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Biomedical subjects

J Zimmer

Publications and source records attributed to J Zimmer.

At least 127 records · Page 7Linked to original sources
PubMed1990

Histochemical demonstration of purine nucleoside phosphorylase (PNPase) in microglial and astroglial cells of adult rat brain.

The histochemical localization of enzymes associated with purine nucleoside metabolism indicates that glial cells might participate in the regulation of these compounds in the central nervous system. In the present study we examined the histochemical localization of purine nucleoside phosphorylase (PNPase) in sections from adult rat brain. Some sections were also sequentially stained immunocytochemically for astroglial or microglial cells utilizing glial fibrillary acidic protein (GFAP) or OX-42 antibodies, respectively. Our observations showed that PNPase was restricted to glial cells, whereas neurons always remained negative. Brain sections stained for both PNPase and GFAP showed that the GFAP-positive astroglial cells were always PNPase positive. Other PNPase-positive but GFAP-negative cells were also observed. These cells resembled microglial cells, and brain sections reacted for both PNPase and OX-42 confirmed this by showing that the major part of OX-42-positive microglial cells were PNPase positive. In these sections, the PNPase-positive but OX-42-negative cells present resembled astroglial cells. From our double staining experiments, we conclude that PNPase is present in both astroglial and microglial cells in normal adult brain.

Animals↗
PubMed1990

Neural grafting to ischemic and excitotoxic, hippocampal lesions in the adult rat.

Results of neural grafting to excitotoxic and ischemic lesions of the adult rat hippocampus is reviewed with particular emphasis on the exchange of host-transplant nerve connections. Based on observations obtained by a variety of tracing techniques about 6 weeks after--(i) grafting of pieces of neonatal fascia dentata to one week old ibotenic acid lesions of the adult rat fascia dentata, (ii) grafting of suspensions of late fetal CA3 cells to one week old ibotenic acid lesions of the adult rat CA3--and (iii) grafting of suspensions of late fetal CA1 cells to one week old ischemic lesions of the adult rat CA1, we conclude that axon-sparing lesions of the mentioned types enhance the growth of adult host brain axons of the so called point-to-point type into neural grafts. We interpret these findings as the result of an improved capability of adult host brain axons to participate in the graft host interaxonal competition for synaptic sites in the developing neural grafts. At the same time an extensive growth of graft CA3 and CA1 axons into the host brain was demonstrated.

Animals↗
PubMed1989

Transplantation of immature murine brain tissue into the anterior eye-chamber of adult rats.

Embryonic mouse hippocampi (E17) were placed in the anterior eye chamber of young adult rats. The transplants were photographed twice a week. Initially the transplants increased in size, thereafter focal bleeding occurred and later regression of the transplants was seen. Regression continued until the transplants were no longer macroscopically visible. At this time the eyes were prepared for histological examination. Comparison of these transplants with immature rat hippocampi transplanted to the anterior eye chamber of rats, and with mouse-rat in vitro co-cultures suggests that the regression is a result of an immunological response.

Animals↗
PubMed1989

Fetal cortical transplants reduce the thalamic atrophy induced by frontal cortical lesions in newborn rats.

Fetal neocortical tissue was grafted into frontal cortex lesion cavities made in newborn rats. After survival periods extending up to 14 months, volumetric measurements of the total thalamus and of the lateral, medial and anterior thalamic compartments showed an amelioration of the thalamic atrophy that normally is found after cortical lesions. These results correspond to previous findings demonstrating interconnections between fetal cortical transplants and the host thalamus.

Animals↗
PubMed1989

Neural grafting to ischemic lesions of the adult rat hippocampus.

The purpose of this study was to examine the structural and connective integration of developing hippocampal neurons grafted to ischemic lesions of the adult rat hippocampus. The 4-vessel occlusion model was used to cause transient cerebral ischemia which damages CA1 pyramidal cells in the dorsal hippocampus, but spares nonpyramidal neurons and afferents in the area. One week later, cell suspensions were made from the CA1 region of fetal (E18-20) rats and injected stereotaxically into the lesion. The recipient brains were examined 6 weeks to 6 months later for survival, morphology, and intrinsic and extrinsic connections of the grafts. The methods used included cell stains, histochemical staining for acetylcholinesterase (AChE), immunocytochemical staining for neuropeptides (cholecystokinin (CCK), somatostatin (SS), enkephalin (Enk) and an astrocytic marker, glial fibrillary acidic protein (GFAP), as well as tracing by retrograde axonal transport of fluorochromes and light and electron microscopy of anterograde axonal degeneration. The grafts survived well (80%) and were often quite large. They were well integrated in the lesioned host brain area, contained both pyramidal cells and neuropeptidergic neurons and displayed a near normal GFAP immunoreactivity for astrocytes. The latter contrasted the dense gliosis of the host ischemic lesion. Judged by the AChE staining the grafts were innervated by cholinergic host septohippocampal fibers. Ingrowth of host hippocampal commissural fibers was demonstrated by Fink-Heimer staining for degenerating nerve terminals following acute lesions of the hippocampal commissures. At the ultrastructural level degenerating, electron dense terminals of host commissural origin were found even deep inside the graft neuropil in synaptic contact with mainly dendritic spines. A transplant efferent connection to the host brain was demonstrated by retrograde fluorochrome tracing and consisted of a homotypic projection to more posterior levels of the ipsilateral host CA1 and subiculum. Minor abnormal, efferent projections to the host dentate molecular layer were shown in Timm staining. We conclude that fetal CA1 neurons grafted to one week old ischemic lesions of the dorsal CA1 in adult rats become structurally well incorporated and can establish nerve connections with the host brain.

Animals↗
PubMed1989

Enhanced host perforant path innervation of neonatal dentate tissue after grafting to axon sparing, ibotenic acid lesions in adult rats.

This study examines to which extent developing dentate granule cells grafted into excitotoxic lesions of the adult rat fascia dentata can be appropriately innervated by the host brain. The lesions were induced by focal injections of ibotenic acid (IA) and resulted in localized dentate and hippocampal neuronal cell death, but sparing of the afferent connections, now deprived of their targets. One week later pieces of fascia dentata from newborn rats were grafted into the lesions. After 6 weeks to 9 months the recipient brains were processed and analyzed by cell stain, histochemistry, immunohistochemistry, anterograde nerve fiber degeneration methods, and electron microscopy. Dentate grafts survived well in the lesion area and became organo-typically organized. They contained the normal nerve cell types of the fascia dentata and hilus (CA4), including the peptidergic somatostatin-, cholecystokinin- and enkephalin-reactive ones. The grafts were innervated by AChE-positive, cholinergic fibers from the host septum, and perforant path fibers from the host entorhinal area. The presence of the latter were demonstrated by Timm staining and light and electron microscopy of anterograde axonal degeneration. When the extent and density of the host perforant path innervation was examined and mapped at the electron microscopical level the grafts in the IA-lesions were found to receive a more extensive and denser host innervation than grafts placed in the normal fascia dentata of adult rats without a preceding axon-sparing ibotenic acid lesion. In this way the results demonstrate that certain lesion types can enhance the innervation of intracerebral grafts by already mature neural pathways of the point-to-point type.

Acetylcholinesterase↗
PubMed1989

Regional assignment of the human loci for uvomorulin (UVO) and chymotrypsinogen B (CTRB) with the help of two overlapping deletions on the long arm of chromosome 16.

Using cDNA probes for the human uvomorulin (UVO) and rat chymotrypsinogen B (CTRB) genes, we have analyzed two overlapping interstitial deletions on human chromosome 16q by Southern blot analysis. One deletion, with breakpoints at 16q22.1 and 16q22.3, results in loss of the UVO locus. The second deletion, whose breakpoints are at 16q22.1 and 16q23.2, leads to loss of the CTRB locus. Therefore, UVO resides between both proximal deletion breakpoints within band 16q22.1, whereas CTRB is located between both distal breakpoints at 16q22.3 and 16q23.2.

Blotting, Southern↗
PubMed1988

Ultrastructural organization of normal and transplanted rat fascia dentata: I. A qualitative analysis of intracerebral and intraocular grafts.

Few studies have dealt with the general ultrastructure and synaptic organization of grafted brain tissue. This study was therefore performed to extend current light microscopic observations on intracerebral and intraocular grafts of hippocampal tissue to the ultrastructural level. Blocks of tissue containing the hippocampus and fascia dentata from day 21 embryonic rats were grafted into the brain of developing and adult rats and to the anterior eye chamber of adult rats. After 100 or 200 days of survival the recipient rat brains or eyes were processed for electron microscopy. Tissue containing the graft dentate molecular layer and adjacent granule cell layer was selected for ultrastructural analysis, together with a few samples of the hilus and CA3. Normal dentate tissue was analyzed as control. At the light microscopic level most intracerebral and intraocular grafts displayed an organotypic organization with clearly recognizable cell and neuropil layers. Under the electron microscope the grafted granule cells had normal-appearing dendrites bearing the normal types of spines and forming the normal types of synapses. This was the case even in the absence of the normal major extrinsic afferents like the perforant path. The graft dentate granule cells formed axons and terminals with characteristics of the normal mossy fiber system in the hilus and CA3, in addition to aberrant supragranular mossy fiber terminals known from light microscopic studies of dentate transplants. Abnormal structures included a few dendritic growth cones and an increased occurrence of polyribosomes in spines. Their occurrence indicates ongoing dendritic plasticity even 100 days after transplantation. There was also an increased density of glial elements, particularly in the intraocular grafts. In some of these grafts the granule cells displayed immature traits in terms of nuclear indentations. Dentate interneurons of the basket cell type were present in both the intracerebral and the intraocular grafts. We conclude that grafted dentate granule cells, in different surroundings and without the normal, major perforant path input, can develop a basically normal cellular morphology, which includes the normal ultrastructural characteristics of the dendrites with spines and synapses, and the mossy fibers and its terminals.

Animals↗
PubMed1988

Ultrastructural organization of normal and transplanted rat fascia dentata: II. A quantitative analysis of the synaptic organization of intracerebral and intraocular grafts.

As part of an ultrastructural analysis of the normal rat fascia dentata and intracerebral and intraocular dentate transplants the synapses in the dentate molecular layer were quantified. Hippocampal and dentate tissue from 21-day-old rat embryos were grafted into the brain of developing and adult rats and to the anterior eye chamber of adult rats. After 100 or 200 days of survival the recipient rat brains and the recipient eyes were processed for electron microscopy, and the graft dentate molecular layer with the adjacent granule cell layer selected for ultrastructural analysis. Tissue from the dentate molecular layer of normal adult rats served as controls. The dentate synapses were classified as asymmetric (Gray's type 1) or symmetric (Gray's type 2), and according to the postsynaptic element (cell body, dendritic shaft, dendritic spine). The spine synapses were further classified into simple and complex types according to the spine-terminal configuration. Also, the length of synaptic contacts of the individual synaptic types was measured in some grafts, just as the percentage of the cross sectional area of the neuropil covered by blood vessels. The results showed that the synaptic density, expressed as number per unit area of neuropil, to a large extent was the same within the different parts of the normal dentate molecular layer. Compared with this the synaptic density was reduced with 16.4% in dentate molecular layer of the intracerebral graft, primarily because of a 17.6% reduction of simple synapses on dendritic spines and almost halving of the symmetric synapses on dendritic shafts. The synaptic density was independent of the age of the recipient, the intracerebral location of the graft, and the survival time. Although the synaptic length of some of the individual synaptic types increased, this did not compensate for the loss of synapses. In the intraocular grafts the synaptic density was lower than in the intracerebral grafts. Despite the reduced synaptic density, which mainly involved two synaptic types, we conclude that grafted dentate granule cells can develop a remarkably normal, ultrastructural synaptic organization even in the absence of major afferent inputs. This outcome must accordingly be achieved by reorganization of the available intrinsic afferents.

Animals↗
PubMed1988

Fetal neocortical transplants grafted to the cerebral cortex of newborn rats receive afferents from the basal forebrain, locus coeruleus and midline raphe.

Fetal cerebral neocortex (E15-17) was grafted into the cerebral hemisphere of newborn (0-1 day old) rats. Grafts were placed into cortical aspiration lesion cavities made immediately prior to grafting. At maturity, transplant afferents were examined by injecting the retrogradely transported fluorescent dyes diamidino yellow and fast blue into the grafts. Retrogradely-labeled neurons were histologically observed within several regions of the host brain including the basal forebrain, locus coeruleus and dorsal raphe areas. The topographical distribution within these areas resembled the normal labeling patterns described in previous reports.

Animals↗
PubMed1988

Hippocampal neurons grafted to newborn rats establish efferent commissural connections.

The formation of commissural projections from developing rat hippocampal neurons grafted to the hippocampus of newborn littermates was examined by retrograde axonal transport of the fluorescent dye Fluorogold (FG). At six weeks of age the recipients received two injections of FG in the hippocampus contralateral to the graft. This resulted in labelling of normal, commissurally projecting neurons in the dentate hilus and CA3 of the host hippocampus. Neurons in several transplants were also labelled, and based on morphology and location they were identified as CA3 and dentate hilus neurons.

Acetylcholinesterase↗
PubMed1988

Xenografting of fetal mouse hippocampal tissue to the brain of adult rats: effects of cyclosporin A treatment.

This study examines the effect of the immunosuppressive drug Cyclosporin A (CyA) on the survival and differentiation of solid grafts of fetal (E16-17) mouse hippocampi transplanted to the brain of adult rats. The CyA was given as daily subcutaneous injections of 20 mg/kg from the day before transplantation with reduction of the dose to 15 mg/kg after 14 days. Five weeks after transplantation neuron containing xenografts were recovered in 11 out of 17 CyA-treated recipients (65%). After 8 weeks 9 out of 21 grafts were found (43%). In the control groups, treated only with the vehicle olive oil, 8 out of 14 xenografts were recovered after 5 weeks survival (36%) and only 3 out of 17 after 8 weeks (18%). All xenografts were infiltrated with mononuclear lymphocytic-like cells, but the infiltration was least extensive and least dense in the CyA treated animals. An observed correlation between this cellular infiltration and the gliosis in the xenografts suggested that CyA also directly or indirectly influenced the glial reaction. Most surviving xenografts were located next to the lateral ventricles or the choroid fissure. They were organotypically organized with identifyable cell and neuropil layers, and their connectional organization was similar to rat and mouse allografts grafted to adult recipients. In the absence of major extrinsic afferents the intrinsic pathways observed with Timm staining had reorganized according to known principles for aberrant growth and collateral sprouting. Ingrowth of extrinsic host afferents was only demonstrated for AChE positive host fibers. We conclude that CyA treatment of adult rat recipients can increase the survival of intracerebral fetal mouse hippocampal xenografts and reduce the histological signs of rejection. Xenografting combined with CyA treatment thereby permits the use of a wider spectrum of donor neurons for studies of neuronal interaction and repair.

Acetylcholinesterase↗
PubMed1988

Xenografts of mouse hippocampal tissue. Exchange of laminar and neuropeptide specific nerve connections with the host rat brain.

Immature hippocampal and fascia dentata tissue from embryonic and newborn C57 mice was grafted to the hippocampal region of newborn Kyoto rats. The age of the donor mice varied from embryonic day 13 to the day of birth, and the recipient rats from the day of birth up to 2 days. After survival times of from 5 weeks to 1 year the recipient brains were histologically processed for the tracing of host-xenograft connections by silver staining and electron microscopy of anterograde degeneration, AChE histochemistry, immunohistochemical demonstration of the neuropeptides CCK and enkephalin, and the histochemical Timm sulphide silver method, as well as stained by ordinary cell and fiber stains. The survival of the xenografts depended on the donor age, with less than 10% survival for newborn donors and 60-69% for E13-16 donors. The surviving xenografts developed an organotypic organization and retained a mouse-specific CCK-reactivity in the associational hilodentate system and the dentate mossy fibers. Judged by their positive AChE histochemistry most xenografts received a host rat cholinergic projection when placed in normal cholinoreceptive areas, including areas outside the normal reach of the septo-hippocampal system like the neocortex. Xenografts encroaching on the trajectory of the host rat commissural and perforant path projections or their terminal fields in fascia dentata received laminar and neuropeptide specific host projections. Electron microscopy of host rat perforant path fibers traced to the xenograft dentate molecular layer confirmed the laminar distribution and revealed numerous asymmetric synaptic contacts with spines. An efferent xenograft projection of CCK-reactive mouse mossy fibers into the host CA3 mossy fiber layer demonstrated that this cross-species, mouse to rat innervation also applied to the normal developmental rules, despite the, for the rat abnormal, CCK-content. The formation of laminar and neuropeptide specific mouse-rat nerve connections demonstrates the potentials of intracerebral neuronal grafting in basic and applied neurobiological research by providing new experimental models for the analysis of developmental and functional interactions between nerve cells.

Age Factors↗