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  • 1
    ISSN: 1432-0568
    Keywords: Human brain ; Prenatal ontogeny ; Monoamine neurons ; Fluorescence histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of monoamine neurons in the human fetal brain was studied by Falck-Hillarp fluorescence histochemistry. Catecholamine (CA)- and 5-hydroxytryptamine (5-HT)-neuron systems were found in the smallest brain studied, obtained from an embryo having a total length of 2.1 cm and a gestational age of 7 weeks. A marked proliferation and differentiation of the monoamine neuron systems took place between the 7th and 23rd week of gestation (the range covered in the present investigation) permitting a mapping of major cell groups, as well as several axon pathways and terminal innervation patterns. The basic cytoarchitectonic features of the central monoamine neurons in human fetuses were strikingly similar to those of the fetal rat. Thus, a large complex of cell bodies was found in the developing substantia nigra area, in all probability the CA neurons of the nigro-striatal dopamine system. Axons projected towards the corpus striatum. Here, the putamen and, somewhat later, the caudate nucleus became richly innervated by CA nerve terminals. Small clusters of CA nerve cells were found in the hypothalamus, e. g. in the ventral periventricular area. 5-hydroxytryptamine nerve cell bodies were distributed throughout the raphe areas from the medulla oblongata to the mesencephalon forming several well delineated groups, e.g. a large group in the area of nuc. raphe dorsalis. 5-HT axons projected caudally in the ventral parts of the medulla oblongata and into the spinal cord and rostrally through the mesencephalon and into the forebrain. CA cell bodies were also found in several large complexes of the medulla oblongata and pons, where such cell bodies are of the noradrenaline type in animals. The principal locus coeruleus consisted of densely packed fluorescent cells and several loosely packed groups extended laterally, medially, dorsally and rostrally from this area. Several axon bundles ascended dorsally from this complex. Ventrally and dorsally located CA cell groups were found in the medulla oblongata, and green fluorescent axons descended into the spinal cord. Varicose nerve terminals of the CA type were found, e.g. in the spinal cord, around the third ventricle and, using brain smears, also in the developing cerebral and cerebellar cortices. There seemed to be an outflow of CA axons in ventral nerve roots of cranial and spinal nerves. The developing pineal gland showed scattered 5-HT-containing parenchymal cells. Area postrema contained a number of strongly fluorescent CA cells and some weaker fluorescent 5-HT cells.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1106
    Keywords: Human brain development ; Xenografts ; Monoamine neurons ; Cerebellum ; Cortex cerebri ; Adrenal medulla ; Ganglia ; Heart ; Intraocular transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1106
    Keywords: Brain transplants ; Catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sequential intraocular grafting of defined areas from fetal rat brain to adult host rats was used to explore the possibility that such double grafts would become interconnected. Norepinephrine- containing neurons of the locus coeruleus were grafted together with either parietal cerebral cortex, hippocampus, or the caudate nucleus. Dopamine-containing neurons of the substantia nigra were transplanted together with either parietal cerebral cortex or the caudate nucleus. The brainstem grafts showed good survival and development in oculo, using both histochemical and electrophysiological criteria. Locus coeruleus neurons were found to innervate cerebral cortex, hippocampus, and the caudate nucleus. Substantia nigra neurons invaded cerebral cortex abundantly, with a terminal distribution typical of cortical DA terminals in situ. The innervation of the caudate nucleus from substantia nigra transplants was variable, but areas of dense confluent terminals were observed. We conclude that sequential brain grafting in oculo permits generation of isolated yet defined catecholaminergic projections, which are suitable for electrophysiological, pharmacological, and histochemical studies.
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  • 4
    Electronic Resource
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    Springer
    Experimental brain research 29 (1977), S. 15-44 
    ISSN: 1432-1106
    Keywords: Intraocular sequential transplantations ; Central monoamine neurons ; Reinitiated nerve growth ; Heterologic innervation ; Fluorescence histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Grafts of central monoamine (MA) neurons and irides were combined in the rat anterior eye chamber to reveal factors regulating nerve fiber growth. Central MA nerve fiber production in host irides and iris grafts was measured by quantitative Falck-Hillarp histochemistry and 3H-metaraminol uptake in sympathetically denervated eyes. 1. Fetal locus coeruleus (LC) grafts produce a dense halo of noradrenaline (NA) fibers on host irides. When this growth ceases after 6 weeks, it covers only 1/3 of the host iris, despite the sympathetic denervation. If an iris graft is then placed in contact with the LC graft, the new iris will reinitiate a vigorous fiber growth in the central NA neurons leading to a rapid and complete reinnervation of the iris graft. There is no simultaneous increase in the halo of nerve fibers on the host iris, showing that this growth response is highly selective. The innervation of the iris grafts and host irides remain essentially unchanged during 1 year without degenerative signs. Grafted dopamine and 5-hydroxytryptamine neurons show a similar response to iris grafts. 2. Addition of a second iris graft, sandwiched on top of the first iris graft which in turn was attached to a LC graft results in complete reinnervation also of the second iris graft. Hence, maturated NA neurons are capable of repeated fiber growth responses and contact between the stimulus (second iris graft) and the stimulated neurons can be indirect (via the first iris graft). 3. Immature LC grafts are also stimulated to additional growth by iris grafts present during ontogenetic maturation of LC in oculo. 4. When iris grafts are placed opposite to LC on the host irides and without contact with the fiber halo on the host irides, there is no LC fiber growth stimulation. 5. When iris grafts are placed in sympathetically denervated eyes first, and fetal LC grafts added to them after 1 month the pattern of NA fibers in the iris grafts becomes similar to that in host irides, i.e. only a halo of fibers around the CNS graft. The growth stimulation exerted by acute iris grafts ceases with time of the iris graft in oculo. 6. Mature intact NA neurons of LC attached to its host iris can survive regrafting to a new eye. The distribution of fibers from the surviving neurons on the old host iris changes from a halo to a wide spread pattern. It is concluded that iris grafts exert a powerful growth stimulus on intraocular MA neurons and become fully innervated in contrast to the host irides. Iris grafts differ from host irides by being initially ischemic and completely denervated. It may be that the acute removal of one or several non-adrenergic nerve fiber types normally present in the iris triggers the growth response.
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  • 5
    ISSN: 1432-1106
    Keywords: Brain grafts ; Noradrenergic input
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Following sequential intraocular transplantations of areas containing NE cell bodies (locus coeruleus or superior cervical ganglion) and of NE fiber target areas (hippocampus), both pieces mature in a manner analogous to that observed for individual transplants. NE-containing nerve fibers, derived from either LC or SCG transplants, can be seen to invade the hippocampal formation. When LC is used, the invading fibers markedly hyperinnervate the hippocampus while SCG-derived fiber densities approximate those seen with innervation from the adrenergic ground plexus of the iris. Electrophysiological recordings from neurons in the LC reveal an atropine-sensitive excitatory response to illumination, suggesting innervation of the LC by cholinergic nerve fibers from the iris. This is supported by the fact that dense cholinesterase-positive staining can be found in the LC piece. Application of an epileptogenic agent, such as penicillin, results in a marked excitation of neurons in the LC without inducing epileptiform activity in the hippocampus. In contrast, single hippocampal grafts seize readily after penicillin. Local application of the inhibitory agent GABA into the LC allows penicillin-induced epileptiform activity to generate in the hippocampus, suggesting that functional inhibitory innervation develops between NE fibers derived from LC and pyramidal neurons in the hippocampus. Supporting this, subsequent excitation of LC neurons by iontophoresis of glutamate terminates the hippocampal seizure. Prior administration of reserpine (2.5 mg/kg) disrupts the inhibitory influence of LC innervation on the hippocampal EEG following penicillin. After reserpine, the hippocampal portions of double grafts behave like single hippocampal transplants. It is concluded that sequential transplantations of cell body and target regions of the CNS to the anterior chamber of the eye creates a functional, yet isolated, neuronal pathway which can be utilized to study the development of neuronal connections.
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  • 6
    ISSN: 1432-1106
    Keywords: VTA-accumbens grafts ; Dopamine neurons ; Enkephalin ; CCK ; Electrophysiology ; Intraocular brain transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dissection techniques and optimal donor stages have been established for constructing an isolated intraocular model of the ventral tegmental area (VTA)-accumbens system using intraocular sequential grafting. Single grafts including accumbens and VTA respectively survived and developed many organotypic features when taken from 15–17 day fetuses. Falck-Hillarp fluorescence histochemistry showed dopamine neurons and terminals in single VTA grafts, no or almost no catecholamine fibers in single accumbens grafts, and a well-developed VTA-accumbens dopamine pathway in combined grafts where cell bodies in the VTA part provided the accumbens part with a rich terminal network. A similar distribution was found using immunohistochemistry with antibodies directed against tyrosine hydroxylase. CCK-like immunoreactivity had a distribution that mimicked that of the catecholamine-containing system. Enkephaline-like immunoreactivity was found both in single VTA and in single accumbens pieces as well as in both parts of the double grafts. Cells with long-duration action potentials typical of dopamine neurons discharged at approximately 8 Hz in single VTA grafts and below 1 Hz in the VTA part of VTA-accumbens double grafts. Cells in the accumbens portion of double grafts had shorter action potential durations and fired at 10–20 Hz. Haloperidol increased discharge frequency in VTA neurons with long action potential durations while apomorphine reduced discharge markedly. Antidromic activation of putative dopamine neurons in the VTA part was obtained by electrical stimulation of the accumbens part. The indirect dopamine agonist + 3-methyl-phencyclidine slowed firing rates of neurons in the accumbens part of double grafts. Taken together, the histochemical and the electrophysiological data show that the intraocular VTA-accumbens system retains several of its normal structural and functional characteristics. It is proposed that the isolated VTA-accumbens projection can be used as a model to study the cellular mechanism of action of stimulant and opiate drugs of abuse.
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  • 7
    ISSN: 1432-1106
    Keywords: Brain grafts ; Noradrenergic fibers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The developing hippocampal anlage of rats was homologously grafted to the anterior chamber of the eye of adult recipients. After intraocular maturation of the hippocampal graft and removal of the sympathetic innervation of the eye by ipsilateral superior cervical ganglionectomy, four types of monoamine neurons were transplanted to the eye chamber: Peripheral sympathetic neurons, central adrenergic neurons of locus coeruleus, central dopaminergic neurons of substantia nigra, and central 5-hydroxytryptamine neurons of the lower raphé nuclei. All four classes of monoamine neurons were able to reinnervate the hippocampal graft, but the fiber ingrowth differed markedly. Although peripheral sympathetic neurons produced a pattern of adrenergic innervation in the hippocampal graft which resembled innervation of the hippocampus by the locus coeruleus in the brain, locus coeruleus neurons themselves produced an extremely dense plexus of fibers within the graft. This hyperinnervation remained intact for up to 9 months, the longest period of time studied. The locus coeruleus graft itself received fibers from the hippocampus graft, as demonstrated by the retrograde transport of horseradish peroxidase. We conclude that the hippocampal graft exerts a much stronger growth stimulation on the locus coeruleus neurons than on the peripheral sympathetic neurons. The difference between innervation patterns suggest that both presynaptic and postsynaptic influences determine fiber ingrowth in the central nervous system.
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  • 8
    ISSN: 1432-1106
    Keywords: Brain transplants ; Area dentata ; Noradrenergic hyperinnervation ; Inhibited axonal growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In situ area dentata receives a sparse noradrenergic innervation from locus coeruleus. Embryonic area dentata co-transplanted with locus coeruleus to the anterior eye chamber receives an abundant ingrowth of nerves from the noradrenergic neurons of the locus graft. We sought to identify restrictive forces acting on coeruleo-dentate axons by arranging for the innervation of area dentata transplants by either entorhinal cortex or septal nuclei transplants prior to locus coeruleus transplantation. The noradrenergic hyperinnervation was not inhibited when locus coeruleus transplants were placed on the opposite side of area dentata from the entorhinal or septal transplant. Noradrenergic innervation of area dentata was restricted when the locus coeruleus transplant was placed in contact with the septal transplant. This inhibitory interaction seemed to take place between the septal and locus coeruleus transplants rather than in the area dentata neuropil. This type of interaction points towards one means by which axonal growth may be inhibited during development or in the adult.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0920-9964
    Keywords: (Schizophrenia) ; Brain derived neurotrophic factor ; Cholinergic receptors ; Growth factors ; Neuronal development
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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