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A Seiger

Publications and source records attributed to A Seiger.

At least 163 records · Page 9Linked to original sources

Growth interaction between locus coeruleus and trigeminal ganglion after intraocular double grafting.

Fetal trigeminal ganglia were combined in the anterior chamber of eyes of rat recipients with sequentially grafted fetal locus coeruleus transplants. After maturation of both grafts in oculo the growth pattern of locus coeruleus derived noradrenaline fibres in the iris was examined with Falck-Hillarp fluorescence histochemistry. Contrary to what was expected from earlier studies, which revealed a radiating halo of fibres around the CNS tissue on the iris, the locus coeruleus-derived fibres radiated to a large extent from the adjacent trigeminal ganglion attachment. Thus, the presence of a grafted trigeminal ganglion changed the distribution of the central monoamine nerves growing out in the iris. The possible cause of this changed distribution is discussed. Maturated intraocular trigeminal ganglion transplants were retransplanted, together with the whole iris to which it was attached, into a new eye which already harboured a maturated locus coeruleus graft attached to its host iris. The expected reinitiated locus coeruleus fibre ingrowths into the iris transplants were then compared in those iris transplants that had trigeminal ganglia and controls that had not. The surface area of the iris grafts covered by newly formed locus coeruleus noradrenaline fibres was significantly smaller (27% reduction) if trigeminal ganglia were situated on them during the reinnervation process. This finding strongly supports our earlier studies, which suggested that the presence of sensory nerves in the iris inhibits growth of locus coeruleus in that receptor tissue, and furthermore, that the sensory nerves responsible for this inhibitory interaction have their origin within the trigeminal ganglion itself.

Adrenergic Fibers↗

A system of atypical catecholamine-containing nerve fibres in the rat iris present after total superior cervical ganglionectomy.

A system of hitherto unknown weakly fluorescent fibres was detected in the rat iris by Falck-Hillarp fluorescence histochemistry after superior cervical ganglionectomy. These long smooth winding (SW)-fibres had a scarce and unusual distribution, forming loops and meandering for long distances with limited branching. Pharmacological tests suggest that they store a catecholamine but differ from adrenergic nerves in lacking an efficient uptake mechanism for amines. SW-fibres reached all parts of the iris and gave rise to few scattered extremely faint green fluorescent, limited plexuses of irregularly bulgy fibres. Suggestions as to the cellular origin of the SW-fibres include the ciliary ganglion and the central nervous system.

Animals↗

Opioid peptides excite pyramidal neurons and evoke epileptiform activity in hippocampal transplants in oculo.

The effect of opiate peptide administration on the electrical activity of intraocular hippocampal transplants was studied. Similar to observations in situ, the administration of beta-endorphin or methionine enkephalin produces a concentration-dependent increase in the firing rate of identified pyramidal neurons within hippocampal formation transplants. In addition, these peptides elicit a profound increase in 'EEG' amplitude, which ultimately develops into epileptiform activity. The ability of naloxone to either reverse or prevent the peptide-induced changes in both single unit and EEG activity supports the hypothesis that the excitatory response of the hippocampus to opioid peptides is mediated via an opiate receptor. The results of this study also suggest that the excitatory response to the opiate peptides in hippocampus is the result of alterations in intrinsic neuronal circuitry and is not dependent upon extra-hippocampal afferents.

Animals↗

Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system.

In order to determine if brain tissue grafts can provide functional input to recipient central nervous system tissue, fetal rat dopamine-containg neurons were implanted adjacent to the caudate nucleus of adult recipients whose endogenous dopaminergic input had been destroyed. The grafts showed good survival and axonal outgrowth. Motor abnormalities, which had been induced by the destruction of the endogenous dopaminergic input to the caudate, were significantly reduced after grafting of the fetal brain tissue. These data suggest that such implants may be potentially useful in reversing deficits after circumscribed destruction of brain tissue.

Animals↗

Isolated catecholaminergic projections from substantia nigra and locus coeruleus to caudate, hippocampus and cerebral cortex formed by intraocular sequential double brain grafts.

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.

Animals↗

Seizures and related epileptiform activity in hippocampus transplanted to the anterior chamber of the eye: modulation by cholinergic and adrenergic input.

Transplants of rat hippocampus into the anterior chamber of the eye of a host animal were used to assess the effects of cholinergic and adrenergic neuronal inputs on the generation and duration of seizure activity. Cholinomimetics initiated both seizures and hypersynchronous neuronal activity in the transplants. Cyclic guanosine monophosphate (GMP) derivatives and isobutyl methylxanthine elicited similar changes. Reflex activation of the cholinergic parasympathetic input to the iris and transplant by illumination of the ipsilateral retina also induced seizures or increased the rate of penicillin-induced interictal spike discharge. Application of beta-adrenergic agonists inhibited interictal spikes and paroxysmal depolarizing shifts induced by penicillin. Fluorescence histochemical studies showed that host sympathetic adrenergic fibers derived from the ground plexus of the iris invaded the transplant to form fine varicose nerve terminals. Activation of these adrenergic afferents to the transplant diminished both the amplitude and frequency of penicillin-induced epileptiform activity. Epileptiform activity in hippocampal occular transplants is strongly modulated by cholinergic and adrenergic neuronal inputs, with the former exerting a facilatory influence and the latter, an inhibitory effect.

Adrenergic Fibers↗

NGF and anti-NGF: evidence against effects on fiber growth in locus coeruleus from cultures of perinatal CNS tissues.

The present study examines whether the developing noradrenergic neurons of locus coeruleus depend on endogenous nerve growth factor (NGF) for nerve fiber production and if exogenous NGF stimulates fiber growth in this nucleus, using a collagen gel tissue culture technique. Lucus coeruleus from perinatal rat brain was used in three culture experiments: (1) lucus coeruleus, parietal cerebral cortex, and the superior cervical ganglion, prepared from newborn rats and cultured in different sectors of the same dishes; (2) locus coeruleus and parietal cerebral cortex from 17-day-old rat fetuses cultured in the same manner, and (3) locus coeruleus from 17-day-old rat fetuses co-cultured with spinal, sympathetic and ciliary ganglia from 8-day chick embryos. Experiments 1 and 2 were run with and without addition of NGF and anti-NGF, experiment 3 with and without anti-NGF. Total fiber production in all cultured tissues was evaluated daily by dark field and phase contrast microscopy during 4 days. Adrenergic nerve fiber production was then studied in the same locus coeruleus and superior cervical ganglia from the rats by Falck-Hillarp fluorescence histochemistry. Locus coeruleus and cortex cerebri from fetal rats produced dense fiber halos in culture. Locus coeruleus from newborn rats produced considerably less fibers, newborn cortex only few fibers. Superior cervical ganglia from the same newborn animals produced no or almost no fibers. Addition of NGF was not able to stimulate fiber growth in locus coeruleus nor in cortex cerebri as observed both in the living cultures and by fluorescence microscopy. Likewise, addition of anti-NGF did not affect fiber production in the CNS areas. The negative results with NGF on newborn locus coeruleus and cortex cerebri were in sharp contrast to the strong, highly significant fiber growth response demonstrated by the superior cervical ganglion from the same animals cultured in the same dishes. The third experiment tested whether locus coeruleus in tissue culture contained or produced nerve growth factor or any one of the three chick embryo ganglia. No response whatsoever in these three ganglia was observed. It is concluded that the developing locus coeruleus area does not contain or produce NGF, does not depend on NGF for fiber production, and is not stimulated by exogenous NGF.

Animals↗

Electrophysiological analysis reinnervation of transplants in the anterior chamber of the eye by the autonomic ground plexus of the iris.

Fetal rat hippocampus, cerebellum, and heart were homologously transplanted to the anterior chamber of the eye of adult female recipients. After the grafts were allowed to mature in oculo, ingrowing adrenergic and cholinergic fibers from the iris were activated by changing the illumination of the retina. Electrophysiological recordings from all three types of transplants showed changes similar to those reported for effects of adrenergic and and cholinergic inputs in situ. Pharmacological studies with the transplants indicated that these electrophysiological changes were caused by activation of local muscarinic cholinergic and beta-adrenergic synapses. These data suggest that the intraocular graft is able to induce functional adrenergic and cholinergic inputs from the ground plexus of the iris and support the hypothesis that target organ influences play an important role in synaptogenesis.

Action Potentials↗

Locus coeruleus fibre growth in oculo induced by trigeminotomy.

Locus coeruleus from fetal donors was homologously grafted to the anterior eye chambers of adult rats whose eyes were sympathetically denervated. After intraocular maturation, outgrowth of noradrenaline-containing fibres from the locus coeruleus neurons on the host iris was studied by Falck--Hillarp fluorescence histochemistry. In control animals locus coeruleus grafts produce a halo of noradrenaline-containing nerve fibres around the graft, covering approximately one third of the surface of the host iris. Sensory denervation of host eyes carrying maturated locus coeruleus grafts was produced by intracranial lesions of the trigeminal nerve. Such lesions induced a rapid growth response in the grafted locus coeruleus neurons, leading within three weeks to complete innervation of the host iris. It was concluded that removal of non-sympathetic, non-parasympathetic nerve fibres on the host iris elicits a strong fibre-growth response in the grafted locus coeruleus.

Animals↗

Lead blockade of norepinephrine-induced inhibition of cerebellar Purkinje neurons.

Biochemical studies showing that lead (Pb++) inhibits cerebellar adenylate cyclase (IC50 = 2 micrometer) prompted us to test the effects of this cation on the depression of spontaneous discharge of Purkinje (P) cells produced by iontophoresis of norepinephrine (NE). Previous studies have suggested that the effects of NE on P cell discharge may be mediated by activation of a NE-sensitive adenylate cyclase. Iontophoresis of Pb++ in situ, and in cerebellar transplants in oculo, reliably antagonized NE responses in over 80% of the P cells studied in both preparations. Blockade was readily seen at iontophoretic currents of 5 to 10 nA. Superfusion of PB++ (5--10 micrometer) into the anterior eye chamber also antagonized NE responses in P neurons of the transplant. Spontaneous discharge rate was either unaffected or slightly elevated at Pb++ levels that almost completely blocked NE. Barium, a heavy metal which does not inhibit adenylate cyclase in vitro, did not block NE effects. Stimulation of parallel fibers or iontophoresis of acetylcholine excited P cells. No antagonism was seen, however, between Pb++ and these acetylcholine or parallel fiber excitations. These results raise the possibility that blockade of brain catecholamine receptors may partially underlie the central nervous system toxicity seen with lead administration.

Animals↗

Mnoaminergic reinnervation of the transected spinal cord by homologous fetal brain grafts.

It was shown that immature noradrenaline (NA) containing cells from locus coeruleus and 5-hydroxytryptamine (5-HT) containing cells from the raphé nuclei could survive homologous transplantation to adult spinal cords that were adrenergically denervated by a transverse lesion. Fully viable transplants were found at all postoperative time studied (0.5-4 months) and both NA and 5-HT cell bodies were found to produce a network of nerve terminals in the gray matter and axons in the white matter that reached cranially and caudally at least 10 mm from the cell bodies. The nerve fibers had a normal varicose appearance. It was concluded that NA and 5-HT axons can grow in adult lesioned white matter.

Animals↗

Electrophysiology and cytology of hippocampal formation transplants in the anterior chamber of the eye. I. Intrinsic organization.

Pieces of the immature hippocampal formation were transplanted to the anterior chamber of adult rat eyes. The transplants survived, became vascularized from the host irides, and proliferated extensively in proportion to the age of the donor fetus. These transplants mature and develop an adult organization in oculo. This maturation proceeds unimpaired in the absence of gyrus dentatus or after superior cervical ganglionectomy.

Animals↗