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G Raisman

Publications and source records attributed to G Raisman.

At least 55 records · Page 3Linked to original sources
PubMed1993

Monoclonal antibody G10 which recognises microtubule-associated protein 1x identifies growing axons of neurons microtransplanted into adult rat hippocampus.

Monoclonal antibody G10 recognises an epitope on microtubule-associated protein 1x, a developmentally regulated cytoskeletal protein expressed in immature axons of the central and peripheral nervous systems. Here we report that G10 can be used to identify the axonal projections of syngeneic embryonic (E14-E15) hippocampal cells microtransplanted by a minimally traumatic technique into intact adult host hippocampus.

Animals↗
PubMed1993

Rapid decline in the ability of entorhinal axons to innervate the dentate gyrus with increasing time in organotypic co-culture.

We have used the species-specific monoclonal antibodies OM1 and OM4 to identify the histiotypic pattern of projection from late embryonic rat entorhinal explants to the outer molecular layer of the dentate gyrus in organotypic cultures of 6-day postnatal mouse hippocampal slices. The presence of this entorhinal projection was detectable with the rat-specific OM1 and OM4 markers after 3-7 days in co-culture, and confirmed by use of the later-forming rat neuron-specific marker THy-1.1, which appeared during the second week. Hippocampal slices confronted with control explants of superior colliculus for 4 weeks in culture showed only sparse, non-specific growth of axons with no histiotypic pattern in the dentate gyrus. In order to assess whether the formation of specific entorhino-dentate projections in vitro is age-dependent, embryonic rat entorhinal cortical explants were cultured alone for periods of 1-5 weeks before cutting across the halo of axons radiating into the collagen matrix and presenting each with 6-day-old mouse hippocampal slices as targets to innervate. After allowing a 2 week period for fibre growth to take place, the density of immunostained axonal outgrowth was scored on a five-point scale for each weekly interval. The amount of new axon growth when the cuts were made after 1 week was slightly reduced compared to undamaged control cultures. However, outgrowth was greatly diminished when the cuts were made after 2 or 3 weeks, and essentially abolished if the interval was extended to > or = 4 weeks. Thus we demonstrate that, although hippocampal slices can survive in organotypic co-culture with entorhinal explants and maintain previously formed connections, the explants show an age-related failure in the ability to form new connections. Such a system provides a possible in vitro model for study of the factors influencing the failure of regeneration in the adult central nervous system.

Animals↗
PubMed1993

Long axon growth from embryonic neurons transplanted into myelinated tracts of the adult rat spinal cord.

Suspensions of embryonic mouse hippocampal neurons were micro-transplanted into the high cervical region of the corticospinal tracts and the ascending dorsal columns of immunosuppressed adult rat hosts. The mouse specific marker, M6, showed that the transplanted neurons grew long, straight, and uniform axons which passed both rostrally and caudally in a narrow beam within the tract occupied by the transplant. The donor axons did not fasciculate with each other, but were intermingled singly with the host myelinated axons, parallel to them and to the host interfascicular glial rows. The donor axons extended at about 0.5 mm per day for the first 6-10 days, after which they slowed down, gradually reaching a maximum distance of around 8 mm from the grafts by 6-7 weeks. Beyond this time M6 ceased to be an effective marker. The presence of the donor axonal projections was confirmed by retrograde cellular labelling of the donor cells from injections of horseradish peroxidase caudal to the transplants in the same host tract. To test whether the donor embryonic hippocampal axons would be attracted to neuropil containing appropriate postsynaptic sites, embryonic rat hippocampal grafts were placed caudal to the mouse grafts. When placed where they could make direct contact with the projection, the rat grafts became M6 positive, suggesting that they had been innervated by mouse axons. But even when placed directly within the beam of donor projections, the rat grafts did not prevent large numbers of mouse axons from continuing caudally in the host spinal tracts. When the rat grafts were placed to one side of the beam of donor projection, the long projecting mouse axons did not deviate from their course. Thus the long ascending and descending myelinated fibre tracts of the adult spinal cord provide a permissive environment for the rapid growth of axons from embryonic donor neurons from a region not normally projecting to the spinal cord. The route taken by these axons is determined by the internal structure of the host tracts. Donor interfascicular axons are able to pass, without deviation, through or beside tissue containing appropriately matched postsynaptic targets.

Animals↗
PubMed1993

Long fibre growth by axons of embryonic mouse hippocampal neurons microtransplanted into the adult rat fimbria.

We have described a method for the microtransplantation of a suspension of a few thousand cells from mid to late embryonic mouse hippocampi into the fimbria of immunosuppressed adult rat hosts. There was close graft-to-host contact, across a non-scarred interface. The transplanted cells included CA3 type pyramids, and were enclosed within the host myelinated fibre tract, whose glial framework was largely undisturbed. Immunohistochemistry of two species-specific markers (M6 and Thy-1.2) showed that the donor mouse neurons grew fine (< 0.5 micron diameter) axons which extended singly or in fascicles through the rat host fimbria for a maximum distance of at least 10 mm. The donor axons were intimately integrated among and closely aligned to the host tract axons and to the interfascicular glial rows of the host tract. The axons travelled (i) laterally through the ipsilateral fimbria, (ii) medially across the midline in the ventral hippocampal commissure to reach the contralateral fimbria and alveus, and (iii) rostro-medially to the septum. On approaching the terminal fields appropriate to hippocampal CA3 pyramidal cell axons, the transplant axons gave rise to fine preterminal branches which were continuous with a reticular or amorphous immunoreactivity in the stratum oriens and stratum pyramidale of the ipsilateral hippocampus, and in the lateral and triangular septal nuclei. The donor axons extended along the host fimbria at a rate of approximately 1 mm per day, reaching their terminal field destinations by approximately 1-2 weeks. At 7 weeks the projections were maintained, but with little further extension. These observations indicate that the microenvironment of myelinated adult fibre tracts is permissive for an abundant and rapid growth of axons from transplanted embryonic cell suspensions. These axons can leave host tracts to invade appropriate terminal fields.

Animals↗
PubMed1993

Morphology and migration of cultured Schwann cells transplanted into the fimbria and hippocampus in adult rats.

Schwann cells cultured from neonatal rat peripheral nerve were injected into the fimbria and hippocampus of syngeneic adult rats by a microtransplantation technique which causes minimal disturbance to the host brain structure at the site of implantation, and thus allows the grafted cells to come into immediate contact with intact host tissue. Numerous Schwann cells could be identified for up to 6 weeks (and with decreasing frequency for up to 3 months) by intense immunoreactivity for low affinity nerve growth factor receptor. The transplanted cells adopted a distinctive elongated form, with a central, ovoid nucleus flanked by processes which were up to 300 microns long, and which ranged from swollen segments with a diameter as large as 12 microns down to thread-like fibres of 1 micron or less. This morphology is different from that of any of the host cells. The transplanted Schwann cells migrated freely into the host tissue along blood vessels and according to the position of the grafts, they either entered the hippocampal neuropil, or migrated (for distances of up to 2 mm) along the longitudinal axis of the fimbria, where they were interspersed in parallel with the interfascicular glial rows and axons. The host astrocytes did not appear to impede the migration of the donor Schwann cells. Although the host astrocytic processes became hypertrophic, with increased glial fibrillary acidic protein and vimentin expression, the predominant longitudinal orientation of the astrocytic tract processes was maintained. The transplanted Schwann cells did not form peripheral myelin (as detected by P0 immunoreactivity), and it is not clear whether they survive beyond the period at which we detect them.

Animals↗
PubMed1993

Entorhinal axons project to dentate gyrus in organotypic slice co-culture.

We have demonstrated the formation of entorhinodentate projections by axons arising from explants of embryonic mouse entorhinal cortex or slices of postnatal rat entorhinal area co-cultured in contact with slices of postnatal rat hippocampus in roller tube and static culture. Species-specific markers (Thy-1 alleles and M6) showed that the most dense part of the projection was to the outer part of the molecular layer of the dentate gyrus (i.e. excluding the commissural-association zone). Retrograde axonal transport of fluorescent tracers placed in the dentate gyrus labelled a densely packed superficial layer of stellate cells in the entorhinal cortex. Anterograde axonal transport of biocytin placed in the entorhinal cortex showed that the entorhinodentate fibres formed typical parallel bundles oriented at right angles to the dentate granule cell dendrites and had short-stalked boutons. The formation of entorhinodentate synapses was confirmed in the electron microscope by electron-dense degeneration after cutting the previously formed connection between the co-cultures. Synaptic transmission was demonstrated by extracellular recording of postsynaptic field potentials after entorhinal stimulation. The entorhinal fibres also projected to the hippocampal stratum lacunosum-moleculare of fields CA1 and CA3, and were present in the outer part of the stratum oriens of the subiculum; in some cases they perforated the pyramidal cell layer of the subiculum. We conclude that the necessary molecular and tissue organizational signals for the formation of an entorhinodentate projection are present in tissues maintained in organotypic slice co-culture, and remain effective in the cross-species mouse-to-rat situation.

Animals↗
PubMed1993

Schwann cells transplanted into the CNS.

A small volume of purified Schwann cells, cultured from early postnatal rat sciatic nerve, was injected into the hippocampus or fimbria of syngeneic adult hosts. The procedure caused minimal structural disturbance at the transplantation site, with close graft-host contact and maximal opportunity for integration. The donor Schwann cells were identified by a combination of light and electron microscopic features (which include characteristic deep and complex infoldings of a well marked nuclear envelope), antigenic profile (especially low affinity nerve growth factor receptor immunoreactivity), uptake of fluorescent latex microspheres and autoradiography of [3H]thymidine-labelled dividing cells. The donor Schwann cells adopted a distinctive elongated form, with a central, ovoid nucleus flanked by processes which were up to 300 microns long, and which ranged from swollen segments with a diameter as large as 12 microns down to thread-like fibres of 1 microns or less with growth cone-like expansions. Transplanted cells migrated from the graft, particularly along blood vessels and could permeate all cytoarchitectonic regions of the adjacent host hippocampal neuropil. Donor Schwann cells also migrated along the longitudinal axis of the fimbria, where they were interspersed in parallel with the interfascicular glial rows and axons. The grafted cells induced a transient but marked host astrocytic hypertrophy, which did not appear to impede the migration of the donor Schwann cells. The transplanted Schwann cells did not form peripheral myelin (as detected by P0 immunoreactivity), and it is not clear whether they survive beyond the period at which we detect them.

Animals↗
PubMed1992

The glial framework of central white matter tracts: segmented rows of contiguous interfascicular oligodendrocytes and solitary astrocytes give rise to a continuous meshwork of transverse and longitudinal processes in the adult rat fimbria.

The cellular skeleton of the adult rat fimbria consists of regularly spaced interfascicular glial rows of considerable length, running in the longitudinal (axonal) axis of the tract. Each row consists of a series of repeated segments made up of a stretch of interfascicular oligodendrocytes lying in direct contact with each other, and separated from the adjacent segments by usually solitary interfascicular astrocytes. A typical segment would be around 60 microns long, and have an axial core of about eight contiguous oligodendrocytes surrounded by a shell of about 1,200 axons, 70% of which are myelinated. In the transverse plane of the tract, adjacent segments are stacked together with a core-to-core distance of around 15 microns. The interfascicular oligodendrocytes have radial stem processes (in a plane transverse to the axonal axis) which give rise to the longitudinal myelinating (internodal) processes. Both transverse and longitudinal oligodendrocytic processes are longer than the dimensions of the segment (in which their cell bodies lie) and its axonal shell. They thus cooperate in myelinating axons of adjacent segments in both planes. The interfascicular astrocytes have three distinct types of processes: radial, longitudinal, and vascular (bearing end feet). The radial astrocytic processes are thick and tapering, and the processes of individual astrocytes extend transversely (in the plane of the original embryonic radial glial processes) for a total of at least 100 microns. The considerably more numerous longitudinal astrocytic processes arise from all parts of the cell bodies and radial processes. They are up to at least 30 microns long, thin, untapering, and largely unbranched, and are interdigitated among the fimbrial axons. In the radial plane, the astrocytic radial processes spread out through a wide swathe of adjacent segments, so that the integrated meshwork of interpenetrating longitudinal processes arising from overlapping radial processes of astrocytes from many different interfascicular rows provides a continuous longitudinal substrate for the fimbrial axons.

Animals↗
PubMed1992

The OM series of terminal field-specific monoclonal antibodies demonstrate reinnervation of the adult rat dentate gyrus by embryonic entorhinal transplants.

Monoclonal antibodies OM-1 to OM-4 and IM-1 [Woodhams et al. (1991) Neuroscience 46, 57-69] have complementary immunostaining patterns in the molecular (dendritic) layer of the adult rat dentate gyrus, with OM-1 to OM-4 selectively recognizing the outer (distal) two-thirds (i.e. the entorhinal afferent zone), and IM-1 the inner (proximal) one-third (i.e. the hippocampal commissural/associational zone). Immunoblotting suggests that OM-1 recognizes a single glycoprotein antigen of mol. wt around 93,000, and OM-2, OM-3, and OM-4 all recognize a second glycoprotein antigen of mol. wt around 36,000. At four weeks after removal of the ipsilateral entorhinal cortex the background OM immunostaining of the entorhinal afferent zone is abolished and replaced by a network of densely stained granules, which we interpret as degenerating entorhinal afferent axons. At the same time, the proximal, IM immunoreactive zone expands by about 10 microns in width (while the distal deafferented zone shrinks by about 80 microns). Attempts were made to restore the OM immunoreactivity of the distal zone by grafting either small pieces or cell suspensions of embryonic day 18 entorhinal cortex directly into the dentate molecular layer of entorhinally deafferented adult hosts. About half (14/26) of the animals with successfully positioned grafts showed restoration of OM-2 to OM-4 immunostaining throughout the entire width of the outer two-thirds (entorhinal afferent zone) of the dentate molecular layer. Strikingly, however, in adjacent serial sections the restoration of OM-1 immunoreactivity was restricted to the "middle" molecular layer, i.e. the most proximal part of the distal (entorhinal) two-thirds of the dentate molecular layer. In no case did the OM-1 immunoreactivity extend to the outer margin of the molecular layer. This did not appear to be associated with incompleteness of the removal of the host entorhinal projection, since it occurred in grafted cases where the hippocampus had been completely isolated from the entorhinal area. The simplest explanation of the observed pattern of OM loss and restitution is that the epitopes are located on the entorhinodentate axons, but it is not clear whether the antigens recognized by OM-1 and OM-2 to OM-4 are expressed in different parts of the same group of axons, or in different subsets of entorhinodentate axons. Nor is it clear why the pattern of OM-1 is only restored to the "middle" molecular layer, while that of OM-2 to OM-4 is restored to the entire outer two-thirds.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Cultured epithelioid astrocytes migrate after transplantation into the adult rat brain.

A highly purified population of dividing epithelioid astrocytes has been prepared from postnatal rat corpus callosum. These cells were labelled in culture by incorporation of either [3H]thymidine or fluorescent microspheres and transplanted in a fibrin clot into the hippocampi of adult syngeneic rats. Transplanted cells divided in vivo and progressively migrated into the host brain from the site of implantation up to distances of about 1 mm. After a 1-week survival, transplant cells stained strongly for glial fibrillary acidic protein and had the thick sinuous processes characteristic of stellate astrocytes. Artefactual transfer of radiolabel to host cells was ruled out by control experiments in which either the proportion of transplant cells that were radiolabelled was varied or radiolabelled transplant cells were killed prior to implantation. Astrocyte migration over the first days after implantation was determined to occur at a rate of approximately 100 microns per day. Transplant cells moved into both grey and white matter areas of the host brain and over the migratory period were commonly observed to be associated with blood vessels. Some transplant cells were directly juxtaposed against neuronal perikarya and dendrites. Many labelled astrocytes were located in areas that were apparently completely free of damage caused by implantation. These results define a class of mature astrocytic cells that have the ability to migrate through the adult brain. The existence of pathways for cell movement in the adult CNS has implications for the mechanisms of tissue remodelling after injury and transplantation, for regenerative repair of the CNS, and for the dynamics of cell-cell contacts in the normal adult mammalian brain.

Animals↗
PubMed1991

Transplantation of postnatal rat enteric ganglia into denervated adult rat hippocampus.

These experiments explore the possible value of the myenteric plexus as a source of donor cells for autografting into the central nervous system. Neurons and glia from 10-12-day postnatal rat myenteric plexus survive for at least one month after transplantation into cholinergically denervated syngeneic adult rat hippocampus. A population of donor cholinergic neurons has acetylcholinesterase-positive processes, but these appear not to innervate host tissue. Host gliosis in response to these implants seems to be less than that seen with other peripheral ganglia, and unlike Schwann cells, the enteric glia form end-feet on brain capillaries.

Acetylcholinesterase↗
PubMed1991

Selective innervation of embryonic hippocampal transplants by adult host dentate granule cell axons.

Fragments containing different cytoarchitectonic fields were dissected out of late embryonic rat hippocampal primordia and transplanted into the hippocampus or septum of adult syngeneic hosts. Field CA3 transplants contained clusters of large, angular (pyramidal) cell bodies surrounded by a radiating corona of dendrites. These cells stained selectively with our monoclonal antibody Py, and a proportion were labelled by [3H]thymidine administered on the 15th day of embryonic life. Field CA1 transplants contained smaller, angular, Py-negative cells, which formed elongated laminae rather than globular clusters. The ability of the host dentate granule cells to project to the transplants was examined by (1) the Timm stain for mossy fibres, (2) electron microscopy of Golgi-impregnated CA3 pyramidal neurons in the transplants, and (3) quantitative electron microscopic assessment of the proportions of large mossy fibre terminals in the synaptic population of the transplants. The Timm stain showed that CA3 transplants received a projection from host dentate granule cells when the transplants were placed in direct contact with the axons in the host mossy fibre pathway. As in the normal host field CA3, the ingrowing mossy fibres terminated selectively on the juxtacellular regions of the dendritic tree and ignored the major part of the dendrites in the radiating corona. The electron micrographs showed that within this territory the host mossy fibres formed synaptic terminals with all the complex features typical of normal mossy fibres, and were presynaptic to complex spines arising from the juxtacellular region of Golgi-impregnated donor CA3 pyramidal cells. The quantitative electron microscopic study demonstrated that the mossy fibre-innervated juxtacellular regions of the field CA3 transplants had up to 20% of the normal density of mossy fibre synapses found in the stratum lucidum of field CA3 in situ. CA3 transplants which were placed in the septum, remote from the host mossy fibres, had either trivial numbers of mossy fibre synapses or none. This confirmed that the abundant mossy fibre terminals in the intrahippocampal CA3 transplants were of host origin, and not due to donor dentate granule cells inadvertently included in the grafts. The selectivity of the host dentate projection for field CA3 transplants was demonstrated by the observation that CA1 transplants in the same locations received only slight mossy fibre projections in the Timm stain, and in electron micrographs their synaptic population had only insignificant numbers of large mossy fibre terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Mechanisms of allograft rejection in the rat brain.

Embryonic rat hippocampal primordia from class I and class II major histoincompatible donors were transplanted into the hippocampus of adult rat hosts. The allografts were rejected by a specific host immune response, which was identified by reference to events at a histocompatible hippocampal primordial graft (syngeneic to the host) of similar embryonic age placed simultaneously in the contralateral hippocampus of the same hosts. The present combined light immunohistochemical and electron microscopic study was undertaken to elucidate the mechanism of induction of the immune response by a graft of a tissue which does not constitutively express major histocompatibility antigens, to identify which cells are involved, and how they enter the brain and attack the graft, and to look for possible sources of variability in the outcome of such an attack. Our main findings are (1) that host and graft microglia play a prominent role from the earliest stages, and throughout the evolution of the histological changes, (2) that the later entry of host dendritic cells, lymphocytes, and lymphoblasts (with associated mitoses) into the perivascular cuffs of the graft vasculature ensures that the local immune response becomes self-propagating, (3) that the allografted neurons are killed by host cytotoxic lymphocytes only after a previous encirclement by host macrophage-derived microglial cells, and (4) that the observed variability (especially within different regions of a single allograft) is associated not with failure of immune induction, but with local failure of the graft tissues to express allotypic major histocompatibility antigens. Our observations confirm that once the host immune system has been primed, local factors leading to the induction of transplant major histocompatibility complex antigens make histoincompatible intracerebral transplants of embryonic into adult brain tissue vulnerable to vigorous and effective immune attack. The histological picture of the immune response observed in our intracerebral allografts resembles that described in intraventricular allografts of embryonic brain, in allografts of other organs and tissues such as skin, kidney, and heart, and also that seen in the response to brain autoantigens in multiple sclerosis and experimental allergic encephalomyelitis. However, the involvement of a special cell type, the perivascular microglial cell, in the early stages of immune induction in brain raises the possibility of designing future therapeutic approaches which might selectively block this step in conditions such as multiple sclerosis.

Animals↗
PubMed1990

Accurate reconstruction of three complementary laminar afferents to the adult hippocampus by embryonic neural grafts.

The hippocampus receives a complex pattern of afferent nerve fibres, segregated in such a way that the different types of afferent axons terminate in strictly demarcated, contiguous, but non-overlapping territories at different proximo-distal levels on the dendrites. In this paper we have used a mouse allelic marking system to show that the dentate, hippocampal, and entorhinal afferents can all be restored correctly and specifically to their proper terminal territories by axonal projections formed by embryonic transplants placed in direct contact with the appropriate denervated terminal territories in adult host brains, and that incorrect connections are not formed. We conclude that the signals for correct reinnervation are present (or inducible by deafferentation) in the adult hippocampus. The embryo-to-adult transplantation experiments show that neither the temporal nor the spatial aspects of cell-to-cell confrontation which occur in normal development are necessary for the formation of specific laminar patterns of reinnervation in the adult.

Afferent Pathways↗
PubMed1990

Synapse formation in the adult brain after lesions and after transplantation of embryonic tissue.

Some years ago it was demonstrated that when the adult rat septal nuclei are partially deafferented the remaining afferent fibres form new connections. The conclusion that new synaptic connections form in the adult central nervous system (CNS) was greeted initially with much scepticism, later with over-enthusiasm and unwarranted generalisation to all lesion situations, together with even less warranted attribution of various beneficial functional properties. Today, as the pendulum swings into a more reasonable position, some of the original observations, which at the time attracted little attention, have become more interesting. (1) The observation that in the normal septal nuclei the ratio of spine to shaft synapses is extraordinarily constant (to an accuracy better than 1%) from one animal to another. How could such almost crystalline rigidity of structure be produced in normal development and maintained in the face of major lesion-induced changes in connectivity? (2) The observation that synaptic re-occupation by sprouting axons restores exactly the normal number of synapses, presumably indicating that the neurones have a fixed number (as well as spine/shaft distribution) of postsynaptic sites. Thus, the septal lesion paradigm is as strong a method for investigating synaptic rigidity as for investigating plasticity. In the intervening years, the use of embryo to adult transplantation has made it obvious that considerable reconstruction of adult brain synaptology is possible, and that many of the normal rules of connectivity are maintained (most prominently for the 'point-to-point' axonal systems). What could lead to further fruitful investigation is the extent to which the observations (e.g. relating to hierarchies of axonal preference, the need for denervation, and the involvement of glial cells) in partially deafferented adult systems, such as the septal nuclei, are retained, or modified, in face of the ingrowing fibres from embryonic transplants.

Animals↗
PubMed1989

Embryonic entorhinal transplants project selectively to the deafferented entorhinal zone of adult mouse hippocampi, as demonstrated by the use of Thy-1 allelic immunohistochemistry. Effect of timing of transplantation in relation to deafferentation.

The mouse Thy-1.1/Thy-1.2 allelic marking system is used to show that transplanted embryonic entorhinal cortex can reinnervate adult host hippocampi. The projection is limited to the appropriate terminal zones--viz. the outer two-thirds of the stratum moleculare of the dentate gyrus, and the stratum lacunosum-moleculare of the hippocampus--and extends for up to about 2 mm into the denervated host terminal field. The reconstruction of the entorhinal projections to the host requires direct contact between the embryonic donor tissue and the denervated adult host terminal field, and is dependent upon removal of the ipsilateral host entorhinal area. In the absence of an overall deafferenting host entorhinal lesion the transplanted entorhinal area forms only small local projections which are confined to areas which would have been locally deafferented as a result of direct damage to the host entorhinal afferents (i.e. during their intrahippocampal course) by the hippocampal lesion caused at the time when the transplant was inserted. The correct relative timing of deafferentation and transplantation is vital for the formation of the transplant-to-host projection. The host dendrites can be made receptive to entorhinal transplant projections by removal of the host entorhinal area at the time of transplantation. When deafferentation is performed first and transplantation is delayed, it is found that the deafferented host dendrites retain this receptivity even when deafferentation has been performed as much as two months before transplantation. Reversing the order of transplantation and deafferentation, however, shows that the transplants have only a transient ability to project to the deafferented host territory. Thus, transplants inserted and allowed to become established for one week before host deafferentation make very much reduced projections to the host, and from two weeks onwards are incapable of any detectable response to subsequent removal of the host entorhinal area. Coextensive with the formation of transplant-to-host entorhinodentate projections, the host entorhinal lesion also induces an intensification of the acetylcholinesterase staining of the host septodentate afferents in the denervated outer dentate stratum moleculare. The findings demonstrate the accurate reconstruction of a lost projection in adult brain by transplanting the appropriate type of embryonic tissue, but the results of altering the relative timing of deafferentation and transplantation raise currently unsolved questions about the nature of the competitive interactions between transplant and host axons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Fetal medial habenula transplants: innervation of the rat interpeduncular nucleus.

The effects of donor age and site of placement on the survival of fetal medial habenula (MH) transplants into adult rats hosts were examined. The innervation of the interpeduncular nucleus (IPN) in such cases was also examined. Explants of MH consisting of the medial-dorsal lip of the third ventricle were held in vitro for 1-2 days. Colloidal gold conjugated to wheat germ agglutinin was added for the last 18 hours to label the cells. Four of 16 cases with E19 derived transplants contained donor neurons. Markedly larger transplants were present in 95% of 20 cases with E16 derived transplants. Sites in the ventral midbrain were successful, while limited or no survival occurred at sites more remote from IPN. Retrograde labeling of transplant neurons was present in each case studied with HRP injection into host IPN. Colloidal gold-labeled macrophages, some oriented capillaries and GFAP-positive processes marked the donor-host interface. In EM the interface was evident only by the difference in tissue elements in the transplant versus host. Numerous synapses of Gray types I and II were present in the transplant. Excellent survival of MH neurons, donor/host interfaces, innervation of IPN by the transplant and fine structure in and around the transplants, all suggest that such preparations are suitable for further experimental analysis of the habenulo-interpeduncular system.

Animals↗