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R D Lund

Publications and source records attributed to R D Lund.

At least 19 recordsLinked to original sources
PubMed1992

Migration of astrocytes transplanted to the midbrain of neonatal rats.

Previous studies have indicated that transplanted astrocytes are able to survive, express glial fibrillary acidic protein (GFAP), and migrate in the host brain, and that the pattern and speed of astrocyte migration is largely determined by the location of the graft. We examine here the pattern of astrocyte migration in the midbrain by transplanting CD-1 mouse corpus callosum (P2-3) into the midbrain of neonatal rats. The location of the grafts and the distribution of donor astrocytes were assessed by using a monoclonal antibody (anti-M2) specific for mouse astrocytes. A characteristic donor astrocyte distribution was seen. The highest density of cells was in the region of the substantia nigra (SN); lower numbers were found in the medial geniculate nucleus (MGN). Donor astrocytes were also found in the superior colliculus (SC) and central gray region, but only when the body of a graft was located nearby. [3H]thymidine studies showed that the concentrations of donor astrocytes in the SN were not the result of high levels of mitotic activity: all indications were that the proportion of dividing donor cells closely matched that of host glia. The pattern of astrocyte migration in the midbrain did not follow the course established by radial glia and was not influenced by axonal degeneration in the SC after removal of eyes. Moreover, donor cells failed to migrate along the course of axonal outgrowth from co-grafted retinae. Reciprocally, axonal elongation from retinal grafts did not follow the pathway of astrocyte migration, thus suggesting that astrocyte migration and neuronal outgrowth follow different cues.

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PubMed1992

Neonatal host astrocyte migration into xenogeneic cerebral cortical grafts.

Migration of host astrocytes into grafts was investigated by transplantation of rat cortex (E16) into the cortex or midbrain of neonatal mice. Host astrocytes, visualized by the mouse astrocyte-specific antibody, began to invade the grafted cortex during the first week post-transplantation and sequentially migrated substantial distances throughout the graft. Host cells in the grafts which were undergoing immune rejection became hypertrophic. These results have important implications when assessing interactions between host and graft cells.

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PubMed1992

Long-term survival of mouse corpus callosum grafts in neonatal rat recipients, and the effect of host sensitization.

Previous studies have suggested that the incidence of spontaneous rejection among immunogenetically mismatched neural transplants in neonatal recipients varies significantly depending on the cellular composition of the graft material. For example, neuron-rich grafts of embryonic mouse retina generally survive for extended periods without showing signs of rejection after implantation into neonatal rats, whereas cortical xenografts, which contain abundant glial and endothelial cells as well as neurons, typically undergo rejection 4-6 weeks after implantation. To determine whether the presence of donor glia is responsible for this high incidence of spontaneous rejection, we examined the fate of a non-neuronal graft material composed predominantly of xenogeneic glial cells (post-natal day 3, PD3, CD-1 mouse corpus callosum) implanted into the mesencephalon of PD1 Sprague-Dawley rats. The distribution and survival of donor astrocytes were assessed using a monoclonal antibody specific for a mouse astrocyte surface antigen, M2. Thirteen of 16 animals sacrificed within 2 months of implantation had detectable transplants. In these animals, M2-positive cells frequently migrated well away from body of the graft, clustering in large numbers in several characteristic regions of the host brain. Unlike cortical grafts of similar age, the vast majority (93%) of callosal transplants showed no histological signs of rejection or major histocompatibility complex antigen expression in and around the transplant-derived cells. As previously noted in the neonatal retinal transplant paradigm, however, well-integrated 1-month-old corpus callosum grafts could be induced to reject by appropriate sensitization of the host immune system, implying that the host was not immunologically tolerant to the foreign neural graft. With longer survival times in unsensitized hosts, a progressively smaller percentage of animals had detectable donor astrocytes (5 of 10 animals at 3 months postimplantation and 4 of 16 animals at 4 months); in those 9 animals with surviving grafts, only small numbers of M2-positive cells were seen within the graft bed and surrounding host brain. However, only 2 of the 26 "long-term" animals showed evidence of graft rejection. These results indicate that mouse astrocytes show characteristic patterns of migration into the host brain when implanted into neonatal rats; however, these xenogeneic cells have a limited duration of survival. The infrequency with which even subtle signs of spontaneous rejection were detected in animals that had received corpus callosum xenografts suggests that an immune-mediated process is unlikely to be responsible for the time-dependent elimination of the donor astrocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1992

A role for microglia in the maintenance of photoreceptors in retinal transplants lacking pigment epithelium.

Studies on intact retina have pointed to a necessary role for retinal pigment epithelium in the maintenance of photoreceptor outer segments and for regeneration of visual pigment. However, it has been shown that when embryonic retinae are separated from the pigment epithelium and transplanted into the brain of neonatal rats, the transplanted photoreceptors develop outer segments and the retina responds to light in the apparent absence of pigment epithelial cells. We confirm that there are no retinal pigment epithelium cells associated with transplanted retinae in the present series of experiments and show that a row of cells, composed predominantly of microglia of host origin, border the graft. These cells can be seen to contain engulfed outer segments when they are apposed to the outer retina, suggesting that the microglia have assumed, at the least, the phagocytic function normally associated with retinal pigment epithelium. Microglial cells and their processes are also found within the transplant, but these cells are typically devoid of phagosomes, indicating an absence of phagocytic activity. The close physical association of these resting microglia with the transplant may facilitate their role in antigen presentation under specific conditions of immune provocation.

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PubMed1992

cFos labeling in rat superior colliculus: activation by normal retinal pathways and pathways from intracranial retinal transplants.

Previous studies in this laboratory have shown that intracranial retinal transplants can establish both anatomical and functional connections with the host brain. Embryonic rat retinae transplanted intracranially into neonatal host brains are capable of evoking appropriate physiological and behavioral responses when illuminated. The present study employs the specific expression of the cFos protein to identify brain regions in which immediate-early gene activation can be recognized in response to flash stimuli delivered to retinal transplants and to normal intact retinae. Stimulation of the intact eye induced significant cFos expression in various visual centers, including the stratum griseum superficiale of the superior colliculus and the pretectal area, but not in the dLGN, suprachiasmatic nucleus, or retina. Animals with functional transplants expressed cFos throughout the depth of the stratum griseum superficiale and stratum opticum of the superior colliculus, thus apparently activating an additional population of superior collicular cells. Like the eye-stimulated animals, animals with functional transplants failed to elicit significant cFos expression in the dLGN or transplanted retina. This study indicates that intracranial retinal transplants are capable of forming functional connections with the host superior colliculus which not only mediate transient changes in electrical activity but also may affect gene expression through the induction of the c-fos gene.

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PubMed1991

Rapid enhancement of transplant-mediated pupilloconstriction after elimination of competing host optic input.

Retinae transplanted over the brainstem, when directly illuminated, cause pupilloconstriction in the host eye. This occurs even when the host eye is maintained in darkness. If the host optic nerve is then severed, the transplant-mediated response is substantially augmented within 1-2 days. It is suggested that this is due to enhancement of the signal-to-noise ratio resulting from elimination of dark discharge in the host optic nerve.

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PubMed1991

Plasticity in innervation of the rat superior colliculus by transplanted retinae as a result of eye removal at maturity.

When the superior colliculus of a rat is innervated by inputs from both eyes as well as a retina transplanted intracranially over one tectum at birth, the tectal projection from the transplant is confined mainly to the superficial surface of the superior colliculus. The transplant-derived fibers possess a simple morphology, lacking terminal arborizations. If the contralateral eye is removed one month after transplantation, these fibers can be induced to arborize into the denervated portion of the superior colliculus over the next month. This demonstration of sprouting in a mature sensory relay system raises the possibility that an enhancement of behavioral responses mediated by transplanted retina might also occur. In turn, this may provide an ideal system to study the correlation between anatomical changes in transplant axons and changes in behaviors mediated by transplant activity.

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PubMed1991

The impact of intracerebral retinal transplants on types of behavior exhibited by host rats.

Retinae transplanted over the midbrain of newborn rats establish functional connections with host brain centers, which provide a substrate for several distinct visual functions. These responses provide insight into the relationship between anatomy and behavior under normal conditions and after brain injury, as well as into the strategies used by an animal to extract significant information from its visual environment.

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PubMed1990

Fetal olfactory bulb transplants send projections to host olfactory cortex in the rat.

We are using the rat olfactory system to study developmental details of neurotransplantation. Tritiated [3H]thymidine-labeled fetal olfactory bulbs (OBs), were transplanted immediately into sites from which the neonatal host OB was removed. Subsequently, a small lesion was placed in the region of the transplanted OB and the tissue studied, using degeneration methods and autoradiography. Only OB's with extensive [3H]-label and precise lesions confined to the labeled areas were used. Degeneration was found mainly in the ipsilateral piriform cortex with lesser amounts at other nearby sites. The results demonstrate successfully transplanted donor OBs that send axons to specific and appropriate target areas of the host brain.

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PubMed1990

Proximity as a factor in the innervation of host brain regions by retinal transplants.

Embryonic mouse retinae transplanted to a variety of locations within the rostral midbrain of neonatal rats exhibit selective innervation of host visual nuclei when studied at maturity. Some of these nuclei (superior colliculus, nucleus of the optic tract, dorsal terminal nucleus) usually receive extensive transplant projections, others are innervated partially (dorsal division of the lateral geniculate nucleus, olivary pretectal nucleus, medial terminal nucleus), while a few (ventral division of the lateral geniculate nucleus, suprachiasmatic nucleus, intergeniculate leaflet) are not innervated at all. The selectivity of this innervation is largely independent of the transplant's position within the rostral brainstem, while the density of innervation of individual nuclei depends in part upon the proximity of the transplant to the nucleus and upon whether the host retinal projection to that nucleus is present or absent. These findings provide a foundation for further studies of the behavioral capabilities of retinal transplants, for developmental studies of factors responsible for the establishment of normal neural projections, and for examination of the immunological consequences of transplantation.

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PubMed1990

Amphetamine sensitization of stress-induced turning in animals given unilateral dopamine transplants in infancy.

Infant rats given bilateral dopamine-depleting brain lesions and unilateral transplants of embryonic nigral tissue develop turning in response to both amphetamine and stress. However, stress-induced turning did not develop unless animals were previously exposed to amphetamine, and was greatest in animals exposed early to the drug. These findings suggest that amphetamine alters certain properties of the transplanted cells so as to enhance their functional capacity.

Amphetamines↗
PubMed1990

Directed early axonal outgrowth from retinal transplants into host rat brains.

Axons from retinae transplanted to the brain stem of neonatal rats exhibit two patterns of outgrowth that can be experimentally uncoupled from each other depending upon the location of the graft. Retinae placed close to the surface of the rostral brain stem (as much as 5 mm from the tectum) emit axons that project toward the superior colliculus along the subpial margin of the rostral brain stem. In contrast, axons from grafts embedded deep within the midbrain parenchyma project through the neuropil directly to the overlying superior colliculus, as long as the retina is within about 1 mm of the tectal surface. The present study shows that, as long as the retina is located outside the superior colliculus, and regardless of whether the axons derive from grafts in subpial or intraparenchymal locations, the earliest projections are oriented towards the superior colliculus. We have also found, however, that axons from retinae transplanted directly onto the superior colliculus can form projections that extend along the subpial margin away from the tectum. There are several major conclusions that may be drawn from these observations. First, the final tectopetal, transplant-derived projection does not result from the reorganization of an initially random outgrowth but is directed from the start toward an appropriate region of termination. Second, it appears that the interaction of retinal axons with a primary target alters the ability of the growth cone to respond to directional cues along the optic tract. Thus, although adding support to the proposal that optic axons attain the superior colliculus through an interaction involving substrates distributed along the optic tract and diffusible factors originating in the target region, it is increasingly clear that such interactions are likely to be complex and hierarchical.

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PubMed1990

The blood-brain barrier protects foreign antigens in the brain from immune attack.

To examine the role of the blood-brain barrier (BBB) in maintaining immune privilege in the brain, the BBB in the region of stably integrated mouse neural grafts implanted in neonatal rat brains was transiently disrupted by intracarotid infusion of hypertonic mannitol. This led to graft rejection and to prominent expression of major histocompatibility complex (MHC) antigens on cells adjacent to the graft. Grafts in control animals receiving an intracarotid infusion of isotonic saline showed only rare MHC expression and no increased incidence of rejection. Opening the barrier in the absence of a graft caused neither MHC expression nor cellular infiltration within the brain, suggesting that the effects of the hypertonic infusion were not produced by an indirect injury-mediated effect on the host brain. We conclude that the integrity of the blood-brain barrier is an important factor in the relative immune privilege of nonsyngeneic neural grafts.

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PubMed1979

Intertectal crossing of optic axons after tectal fusion in neonatal rats.

Surgically-induced fusion of the superior colliculi along the midline was performed in newborn rats to provide a bridge for optic axons from one eye to cross the tectal midline. The results indicate that although tectal fusion is a necessary condition of optic axons to cross from one side of the midbrain to the other, it is not sufficient by itself to induce crossing unless the optic input from the opposite side is also removed. This finding is discussed in relation to tectal lesion studies and is compared with our previous observations of the corticotectal pathway.

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