PubMed Health⌕ Search

Biomedical subjects

B Finsen

Publications and source records attributed to B Finsen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Development of microglia in the postnatal rat hippocampus.

During the prenatal development of the hippocampus, microglial cell precursors progressively occur in all subfields in accordance with known ontogenetic gradients of the region (Dalmau et al., J. Comp. Neurol. 1997a;377:70-84). The present study follows the regional distribution of these microglial cell precursors and their morphological differentiation in the rat hippocampus from birth to postnatal (P) day 18. The results demonstrate that the cellular differentiation and the subregional distribution of microglia follow the specific developmental gradients of the different parts of Ammon's horn and the dentate gyrus. Microglial cell distribution in the dentate gyrus is thus delayed compared with that in Ammon's horn. The appearance of microglia in the hippocampal subregions and differentiation of cell precursors into adult microglia occur earlier at temporal levels than at septal levels. Distribution of microglial cells follows an outside-to-inside pattern from the hippocampal fissure to the main cell layers in either Ammon's horn or the dentate gyrus. Meanwhile, the resident microglial cells located in the stratum oriens and dentate hilus at birth also increase in number and gradually disperse throughout the whole tissue of the two layers with age. In Ammon's horn, microglial differentiation occurs earlier in CA3 than in CA1. In the dentate gyrus, microglia appear earlier in relation to the external limb than to the internal limb, largely following a lateral-to-medial gradient. The differentiation and appearance of microglia in the various hippocampal and dentate subregions often correspond to the developmental stage of intrinsic and extrinsic afferent nerve fiber projections. Finally, in both Ammon's horn and the dentate gyrus, cells resembling reactive microglia are also observed and, in particular, in the perforant path projections from P9 to P18, suggesting their participation not only in phagocytosis of dead cells but also in axonal elimination and/or fiber reorganization.

Acid Anhydride Hydrolases↗
PubMed1998

Microglia and macrophages are major sources of locally produced transforming growth factor-beta1 after transient middle cerebral artery occlusion in rats.

The potentially neurotrophic cytokine transforming growth factor-beta1 (TGF-beta1) is locally expressed following human stroke and experimental ischemic lesions, but the cellular source(s) and profile of induction have so far not been established in experimental focal cerebral ischemia. This study presents the time course and a cellular localization of TGF-beta1 mRNA, visualized by in situ hybridization combined with immunohistochemical staining for microglia, macrophages, or astrocytes, on brain sections from adult spontaneously hypertensive rats subjected to transient proximal occlusion of their middle cerebral artery. Six hours after ischemia, an early and transient neuronal and microglial expression of TGF-beta1 mRNA was observed in the extraischemic cingulate and frontal cortices. Both early and protracted expression of TGF-beta1 mRNA in the caudate-putamen and neocortical infarcts and in the caudate-putamen penumbra colocalized with OX42/ED1-immunoreactive microglia and macrophages, whereas TGF-beta1 mRNA in the neocortical penumbra colocalized with OX42/ED1-immunoreactive cells of a microglial morphology. No astrocytes were double-labeled. The number of TGF-beta1 mRNA-expressing microglia and macrophages increased strongly during the first week. Thereafter, TGF-beta1 mRNA became increasingly restricted to the neocortical penumbra (3 weeks), and after 3 months it was confined to activated microglia in the anterior commissure. Our data establish activated microglia and macrophages as the major source of TGF-beta1 mRNA following experimental focal cerebral ischemia. Consequently, TGF-beta1-mediated functions may be exerted by microglia both in the early degenerative phase, and later in combination with blood-borne macrophages, in the remodeling and healing phase after focal cerebral ischemia.

Animals↗
PubMed1997

Microglial and macrophage reactions mark progressive changes and define the penumbra in the rat neocortex and striatum after transient middle cerebral artery occlusion.

Transient middle cerebral artery occlusion in rats leads to infarction of the lateral part of the striatum and adjacent neocortex, with selective neuronal necrosis in the bordering penumbral zones. Administration of glutamate, cytokine, and leukocyte antagonists have rescued mainly neocortical neurons, indicating differences in the degenerative processes. The aim of this study was, therefore, to describe the microglial/macrophage activation and polymorphonuclear leukocyte recruitment patterns and to correlate these with the ischemia-induced degenerative processes. The analysis showed significant differences in the characteristics and timing of the microglial/macrophage responses between the caudate putamen and neocortical infarct zones, the infarct zones and their associated penumbral zones, as well as between the striatal and the neocortical penumbral zone. Infiltrations with polymorphonuclear leukocytes into the infarct zones were limited and shortlasting and confined to the acutely degenerating striatum and piriform cortex. A delayed, massive infiltration with lipid phagocytes into the caudate putamen infarct markedly contrasted an early recruitment and activation of microglia/macrophages in the adjacent penumbra. Within the neocortex, a later onset of degeneration along the insular-parietal axis was marked by neuronal expression of heat shock protein and a progressive microglial activation with induction of the full repertoire of microglial activation markers, including a widespread microglial major histocompatibility complex (MHC) class II antigen expression. We interpret the present results as delineating two differentially progressing penumbral zones, which are likely to reflect differences in the underlying degenerative processes. Differences in the microglial/macrophage activation pattern attract special attention, as these cells may constitute specific targets for therapeutic intervention.

Animals↗
PubMed1997

Development of microglia in the prenatal rat hippocampus.

The distribution and appearance of microglia cell precursors in the prenatal hippocampus were examined in embryonic day 14 (E14) to E21 rats by nucleoside diphosphatase histochemistry. For comparison, the differentiation of astroglial cells was analyzed from E17 by vimentin and glial fibrillary acidic protein immunohistochemistry. Based on morphologic features, nucleoside diphosphatase-positive microglial cell precursors were classified as ameboid microglial cells and primitive ramified microglial cells. Ameboid microglia were present in the hippocampal primordium on E14. As the hippocampus developed, however, ameboid microglia gradually transformed into primitive ramified microglia, first recognized at E19. Microglial cell precursors, often related to nucleoside diphosphatase-labeled blood vessels, were particularly observed next to the pial surface on days E14 and E17 and in the highly vascularized area around the hippocampal fissure from E19. Within the brain parenchyma, the microglial cell precursors tended to be located within the differentiating cell and neuropil layers rather than in the germinative zones. The late developing dentate gyrus remained almost devoid of microglial cell precursors before birth. Vimentin-positive astroglial processes with radial orientation were observed throughout the hippocampal subregions from E17. In contrast, glial fibrillary acidic protein-positive, radial processes were barely discernible in the fimbria and the dentate gyrus before E19. The results are discussed in relation to the possible interactive role of microglial cells in central nervous tissue development and histogenesis. Regarding the origin of hippocampal microglial cell precursors, the present observations support the view that these cells may well originate from different mesodermal sources depending on time and localization.

Animals↗
PubMed1997

Morphological and immunophenotypic microglial changes in the denervated fascia dentata of adult rats: correlation with blood-brain barrier damage and astroglial reactions.

The reactions of microglial and astroglial cells to anterograde axonal degeneration were studied in the fascia dentata of adult rats from 1 to 42 days after removal of the entorhinal perforant path projection. The observations focused on the kinetics of glial activation in terms of induction of immunomolecules on the glial cells and the possible correlation between these changes and lesion-induced extravasation of plasma constituents. Normal and activated microglial cells were identified by immunohistochemical visualization of the constitutively expressed complement type 3 receptor (CR3/CD11b). Activated microglial cells were stained immunohistochemically for the inducible major histocompatibility complex (MHC) antigen class I and class II and the leukocyte common antigen LCA/CD45). Astroglial cells were identified by immunohistochemical staining for glial fibrillary acidic protein (GFAP). Blood-brain barrier (BBB) conditions were primarily evaluated by immunohistochemical staining for extravasated Immunoglobulin G (IgG), but also by intravenously injected horseradish peroxidase (HRP) and Evans Blue. Twenty-four hours after entorhinal cortex ablation, microglial cells in the perforant path terminal zones displayed an increase in CR3 immunoreactivity, changes of morphology and an induced expression of MHC antigen class I. At the same time there was a hitherto undescribed leakage of IgG through the BBB (albeit without detectable extravasation of HRP and Evans Blue). One day later microglial cells also expressed LCA, but MHC antigen class II was not induced under these degenerative conditions. The activation of microglial cells occurred prior to a noticeable hypertrophy of astroglial cells and increase in GFAP immunoreactivity, as this first became evident on Postlesional Day 2. From the results we conclude (1) that perforant path axonal degeneration induces an endothelial transcytosis of blood-borne IgG by mechanisms which cannot be envisioned by conventional HRP tracer methods and (2) that the early activation of both microglial cells and astroglial cells is likely to be initiated and later influenced by both axonal degeneration and extravasated plasma constituents. The demonstration of an early induction of immunomolecules on activated microglial cells and extravasation of blood borne molecules might moreover form the basis for a correspondingly early intervention aiming to regulate microglial immunomolecule, cytokine, and growth factor gene expression in the affected areas.

Animals↗
PubMed1997

Enriched immune-environment of blood-brain barrier deficient areas of normal adult rats.

The circumventricular organs (CVOs) in the brain are without a blood-brain barrier (BBB) and as such directly exposed to blood plasma constituents and blood-borne pathogens. In light of previous studies showing discrepancies regarding the immunocompetence of these organs, we initiated the present study to provide a comprehensive immunohistochemical analysis of the cellular expression of immune-associated antigens within the pineal gland, area postrema and the subfornical organ. In all CVOs, subpopulations of cells morphologically similar to complement receptor type 3 immunoreactive microglial/macrophage cells expressed major histocompatibility complex (MHC) class II antigen, leucocyte common antigen (LCA/CD45), as well as CD4 and ED1 antigen. Based on morphological criteria the MHC class II antigen expressing cells could be grouped into a major population of classical parenchymal and perivascular ramified microglial cells and a minor population presenting itself as scattered or small groups of rounded macrophage-like cells. CD4 and ED1 antigen were expressed by both cell types. CD45 was preferentially expressed by macrophage-like cells. MHC class I antigen was expressed by the vascular endothelium in both BBB-protected and BBB-deficient areas and was additionally present as a lattice-like network throughout the BBB-deficient parenchyma in all CVOs. The results suggest that the BBB-free areas of the brain besides being constantly surveyed by blood-borne macrophages, possess an intrinsic immune surveillance system based on resting and activated microglial cells, which may function as a non-endothelial, cellular barrier against blood-borne pathogens.

Animals↗
PubMed1997

Triple immunosuppression protects murine intracerebral, hippocampal xenografts in adult rat hosts: effects on cellular infiltration, major histocompatibility complex antigen induction and blood-brain barrier leakage.

Recently we reported protection of intracerebral mouse to rat hippocampal xenografts upon treatment with a combination of cyclosporin A, prednisolone and azathioprine. These findings are now supported in an extended analysis of graft-infiltrating cells. Host T-cell and macrophage infiltration and the immunocytochemical level of cellular expression of major histocompatibility complex class I and II antigens, measured by densitometric analysis, were compared between recipient rats receiving cyclosporin A alone or cyclosporin A in combination with prednisolone and azathioprine. The combination therapy resulted in a much improved survival of the xenografted hippocampal tissue with preservation of organotypic granule and pyramidal cell layers. Graft infiltration by T-cells and macrophages was significantly lower and the level of major histocompatibility complex class I and II antigen expression by the infiltrating cells markedly reduced. Lower expression of donor-type major histocompatibility complex class I antigen was also found in the xenografts in the trimedicated recipients, together with reduced blood brain barrier leakage and astrogliosis at the host-graft interface. The results demonstrate the benefits of using combined immunosuppressive strategies for protection of histoincompatible brain xenografts in the central nervous system.

Animals↗
PubMed1996

No loss of hippocampal hilar somatostatinergic neurons after repeated electroconvulsive shock: a combined stereological and in situ hybridization study.

Electrically induced seizures with anesthesia and muscle relaxation (ECT) is commonly used in the therapy of psychotic depression in humans. Unmodified electroshock (ECS) is used as a model for epilepsy in the rat. In several seizure models of epilepsy, in particular the dentate hilar somatostatin-containing (SSergic) neurons have been found to undergo degeneration. To assess the potential loss of SSergic hilar neurons after repeated ECS, 10 rats were given 110 ECS, one per day, 5 days a week. One day after the last ECS the rats were anesthesized, perfused, the brains cut on a vibratome and prepared for nonradioactive in situ hybridization for somatostatin along with five control rats. Like rats given 10-36 ECS in earlier studies, the ECS-treated rats displayed a markedly increased neuronal hybridization labeling when compared with control rats. The total number of dentate hilar SSergic neurons of each rat was estimated using the optical disector technique. The mean number of hilar SSergic neurons in the ECS-treated rats was 12,785, compared to 12,392 in the control rats. The total number of hilar SSergic neurons in ECS-treated versus control rats was not significantly different (Student's t test; t value = .35; p = .74). We conclude that repeated ECS treatment does not cause loss of hilar SSergic neurons.

Animals↗
PubMed1996

Estimation of the number of somatostatin neurons in the striatum: an in situ hybridization study using the optical fractionator method.

Somatostatin-containing neurons of the striatum constitute fewer than 5% of the total neuronal population. Their involvement in the feedforward inhibition of the spiny projection neurons, the modulation of other interneurons, and the regulation of regional blood flow indicates that this small population of neurons plays an important role in the processing of information in the striatum. As a first step in developing a quantitative structural framework within which a more rigorous analysis can be made of the functional circuitry of the striatum, we used modern unbiased stereological techniques to make estimates of the total number of neurons expressing mRNA for somatostatin in the striatum of rats. The strategy developed involved the application of the optical fractionator technique to relatively thick tissue sections that were hybridized in situ with a relatively short oligonucleotide probe conjugated to a nonradioactive reporter molecule. The approach is generally applicable to other subpopulations of in situ hybridized cells in other parts of the brain and can provide a link between molecular neurobiology and stereology. The mean total number of neurons on one side of the striatum was estimated to be 21,300. An analysis of the sampling scheme indicated that counting no more than 200 neurons in a systematic sample of not more than 15 sections per individual results in an estimate with a precision that is more than sufficient for comparative and experimental studies. The issues that must be considered when analyzing in situ hybridized tissue with modern stereological methods, the interpretive caveats inherent in the resulting data, and the unique perspectives provided by data like that presented here for striatal somatostatin neurons are discussed.

Animals↗
PubMed1996

In situ hybridization for somatostatin mRNA in the adult rat: cingulate, insular, prepiriform, perirhinal, entorhinal, and retrosplenial cortical regions.

The expression of somatostatin mRNA within the allocortex of the rat was examined by in situ hybridization with an alkaline phosphatase labeled probe. We sought to determine whether parcellation of the allocortex could be based upon the number and laminar location of the hybridized cells and to contrast the allocortical features with those of the isocortical areas. The cingulate region was characterized by intense, moderate, and faint cells, small to medium in size throughout the laminae. The retrosplenial region demonstrated a somewhat stratified appearance with an abundance of cells expressing somatostatin mRNA in the upper portion of the composite layer II-IV and also in the upper portion of layer VI. The insular region displayed more heterogeneity. The distribution of the cells hybridized for somatostatin mRNA formed distinctive configurations within the insular region (dorsal and ventral agranular insular areas) with no obvious generality. The perirhinal area resembled the ventral agranular insular area, and the cell distribution of the entorhinal and prepiriform areas displayed a common characteristic in that the primary axis of the perikarya of somatostatin mRNA expressing cells within the lower layers were oriented at almost every possible angle. The conclusion of the investigation is that in situ hybridization for somatostatin mRNA provides a means by which the areal boundaries within the allocortex may be drawn.

Animals↗
PubMed1996

Microglial reactions to retrograde degeneration of tracer-identified thalamic neurons after frontal sensorimotor cortex lesions in adult rats.

Thalamic neuronal degeneration after neocortical lesions involve both anterograde and retrograde components. This study deals with the thalamic microglial response after neocortical aspiration lesions, using fluorogold fluorescent prelabeling, to identify retrogradely degenerating thalamocortical neurons, combined with histochemical or immunohistochemical staining of microglial cells. Adult male Wistar rats were injected with the retrograde fluorescent tracer fluorogold, in the right sensorimotor cortex (forepaw area) in order to retrogradely label thalamic neurons projecting to this area. After 1 week, the fluorogold injection site was removed by aspiration, axotomizing at the same time the thalamic projection neurons now retrogradely labeled with fluorogold. After 3, 7, 14, and 28 days the animals were killed and processed for nucleoside diphosphatase histochemistry or complement type 3 receptor immuno-histochemistry and class I and II major histocompatibility complex immunohistochemistry using OX42, OX18, and OX6 antibodies. The histological analysis showed a prominent and progressive nucleoside diphosphatase-, OX42-, and OX6-positive microglial cell response in the ventrolateral, posterior, and ventrobasal thalamic nuclei with ongoing retrograde and anterograde neuronal degeneration. Initially the reactive microglia had a bushy morphology and were succeeded by ameboid microglia and microglial cluster cells as the reaction progressed. However, in the reticular thalamic nucleus, which suffered exclusively anterograde neuronal degeneration, a different picture was seen with only bushy microglia. The neurons undergoing retrograde degeneration in the ventrolateral, posterior, and ventrobasal thalamic nuclei were retrogradely labeled by the fluorogold tracer. Individual nucleoside diphosphatase-, OX42-, or OX6-positive microglial cells extended long cytoplasmic processes surrounding fluorogold-labeled neurons and had in some cases apparently phagocytized these. Several microglial cells were thus double-labeled with nucleoside diphosphatase or OX42 and fluorogold. In addition, small nucleoside diphosphatase-positive, fluorogold-labeled perivascular cells were observed in the neocortex near the fluorogold-injected and ablated neocortical areas and in the ipsilateral thalamus. This study demonstrates: (1) that the microglial response to thalamic degeneration after neocortical lesion is graded with a limited reaction to the well-known massive anterograde axonal degeneration and a more extended reaction to the axotomy-induced retrograde cell death; and (2) that also perivascular cells and possibly macrophages may contribute to this reaction, as seen by uptake of fluorogold from axotomized neurons in the degenerating thalamic nuclei.

Acid Anhydride Hydrolases↗
PubMed1996

Reduction of the microglial cell number in rat primary glial cell cultures by exogenous addition of dibutyryl cyclic adenosine monophosphate.

The present work examined the effects induced by dibutyryl cyclic adenosine monophosphate (dB-cAMP) on microglial cells in primary glial cell cultures from newborn rats. Microglial cells were identified by OX42 immunohistochemistry and nucleoside diphosphatase histochemistry. Double staining for astrocytes was carried out by combination with glial fibrillary acidic protein immunolabeling. Addition of 0.25 mM dB-cAMP to the cultures decreased the microglial cell number about sixfold. The findings suggest that the effect of dB-cAMP on the microglial cells might be either a direct action of dB-cAMP on the microglial cells or an indirect effect mediated by the astroglial cells.

Acid Anhydride Hydrolases↗
PubMed1995

Prevention of mouse-rat brain xenograft rejection by a combination therapy of cyclosporin A, prednisolone and azathioprine.

Embryonic mouse hippocampal tissue was grafted as tissue blocks to the hippocampal region of adult rats and the effect of two different immunosuppressive treatments compared. Immunosuppression with cyclosporin A, prednisolone and azathioprine or with cyclosporin A alone was compared with placebo treatment. Eight weeks' postgrafting medication with cyclosporin A, prednisolone and azathioprine had resulted in survival of 14 out of 15 grafts (93%), compared with 11 out of 14 (79%) in the group treated with cyclosporin A alone. Only 2 out of 13 grafts (15%) survived in placebo-treated animals. Transplants in the trimedication group displayed distinct cell and neuropil layers and only minimal cellular infiltration by leukocyte common antigen-expressing cells, whereas grafts in cyclosporin A- and placebo-treated groups were densely infiltrated. The results are discussed in relation to the need for extended immunosuppressive and antiinflammatory therapies after intracerebral grafting of histoincompatible tissues.

Animals↗
PubMed1995

Organotypic slice cultures of the rat striatum: an immunocytochemical, histochemical and in situ hybridization study of somatostatin, neuropeptide Y, nicotinamide adenine dinucleotide phosphate-diaphorase, and enkephalin.

In order to establish an in vitro model of Huntington's disease, we prepared slice cultures of striatal tissue from newborn rats. The striatal cultures were grown for 12-39 days in the absence of any other brain tissue. The presence of specific cell markers was shown by immunocytochemistry, histochemistry and in situ hybridization with alkaline-phosphatase-labeled oligonucleotide probes. We focused on (1) the medium-sized, aspiny interneurons, which in vivo express the neuropeptides somatostatin and neuropeptide Y and the nitric oxide synthesizing enzyme nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase, and which are spared in Huntington's disease and (2) the enkephalinergic, medium-sized projection neurons, which are particularly vulnerable in Huntington's disease. Similar basic morphologies of the presumed interneurons and double staining of NADPH-diaphorase positive and somatostatin immunoreactive neurons suggest that the two neuropeptides and NADPH-diaphorase are extensively colocalized in the cultures, as in vivo. In the newborn rats, included as controls, a patch-matrix distribution of the NADPH-diaphorase staining is described for the first time. In the striatal slices the distribution of the NADPH-diaphorase staining stayed uneven after 3-5 weeks in culture, with areas almost devoid of staining alternating with more heavily stained areas. This pattern may represent an intermediate stage between the patch-matrix distribution in the newborn and the homogeneous staining in the adult rat striatum. From quantitative estimates we found the same mutual rank order of the numbers of neuropeptide Y- and somatostatin-immunoreactive neurons and NADPH-diaphorase positive neurons in vivo and in vitro. Both in the slice cultures and in the brain, the number of enkephalin mRNA-containing neurons significantly exceeded that of neuropeptide Y- and somatostatin mRNA-containing neurons. This implies that the mutual distribution of presumed interneurons and projection neurons was preserved in the slice cultures. Comparison of cell numbers per unit volume showed that, in the cultures, the number of presumed interneurons, with the exception of NPY mRNA-containing neurons, significantly exceeded that in vivo. In contrast, the enkephalin mRNA-containing neurons, which in vivo are projection neurons, were significantly fewer in the cultures. The relative loss of projection neurons and preservation of interneurons in single slice cultures of striatal tissue apparently mimick some of the neurodegenerative changes of Huntington's disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Cytokines in cerebral ischemia: expression of transforming growth factor beta-1 (TGF-beta 1) mRNA in the postischemic adult rat hippocampus.

Transient global cerebral ischemia induces selective neuronal degeneration in the adult rat hippocampus, which is both preceded and accompanied by activation of microglia and astrocytes. Altered expression patterns of cytokines and growth factors might influence the postischemic neuron-glial interactions as well as the degenerative neuronal processes. Northern blotting of hippocampal tissue from ischemic animals revealed elevated levels of transforming growth factor beta-1 (TGF-beta 1) mRNA, and in the present in situ hybridization study we examine the endogenous expression and cellular localization of TGF-beta 1 mRNA in the adult rat hippocampus at various intervals following 10 min of global cerebral ischemia. Six hours after ischemia, a diffuse expression of TGF-beta 1 mRNA was found throughout the brain, which further intensified until Day 2 and thereafter subsided. In parallel, a massive increase of signal was observed in the hilus fascia dentata from Day 1 and in area CA1 from Day 2 to 4, both areas displaying selective neuronal degeneration. Peak levels of TGF-beta 1 mRNA were found in the hilus around Day 4, whereas expression in the CA1 area persisted through Day 21, the latest time point examined. A similar biphasic response, consisting of a transient, generalized reaction and a persistent lesion-associated activation in areas undergoing selective neuronal degeneration, was previously described for microglia and is reconfirmed in the present study. Cells of the microglial/macrophage lineage thus include the potent modulatory cytokine TGF-beta 1 in their potential repertoire of responses to both CNS activation and lesioning.

Animals↗
PubMed1994

Parcellation of cortical areas by in situ hybridization for somatostatin mRNA in the adult rat: frontal, parietal, occipital, and temporal regions.

The expression of somatostatin mRNA within the neocortex of the rat was examined by in situ hybridization with an alkaline phosphatase-labeled probe. We sought to determine whether parcellation of the neocortex could be based upon the number and laminar location of the hybridized cells. Our investigation demonstrated that the boundaries of the neocortical areas can be determined by the distribution pattern of neurons expressing somatostatin mRNA. Few hybridized cells were located within layer IV, and this sparsity of cells within their wide granular layer marked the primary sensory areas. The occipital region was stratified, with intensely labeled cells in layers II/III and VI and faintly labeled cells in layer V. The parietal region carried a similar stratification, but more space between intensely labeled cells in layers III and V and between layers V and VI gave the region a three-tiered appearance. The temporal region displayed intensely labeled cells dispersed throughout layers III and VI and many in layer V as well as those faintly labeled without any breaks between the laminae. The distribution of the cells hybridized for somatostatin mRNA formed two configurations within the frontal region. It was difficult to identify any lamination in the first area, whereas the second area demonstrated a stratification reminiscent of the parietal region, but with only two tiers. The conclusion of the investigation is that in situ hybridization fro somatostatin mRNA provides an exceptional means by which the area boundaries within the neocortex may be drawn.

Animals↗
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↗