early in development showed the partial retina projecting across the entire tectum. At later stages the partial retina projected only to the appropriate portion of the tectum. The results suggest that the retina initially projects diffusely to the tectum and that the topographically aberrant projections are eliminated during subsequent development.

Animals↗
PubMed1982

Transplantation of reaggregates of embryonic neural retinae to neonatal rat brain: differentiation and formation of connections.

Embryonic day 14 neural retinae were dissociated into single cells and reaggregated prior to transplantation over the superior colliculi of newborn rats. One month after transplantation, the brains of the host rats were examined for transplant differentiation and the formation of projections from the transplant to the host brain. All reaggregated retinal transplants differentiated in the host brain, showing normal lamination and cellular morphology. Electron microscopic examination demonstrated normal synaptology with the transplanted retinal neuropil. Horseradish peroxidase injections into the host superior colliculus retrogradely filled cells within the transplant. These cells were found in the lamina corresponding to the ganglion cell layer and displayed a morphology characteristic of normal ganglion cells. Lesions of the transplants confirmed the projection of the reaggregated retinal transplants to superior colliculus. Degeneration was also traced into a number of ther nuclei that are normally retinorecipient. The presence of degenerating synaptic terminals resembling those seen after eye removal in control rats was confirmed by electron microscopic examination. It appears that despite disruption of initial cell-cell associations early in retinal development and prior to transplantation, the reaggregated transplants retain the ability to differentiate and form appropriate connection with the host brain.

Animals↗
PubMed1982

Transient retinofugal pathways in the developing chick.

The central retinal projections have been examined in normal chick embryos early in development to determine if a transient ipsilateral projection is present. Anterograde transport of HRP identified using tetramethyl benzidine as a chromogen and degeneration techniques were used on embryos of successive ages between 6 and 16 days of incubation to show the central distribution of the retinal axons from one eye. Besides the anticipated contralateral projection, a small projection was identified to primary visual nuclei on the side of the brain ipsilateral to the injected or lesioned eye in embryos between days 6 and 12 of incubation. A projection from the injected eye into the contralateral optic nerve was also identified in a number of embryos. By embryonic day 15 the retinal projection to the ipsilateral side of the brain and into the contralateral optic nerve had disappeared. This loss of the anomalous projections coincides with a period of substantial cell death in the retinal ganglion cell layer. It appears, therefore, that in the chick, like the rat, the ipsilateral retinofugal projection resulting from an embryonic enucleation may in part be due to retention of a normal ipsilateral projection.

Afferent Pathways↗
PubMed1981

Cultured embryonic retinae transplanted to rat brain: differentiation and formation of projections to host superior colliculus.

Retinae of rats on embryonic day 14 were placed in explant culture for 2-14 days prior to transplantation adjacent to the superior colliculus of newborn rats. In explant culture cell division and neuronal differentiation continued unabated. One month after transplantation host brains were examined for transplant survival, differentiation and formation of projections to the host brain. The cultured retinal transplants survived and developed a morphology typical of mature retina, with normal cell and fiber laminae present. HRP injections into the host superior colliculus labeled neurons in the ganglion cell layer of the transplant which closely resembled ganglion cells in vivo. A small number of transplants received lesions. Degeneration material was traced into the superior colliculus and pretectal nuclei confirming that the cultured transplants had projections appropriate for retina entering the host brain. These results correlate closely with those seen after transplantation of embryonic rat retinae that had not been cultured. Thus, a period of explant culture of up to two weeks does not affect the ability of embryonic retinal transplants to differentiate and form projections into the host brain.

Animals↗
PubMed1980

Specific projections of retina transplanted to rat brain.

Retinae were taken from fetal rats and transplanted adjacent to the superior colliculus of neonatal rats. After 1 month survival, the transplants were surgically removed from the hosts, locally damaged or injected with horseradish peroxidase (HRP) to determine the distribution of the transplant efferents in the host brains. Histological examination of the transplants revealed cell and plexiform layers characteristic of normal retinae. Since the retinae were undifferentiated at the time of transplantation, this layering developed within the host. The only obvious differences from normal retina were that the layers were organized in rosettes or folded sheets and lacked well developed photoreceptor outer segments. In animals which had lesions or HRP injections confined to the retinal transplant, proper staining of sections of the host brain revealed transplant projections. These projections were confined to the optic tract and nuclei which are normally retinorecipient such as the superior colliculus and dorsal lateral geniculate nucleus. Projections were found along the border of non-retinorecipient nuclei such as the lateral posterior nucleus, but did not appear to enter these nuclei. It was observed that within the superior colliculus the host retinal input had an effect on the distribution of the transplant projection. In one-eyed hosts the transplant projection was distributed throughout the stratum (s.) zonale, s. griseum superficiale, and s. opticum; whereas in the two-eyed hosts, the transplant projection was confined to the s. zonale and the border between x. griseum superficiale and s. opticum. We suggest that a special affinity exists between the axons of the retinal transplants and host visual structures. Furthermore, factors, such as competition and timing may be important in determining the distribution of the transplant axons within the specific target nuclei. Transplantation appears to be a useful technique for further studies on the mechanisms underlying the development of specific neuronal connections.

Animals↗
PubMedDate not supplied

Antinociception following implantation of AtT-20 and genetically modified AtT-20/hENK cells in rat spinal cord.

AtT-20 cells, which produce beta-endorphin, and AtT-20/hENK cells, which are AtT-20 cells transfected with a proenkephalin gene, were implanted in the rat spinal subarachnoid space in an effort to produce an antinociceptive effect. Host rats were tested for antinociceptive activity by standard nociceptive tests, tail flick and hot plate. Although cell implants had minimal effect on the basal response to thermal nociceptive stimuli, administration of the beta 2-adrenergic agonist isoproterenol produced antinociception in the cell-implanted group but not in the control group. The antinociceptive effect of isoproterenol was dose-related and could be blocked by the opioid antagonist naloxone. Immunohistochemical analysis of spinal cords revealed the presence of enkephalin-negative cells surrounding the spinal cord of rats receiving AtT-20 cell implants, and enkephalin-positive cells surrounding the spinal cord of rats receiving AtT-20/hENK cell implants. These results suggest that opioid-releasing cells implanted around rat spinal cord can produce antinociception and may provide an alternative therapy for chronic pain.

Animals↗