PubMed Health⌕ Search

Biomedical subjects

A Seiger

Publications and source records attributed to A Seiger.

At least 91 records · Page 5Linked to original sources
PubMed1989

Morphological distribution of MBP-like immunoreactivity in the brain during development.

Myelin-basic protein (MBP)-like immunoreactivity was studied during development from postnatal day 1 to day 21 as a marker for the myelination process in the rat brain. Using monoclonal MBP antibodies, the caudo-rostral successive progression of MBP immunoreactivity was mapped in 1-, 7-, 14-, and 21-day-old animals using fluorescence microscopy of both coronal and sagittal sections. At 1 day of age, MBP-immunoreactive single fibers were seen in the lower brain stem, especially in formatio reticularis, whereas the rest of the brain was negative. In 1-week-old animals, MBP-positive fibers extended all the way into frontal cortex, but still in sparse arrays of single fibers with the largest number at the brain stem level. The 2-week stage showed a dramatic increase in the number of MBP-immunoreactive fibers. At the brain stem level, MBP-positive fiber plexuses were mixed with MBP-positive longitudinal axonal pathways. In cerebellar cortex, positive fibers began to radiate out from the white matter into the grey matter. A dense network of MBP-positive fibers was located in thalamus, and dense fluorescent fiber bundles were seen in capsula interna piercing through striatum. In cerebral cortex positive radiating fibers were considerably more numerous than at the previous stage. At the age of 3 weeks, MBP-immunoreactive fibers could be seen in networks and bundles in all parts of the brain. In the brain stem, a dense plexus of positive fibers filled formatio reticularis. In cortex cerebelli and cortex cerebri, a high density of radiating positive fibers was found. In striatum, a sparse distribution of single fibers was found in the neuropil surrounding the now strongly positive bundles of capsula interna. MBP-like immunoreactivity was followed during postnatal rat brain development and seemed to serve as a good indicator of progression of the myelinization process. With the excellent signal-to-noise ratio and the detailed morphological description of the distribution of MBP-like immunoreactivity, the present report can serve as a reference for studies of pathological disturbances of myelination in CNS as they relate to mechanical, chemical or hormonal perturbations.

Animals↗
PubMed1989

Morphological and electrophysiological studies of human hippocampal transplants in the anterior eye chamber of athymic nude rats.

Human fetal hippocampal tissue from normal women was obtained following elective abortion in the 8th to the 11th week of gestation. The hippocampal tissue was transplanted to the anterior chamber of the eye of adult athymic nude rats, where it was allowed to develop for up to 9 months before histological and electrophysiological evaluation. The transplants were revascularized from the host iris and many grew extensively in oculo. Large neurons were present in all transplants. Immunohistochemical studies revealed glutamic acid decarboxylase-containing terminals and clusters of gamma-aminobutyric acid-positive nerve cell bodies within the transplants, as well as scattered tyrosine hydroxylase-positive and acetylcholinesterase-containing fibers. Single neurons recorded extracellularly from transplants 4-9 months in oculo showed a slow spontaneous discharge, with both complex and single action potentials. Stimulation of the transplant surface evoked a small initial wave followed by a larger and longer-lasting field potential, similar to that seen in hippocampus in situ. A conditioning-testing paradigm was used to evaluate the presence of inhibitory circuitry in the hippocampal transplants. Significant suppression of the evoked test response was seen with interstimulus intervals ranging from 20 to 500 ms. Superfusion of enkephalin (100-300 nM) or penicillin (1600 U/ml) increased slow-wave activity, as did tetanic electrical stimulation. These treatments appeared to generate ictal-like activity, which in some cases persisted as interictal spikes. Illumination of the retina also increased neuronal activity, presumably by reflex activation of cholinergic afferents from the parasympathetic innervation of the iris. Taken together, our data suggest that fragments of hippocampus from aborted first trimester human fetuses, grafted to the eye chamber of rodent hosts, develop many organotypic histological and physiological features. This preparation may provide a unique means for the study of neurobiological properties of human brain in both normal and disease states.

Animals↗
PubMed1989

Collection and use of fetal central nervous system tissue.

A recent promising development in the field of central nervous system (CNS) tissue transplantation has suggested the use of human fetal CNS tissue from first trimester abortions for xenografting/explantation. Such experiments would certainly expand our knowledge of the normal developmental mechanisms in the human CNS, and allow studies of various indices of maturation and CNS function. However, the suggestion is looked upon with hesitance for ethical, legal and perhaps even for scientific reasons. The initial experiments have been very valuable, though, for our understanding of the structural and functional development of the human CNS, and several legal and ethical concerns have been addressed in working out the procedures for retrieving such tissue. This article tries to put our present knowledge in the right perspective of scientific achievements and potential, legal restrictions and ethical concerns.

Abortion, Induced↗
PubMed1989

Human fetal mesencephalic tissue grafted to dopamine-denervated striatum of athymic rats: light- and electron-microscopical histochemistry and in vivo chronoamperometric studies.

Human fetal mesencephalic tissue obtained from elective first-trimester abortions was grafted to 6-hydroxydopamine-denervated striatum of athymic (nude) rats. After 3-6 months, the transplants were evaluated by light and electron microscopy using antibodies against tryosine hydroxylase (TH), human specific Thy-1 (Thy-1), 5-hydroxytryptamine (5-HT), and laminin. In vivo chronoamperometric studies of K+-induced release of electroactive species were done prior to the histochemical evaluations. At the light microscopical level, Thy-1-immunoreactivity was evenly distributed throughout the entire transplants. Thy-1-immunoreactive nerve fibers were observed radiating from the graft into the host striatum. In sections that were double-stained with antibodies against Thy-1 and TH, such nerve fibers contained both markers. Also 5-HT-immunoreactive cells were found in the grafts with processes both in the grafts and radiating into host neuropil. Laminin immunohistochemistry showed an even distribution of capillaries in the graft with less density than in host brain, suggesting immaturity of graft tissue. At the ultrastructural level, TH-immunoreactive axons made symmetric contacts with unlabeled dendritic shafts and dendritic spines within the host brain. A few asymmetric contacts with TH-immunoreactive axons were seen. 5-HT-immunoreactive terminals made both symmetric and asymmetric contacts with unlabeled dendritic shafts and spines. In vivo chronoamperometry using local application of K+ revealed average signals that were lower on the transplanted side than in control striatum. However, close to the grafts significant amounts of the K+-evoked signal amplitudes were as large as 1.3 microM, and the ratio of the reduction to oxidation currents suggested release of a mixture of dopamine and 5-HT. Taken together, this study shows that human fetal mesencephalic tissue pieces survive grafting into nude rats, develop normal vascularization, and express coexistence of TH- and Thy-1-immunoreactivity. Human TH- and 5-HT-immunoreactive nerve fibers form synapses in host striatum and release monoamine neurotransmitters.

Animals↗
PubMed1988

Expression of the beta-nerve growth factor gene in hippocampal neurons.

In situ hybridization with complementary DNA probes for nerve growth factor (NGF) was used to identify cells containing NGF messenger RNA in rat and mouse brain. The most intense labeling occurred in hippocampus, where hybridizing neurons were found in the dentate gyrus and the pyramidal cell layer. The neuronal identity of NGF mRNA-containing cells was further assessed by a loss of NGF-hybridizing mRNA in hippocampal areas where neurons had been destroyed by kainic acid or colchicine. RNA blot analysis also revealed a considerable decrease in the level of NGF mRNA in rat dentate gyrus after a lesion was produced by colchicine. This lesion also caused a decrease in the level of Thy-1 mRNA and an increase in the level of glial fibrillary acidic protein mRNA. Neuronal death was thus associated with the disappearance of NGF mRNA. These results suggest a synthesis of NGF by neurons in the brain and imply that, in hippocampus, NGF influences NGF-sensitive neurons through neuron-to-neuron interactions.

Animals↗
PubMed1988

Intracerebral xenografts of human mesencephalic tissue into athymic rats: immunochemical and in vivo electrochemical studies.

Intracerebral allografts of fetal neurons have been studied in both rodents and nonhuman primates. Such research has been directed towards problems in developmental neurobiology and in animal models of neurological diseases. Whether intracerebrally transplanted human fetal neurons are capable of forming synapses and releasing neurotransmitters are key questions in any application of this approach to human brain development and dysfunction. We studied these questions by examining the immunocytochemical and in vivo electrochemical properties of xenografts of human mesencephalic dopaminergic neurons placed into athymic "nude" rats. The transplanted neurons survive, continue to express human-specific Thy-1 immunoreactivity, and extend neuronal processes into the host brain where morphologically identifiable synapses form. Potassium-evoked release of monoamines occurs in the vicinity of the graft but is absent in more remote areas of the host neuropil. These results indicate that human fetal tissue fragments can provide a source of viable neuroblasts for transplantation. Further, synapses form between pre- and postsynaptic elements expressing different species-specific cell surface markers; thus, these markers do not play a determining role in synaptogenesis.

Animals↗
PubMed1988

Collection and use of aborted central nervous system material. Commendation and controversy.

A recent promising development in the field of central nervous system (CNS) transplantation has suggested the use of human fetal CNS tissue from first trimester abortions for xenografting/explantation. Such experiments would certainly expand our knowledge of the normal developmental mechanisms in human CNS, and allow studies of various indices of maturation and CNS function. However, the suggestion is looked upon with hesitance for ethical, legal and perhaps even for scientific reasons. The initial experiments have been very valuable, though, for our understanding of the structural and functional development of the human CNS, and several legal and ethical concerns have been addressed in working out the procedures for retrieving such tissue. This article tries to put our present knowledge in the right perspective of scientific achievements and potential, legal restrictions and ethical concerns.

Abortion Applicants↗
PubMed1987

Age-related changes in cerebellar noradrenergic pre- and postsynaptic mechanisms: intrinsic vs extrinsic determinants evaluated with brain grafts in oculo.

Intrinsic versus extrinsic determinants of changes in cerebellar noradrenergic transmission during senescence in the rat were measured using homologous cerebellar grafts in oculo. Postsynaptic sensitivity of Purkinje neurons to catecholamines was determined by perfusing the anterior eye chamber with known concentrations of norepinephrine (NE) dissolved in a balanced salt solution. NE elicited a dose-dependent slowing of spontaneous Purkinje neuron discharge in both young (3-6 months) and aged (20-22 months) cerebellar grafts. Hill plots demonstrated that the dose-response relationships in both age-groups were linear and parallel to one another. Aged transplant Purkinje neurons manifested a marked and highly significant subsensitivity to NE with an EC50 of 583 microM, as compared with an EC50 of only 15.9 microM in the young grafts. Young grafts in 15-21-month-old hosts manifested an EC50 of 20 microM for the depressant actions of NE. Collaterals of host iris sympathetic fibers innervate the grafts. Activity of these fibers can be reflexly altered by changing illumination of the retina. The dynamics of presynaptic NE release from these fibers was evaluated using in vivo electrochemistry with Nafion-coated graphite epoxy capillary electrodes, which are highly selective for the monoamine neurotransmitters. As illumination of the ipsilateral retina is increased, the release of catecholamine in the cerebellar graft decreases. A mean change in the extracellular electroactive species of 4.2 +/- 0.6 microM was found in young cerebellar grafts. Equivalent stimuli induced a mean change of 2.3 +/- 0.8 microM in aged grafts. However, this diminished release was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

Transplantation in Parkinson's disease: two cases of adrenal medullary grafts to the putamen.

Autologous adrenal medullary tissue was transplanted unilaterally to the putamen in two patients with severe Parkinson's disease. The first patient exhibited a transient, two-day improvement of motor performance in the limbs contralateral to the implantation site. He also had significantly longer episodes of normal function for about two months. The second patient reported a minor improvement of balance and gait, again lasting for two months. Electrophysiological studies of the motor readiness and auditory evoked potentials were consistent with increased catecholaminergic activity in the basal ganglia after transplantation in both patients. Positron emission tomography showed no postoperative alteration of receptor density in the putamen. No significant adverse effects of the transplantation were observed in the patients' performance on neurological and psychological tests or in their quantitative electroencephalogram and cerebral blood flow recordings. Immediately after the grafting, one patient showed transient signs of sympathetic hyperactivity, probably caused by release of catecholamines from the implanted tissue into the peripheral circulation. We conclude that catecholamine-rich cellular implants in the basal ganglia have transient beneficial effects in patients with severe Parkinson's disease.

Adrenal Medulla↗
PubMed1987

Neurofilament-like and glial fibrillary acidic protein-like immunoreactivities in rat and guinea-pig sympathetic ganglia in situ and after perturbation.

The presence of neurofilament (NF)-like and glial fibrillary acidic protein (GFAP)-like immunoreactivities was studied in sympathetic ganglia of adult rats and guinea pigs during normal conditions and after perturbation. In the superior cervical ganglion (SCG) of normal rats, many ganglion cells and nerve fibers show NF immunoreactivity. Some of these nerve fibers disappear after preganglionic decentralization of SCG; this indicates the presence of a mixture of pre- and postganglionic NF-positive nerves in the ganglion. Cuts in both pre- and postganglionic nerves result in a marked increase in GFAP immunoreactivity in SCG, whereas NF immunoreactivity increases in nerve cell bodies after preganglionic cuts. Only a few ganglion cells show NF immunoreactivity in the normal SCG of guinea pig. All intraganglionic NF-positive nerves are of preganglionic origin; decentralization abolishes NF immunoreactivity in these nerve fibers. The inferior mesenteric ganglion, the hypogastric nerves and colonic nerves in guinea pigs contain large numbers of strongly NF-immunoreactive nerve fibers. When the SCG of adult rat is grafted to the anterior eye chamber of adult rat recipients, both ganglionic cell bodies and nerve fibers, forming on the host iris from the grafted ganglion, are NF-positive. As only the perikarya of these neurons normally exhibit NF immunoreactivity, and the terminal iris arborizations are NF-negative, it appears that the grafting procedure causes NF immunoreactivity to become more widespread in growing SCG neurons.

Animals↗
PubMed1987

Nerve growth factor-like immunoreactivities in rodent salivary glands and testis.

A series of polyclonal affinity-purified antibodies against mouse submandibular-gland nerve growth factor (NGF) are described. Using the submandibular gland of the male mouse and indirect immunofluorescence, the specificity and sensitivity of affinity-purified immunoglobulins and various other fractions from the immunized animals have been tested. It will be shown that affinity-purification schemes, including pre-purification of protein A-fractionated immunoglobulins to remove antibodies that bind to unrelated hydrophilic and hydrophobic proteins, significantly enhance the signal-to-noise ratio and specificity of the antibodies. The antibodies effectively detect NGF-like immunoreactivity in both fresh and fixed glandular tissue. Optimal fixation procedures are described. Fluorescence intensities are linearly correlated to log antibody concentration. By use of the best antibody fractions and optimal fixation protocols, the distribution of NGF-like immunoreactivity is described in eight different salivary glands (rat and mouse, male and female, submandibular and sublingual glands). In addition to the well-known large numbers of immunoreactive cells in the submandibular gland of the male mouse, immunoreactive cells were found in the sublingual gland of male mice and in the submandibular and sublingual glands of female mice. One antibody revealed a weak specific fluorescence also in the submandibular gland of the male mouse. In a survey of genital organs of male mice, one antibody revealed fluorescence in the germ cell line. We conclude that several polyclonal affinity-purified antibodies have been characterized that show a strong NGF-dependent binding to the secretory granules of tubular cells in the submandibular gland of male mice. These antibodies should make it possible to locate endogenous and perturbed NGF levels immunocytochemically, e.g., in the peripheral and central nervous system, where NGF concentrations may be several orders of magnitude lower than in the salivary glands.

Animals↗
PubMed1987

Human fetal tissues grafted to rodent hosts: structural and functional observations of brain, adrenal and heart tissues in oculo.

The potential for growth and development of human tissue grafts was explored by transplantation to the anterior chamber of the eye of rats and mice. Tissues were obtained from therapeutic abortions, performed in the eighth to twelfth week of gestation, using a slight modification of routine vacuum aspirations. Recipients were either adult rats immunosuppressed with cyclosporin A and protected with antibiotics, or nude immunodeficient Balb C mice. Catecholamine-rich tissues such as chromaffin cells from the adrenal medulla, sympathetic ganglia, central dopamine neuroblasts from the substantia nigra, and noradrenaline neuroblasts from the locus coeruleus all survived grafting, and in many cases formed nerve fibers that invaded the host iris. Similarly, central serotonin neurons from developing raphe nuclei grafts were able to innervate host irides. Human fetal cerebellar and cerebral cortical transplants continued their development in rat host eyes. Extracellular recordings from such cerebellar and cortical grafts revealed spontaneously active cells with immature action potential waveforms. Spinal cord grafts also survived and contained substance P-immunoreactive neurons. Dorsal root ganglia were able to form nerve fibers invading the host iris, as evidenced by neurofilament immunohistochemistry. Heart tissue survived and manifested spontaneous rhythmic contractions in oculo. Both human cortex cerebri and heart tissue grafts became innervated by sympathetic adrenergic nerve fibers from the rat host iris. Thus both graft-to-host and host-to-graft neuronal connections may be established between man and rat. Taken together, these data suggest that transplantation of human fetal nervous tissues to the anterior chamber of immunosuppressed or immunodeficient rodent hosts yields a unique model system for studies of human brain development, developmental disturbances, connectivity, and the action of drugs.

Action Potentials↗
PubMed1987

Human fetal cerebellar and cortical tissue transplanted to the anterior eye chamber of athymic rats: electrophysiological and structural studies.

Human fetal tissue fragments from cortex cerebri and cerebellum were grafted to the anterior chamber of the eye of adult athymic nude rats. The grafts were obtained from tissue fragments recovered after elective routine abortions, performed in weeks 8-11 of gestation. Both cerebellar and cortex cerebri grafts survived and developed in the anterior chamber of the eye for 1-4 months. The transplants slowly became vascularized from the host iris. The grafts developed blood vessels with laminin-immunoreactive walls and contained relatively high amounts of glial fibrillary acidic protein- and neurofilament-immunoreactivity in the neuropil after 4 months in oculo. Recordings of extracellular action potentials from the grafts revealed spontaneously active neurons with action-potential waveforms similar to those observed in immature rodents. Morphologically, the grafts showed no signs of rejection. Clusters and bands of large neurons resembling Purkinje cells and dense aggregates of smaller granule-like cells could be found in the cerebellar grafts. Large neurons were also seen in the cortex grafts. Taken together, these data suggest that the athymic rat may serve as a useful tool for studies of central nervous system tissue from otherwise immunologically incompatible species.

Action Potentials↗