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Biomedical subjects

L Olson

Publications and source records attributed to L Olson.

At least 343 records · Page 19Linked to original sources
PubMed1985

Substantia nigra transplants into denervated striatum of the rat: ultrastructure of graft and host interconnections.

A number of recent experiments suggest that grafted dopaminergic neurons provide functional input to a host caudoputamen which previously had been deprived of its dopaminergic input. The purpose of the present study was to determine whether tyrosine hydroxylase immunoreactive processes which originate in the graft participate in morphologically identifiable synapses in the host neuropil. Prior to transplantation, adult Sprague-Dawley rats received unilateral injections of 6-hydroxydopamine into the medial forebrain bundle. Animals were screened for the success of striatal denervation by a test of apomorphine-induced rotation. Transplants of fetal substantia nigra then were placed into cavities in the caudoputamen. After a 6-8 month survival period, animals were perfused and prepared for tyrosine hydroxylase immunocytochemistry. No evidence of sprouting of the host catecholoaminergic system was observed, even after long survival times. Both pre- and postsynaptic immunoreactive elements were clearly present in the host caudoputamen. Immunoreactive axons made synaptic contact with unlabeled dendrites; immunoreactive dendrites were postsynaptic to unlabeled axon terminals. The present results suggest that both host-to-graft and graft-to-host synapses are present in the host caudoputamen.

Animals↗
PubMed1985

Monoamine release from dopamine-depleted rat caudate nucleus reinnervated by substantia nigra transplants: an in vivo electrochemical study.

Previous studies have shown that fetal substantia nigra (SN) transplanted into a cavity overlying a dopamine (DA)-denervated caudate nucleus can reverse a number of the behavioral abnormalities induced by the denervation. While some histochemical and physiological evidence suggests that this reversal is the result of a functional DA input from the transplant to the host brain, there is little direct evidence for transmitter release from ingrowing graft-derived nerve fibers. In the present work in vivo electrochemistry was used to analyse the magnitude, time course and spatial distribution of neurotransmitter releases evoked by local application of potassium (K+) from DA-depleted, SN transplant-reinnervated striatum. Animals were injected unilaterally with 6-hydroxydopamine (6-OHDA) into the SN and screened by measuring apomorphine-induced rotation. Some were then given SN grafts, which were placed in a 'delayed cavity' just dorsal to the lesioned striatum. Nafion-coated graphite epoxy capillary (GEC) electrodes were employed for the electrochemistry to minimize signals derived from ascorbate or acidic DA metabolites. The GEC electrode was fixed to a K+-filled micropipette and this assembly was used to map the caudate nucleus of control, 6-OHDA-treated, and 6-OHDA-treated, grafted animals. The morphometric relationships between striatal recording sites and transplant location were subsequently verified histologically. Releases from striatal sites within 1.0 mm of the SN grafts were slightly, but not significantly, less than those obtained from control caudate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Nerve fiber production by intraocular adrenal medullary grafts: stimulation by nerve growth factor or sympathetic denervation of the host iris.

This study evaluates the production of adrenergic nerve fibers by adrenal medullary tissue of the adult rat grafted to the anterior chamber of the eye of adult recipients. The chromaffin grafts attach to and become vascularized by the host iris. They decrease in size intraocularly during the first 3 weeks. This decrease is somewhat counteracted by sympathetic denervation of the host iris, and better counteracted by sympathetic denervation and addition of nerve growth factor (NGF, given at grafting and 1 and 2 weeks after grafting). Outgrowth of adrenergic nerve fibers from the grafts into the host iris was studied in wholemount preparations by use of the Falck-Hillarp technique 3 weeks after grafting. The innervated area of the host iris was approximately doubled in the chronically sympathectomized group and doubled again in the chronically sympathectomized NGF-supplemented group. Chronic sympathetic denervation had no effect on density of outgrowing nerves, whereas addition of NGF more than doubled nerve density. Since sympathetic denervation causes a slight elevation of NGF activity in the iris, the present experiments are taken as evidence that the level of NGF in the iris regulates formation of nerve fibers by adrenal medullary tissue grafts from adult rats.

Adrenal Medulla↗
PubMed1985

On the origin and distribution of vasoactive intestinal polypeptide-, peptide HI-, and cholecystokinin-like-immunoreactive nerve fibers in the rat iris.

The presence and distribution of nerve fibers expressing immunoreactivity to the neuropeptides vasoactive intestinal polypeptide, peptide HI and cholecystokinin was examined in stretch-prepared rat iris whole mounts. By use of antiserum to vasoactive intestinal polypeptide an irregular, relatively sparse network of varicose, intensely fluorescent fibers was observed innervating both the dilator plate and the sphincter area. Positive fibers were present also in the ciliary body and the choroid membrane. Surprisingly, a large variation in the amount of vasoactive intestinal polypeptide-positive nerves was seen among irides. Furthermore, an uneven distribution of fluorescent nerve fibers was observed within individual irides. Thus, some areas had a relatively dense innervation, whereas others were devoid of immunoreactive nerve fibers. A similar fiber system was detected using antiserum to peptide HI. In all probability, vasoactive intestinal polypeptide and peptide HI coexist within the same nerve population. A denser and more regular network of cholecystokinin-positive fibers was found in normal rat irides. Such fibers were also present in the sphincter area and in high density in the choroid membrane. Neither extirpation of the superior cervical nor the ciliary ganglion caused any detectable decrease in amount of either vasoactive intestinal polypeptide/peptide HI- or cholecystokinin-positive fibers. However, capsaicin, which in the iris causes permanent disappearance of substance-P fibers, had a similar effect on cholecystokinin-positive fibers, whereas no effect was noted on the vasoactive intestinal polypeptide/peptide HI fiber network.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Combined grafts of the ventral tegmental area and nucleus accumbens in oculo. Histochemical and electrophysiological characterization.

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. Enkephalin-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.

Animals↗
PubMed1985

Chronic implants of chromaffin tissue into the dopamine-denervated striatum. Effects of NGF on graft survival, fiber growth and rotational behavior.

Adult rat chromaffin tissue was transplanted into striatum of adult rat recipients whose nigrostriatal dopamine pathway had been lesioned on the grafted side by 6-hydroxydopamine. Long-term survival of the intrastriatal chromaffin grafts and the effects of treatment with nerve growth factor (NGF) was studied histochemically using Falck-Hillarp fluorescence histochemistry and functionally using rotational behavior induced by apomorphine. Small, cortex-free adrenal chromaffin tissue grafts survived permanently in striatum. The number of surviving cells was significantly increased by NGF. NGF treatment also caused transformation of many cells towards a more neuronal phenotype and greatly enhanced the adrenergic nerve fiber outgrowth into host brain tissue. NGF was either injected stereotaxically into the site of transplantation or infused continuously using implantable osmotic minipumps and a stereotaxically placed chronic indwelling dialysis fiber through striatum. The latter arrangement permitted continuous infusion of NGF for 14-28 days and caused a vigorous adrenergic nerve growth response by the grafts directed towards the source of NGF in the brain. There was a clearcut correlation between morphological signs of taking and rotational behavior. Grafts, and in particular grafts treated with NGF, were able to significantly and permanently counteract the rotational behavior induced by apomorphine. There seemed to be a dose relationship between NGF treatments and amount of reduction of asymmetric behavior. NGF treatment probably decreased the relative importance of diffuse release of catecholamines from chromaffin cells in the graft and increased the importance of adrenergic innervation of host striatum by cells in the graft. Immunofluorescence using antibodies against glial fibrillary acidic protein did not reveal any marked gliosis around the grafts nor were there any marked gliotic reactions around chronic indwelling dialysis fibers. We conclude that implantation of chromaffin tissue into striatum in conjunction with NGF treatments is an effective means of counteracting some of the symptoms of experimentally induced unilateral parkinsonism in rats.

Adrenal Medulla↗
PubMed1985

Spinal cord grafts in oculo: survival, growth, histological organization and electrophysiological characteristics.

Fetal spinal cord tissue was grafted to the anterior chamber of the eye of adult recipients. Transverse segments from the cervical and high thoracic levels were divided in halves which were grafted directly or further divided into ventral horn and dorsal horn parts before grafting. Survival and intraocular growth was monitored through the cornea. Grafts from E14 to E16 grew to final sizes several times the initial size. The final size of E17 grafts was approximately similar to the initial size, while the final size of E18 and E19 grafts was considerably smaller than the size at grafting. All grafts were well vascularized from the host iris. Grafts from younger donors contained several neurons typical of spinal cord including alpha-moto-neuron-type cells. Cells were found in clusters in gray matter areas surrounded by white matter. Extracellular recording revealed many spontaneously active cells. Several had high sustained discharge (10-25 Hz) and large amplitudes. Many cells could be excited by stimulation of the graft surface via activation of local afferents. It is concluded that the capacity of fetal spinal cord tissue to survive grafting to the eye chamber is inversely related to the donor age. Before E17, large grafts retaining several morphological and electrophysiological characteristics of spinal cord are obtained. The intraocular spinal cord graft provides a useful model for studies of spinal cord development and, using co-grafting techniques, a model for spinal cord regeneration and functional connectivity.

Animals↗
PubMed1985

Image analysis of GFA-positive astrocytes from adolescence to senescence.

Smears of fresh rat brain tissue combined with immunohistochemistry using antiserum to glial fibrillary acidic protein (GFA) were used to visualize individual astrocytes in different cortical regions of rats ranging in age from 1 to 30 months. By computerized image analysis, the cell area and the cell perimeter were determined. Using 4-month-old male Sprague-Dawley rats, it was found that GFA-positive astrocytes from cerebellum and hippocampus were significantly larger, both in terms of cell area and cell perimeter, than similar cells from cortex cerebri. The temporal development was carefully followed in smears of the hippocampal formation where a continuous increase in cell size was observed from 1 to 30 months of age. During the first few postnatal months a rapid increase in both cell area and cell perimeter was observed using Sprague-Dawley rats. For studies of senescent animals, Fisher 344 rats specifically bred for aging studies were obtained. Using such animals, a second, highly significant slower growth phase which continued until the longest time points studied was observed. A separate experiment using Sprague-Dawley rats also showed large differences in both cell area and cell perimeter of GFA-positive cerebellum and cortical astrocytes taken from 6-week- and 18-month-old animals. In conclusion, the present study shows that maturation of GFA-positive astrocytes is a process which continues for several months postnatally. This relatively rapid growth phase is followed by a slower increase in cell size, probably continuing throughout life.

Age Factors↗
PubMed1985

Electrophysiological and neurochemical correlates of the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in the mouse.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an agent which produces a parkinsonian syndrome in man. To explore the use of MPTP in a rodent model of parkinsonism, male albino mice (NMRI) were given MPTP (50 mg/kg, s.c.) twice with a 6-8 h interval. Up to 10 weeks after injection, mice were killed and high-pressure liquid chromatography was used to assay dopamine (DA) and noradrenaline (NA) concentrations in various regions of the CNS. At 4 and 10 weeks after injection, DA levels were significantly reduced in occipital cortex (-40%), hippocampus (-30%), and striatum (-60%). NA levels were reduced by 60-80% in frontal and occipital cortex, hippocampus, and cerebellum. Neither DA nor NA concentration was reduced in spinal cord. Dopaminergic denervation was also suggested by electrophysiological data which showed that treatment with MPTP increased the spontaneous discharge rate of caudate neurons and decreased the potency of locally administered phencyclidine, an indirect DA agonist. However, denervation was evidently not complete enough to produce postsynaptic receptor supersensitivity, as MPTP treatment did not increase the potency of locally applied DA, and it did not increase 3H-spiperone binding in striatal membrane preparations. These results suggest that MPTP causes regionally selective and long-term reductions of catecholamine transmission in the CNS of the mouse.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Distribution of Thy-1-like immunoreactivity in normal, sympathetically denervated and grafted mouse irides.

The distribution of Thy-1-like immunoreactivity was studied in whole-mounts of adult mouse iris and intraocular iris grafts 4 days and 4 weeks postoperatively. After fixation in picric acid/paraformaldehyde, the irides were incubated with a polyclonal rabbit anti-mouse brain Thy-1 antibody. In the adult mouse iris, a dense network of thin bundles and individual fibres was seen on the dilator plate and in the sphincter. Fluorescence paucities, resembling Schwann cell nuclei, were frequently seen along the bundles. Numerous mast cells, stained specifically with the Thy-1 antibody, were scattered over the entire surface of the iris. The ciliary body contained several brightly fluorescent bundles, and some circularly running individual fibres. In 4-day iris grafts, the Thy-1-like immunoreactivity had disappeared, except in mast cells. After 4 weeks in oculo, a regular plexus of thin fibres had reappeared in the iris grafts. Sympathetic denervation of adult irides did not seem to affect the Thy-1 immunoreactivity in terms of either fluorescence intensity or fibre distribution. The present data suggest a distribution of the glycoprotein Thy-1 along nerve fibres in the iris.

Animals↗
PubMed1985

Virus-associated deficiencies in the mitogen reactivity in celebes black macaques (Macaca nigra).

Celebes black macaques (Macaca nigra) with a history of diabetes mellitus, recurrent bacterial and protozoal infections, diarrhea, anemia, weight loss, anorexia, and a high mortality were studied to determine their immune status. Two groups of monkeys, healthy and unhealthy, were formed on the basis of a clinical assessment. The proliferative response and the pokeweed-mitogen-induced polyclonal IgG response of peripheral blood mononuclear cells of unhealthy monkeys were significantly less than the responses of healthy monkeys. The percentage of HLA-DR+ cells varied greatly in unhealthy monkeys. The OKT4/OKT8 ratios of unhealthy monkeys were generally greater than the ratios of healthy monkeys. Unhealthy monkeys usually had smaller percentages of OKT8+ cells than did healthy monkeys. The two groups of monkeys were examined for the presence of a syncytial forming retrovirus by a coculture assay involving Raji cells, a human B lymphoblastoid cell line. A type D retrovirus was detected in the unhealthy group but not in the healthy group. Retroperitoneal fibromatosis was detected in several monkeys in the unhealthy group.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Parasympathetic neurotrophic activity in the rat iris: determination after different denervations.

The iris of the adult rat contains one or several neurotrophic factors that enhance the survival of dissociated parasympathetic neurons (from the embryonic chick ciliary ganglion) in culture. To assay survival activity, iris homogenates were serially diluted with culture medium and the percentage of neurons surviving for 2 days in a collagen matrix in culture determined. The extract induced survival curves that were similar for denervated and normal irides. Similarly no differences in fibre outgrowth from cultured whole ciliary ganglia were found. The results suggest that the apparent level of parasympathetic growth factor(s) is not under strict control of the innervation of the iris.

Animals↗
PubMed1985

Reinnervation of dopamine-denervated striatum by substantia nigra transplants: immunohistochemical and electrophysiological correlates.

This study evaluated whether or not fetal substantia nigra tissue, grafted to striatum previously lesioned with 6-hydroxydopamine, provides functional dopaminergic reinnervation of striatum. Falck-Hillarp histochemistry and immunofluorescent staining for tyrosine hydroxylase demonstrated extensive networks of nerve fibers which extended 1-1.5 mm from the nigral grafts into striatal tissue. Multibarrel micropipettes were used to record neurons electrophysiologically and test neuronal responses to phencyclidine which was applied locally by pressure microejection. "Distal" neurons, defined as those striatal neurons more than 2.0 mm from the nigral graft, fired at an average spontaneous rate of 13.4 spikes/s and were relatively insensitive to the effects of locally applied phencyclidine. However, "proximal" neurons, defined as those neurons less than 1.0 mm from nigral grafts, fired at a significantly lower average rate of 4.9 spikes/s, and were significantly more sensitive than distal neurons to the effects of phencyclidine. These results suggest that fetal substantia nigra grafts can provide functionally significant reinnervation of striatum previously lesioned with 6-hydroxydopamine.

Animals↗
PubMed1985

Intraocular grafts of nucleus raphe dorsalis provide cografted spinal cord with a serotonergic innervation.

Nucleus raphe dorsalis was sequentially cografted with spinal cord to the anterior chamber of the eye of adult rats. After maturation in oculo, the double grafts were examined histologically and immunohistologically utilizing an antiserum to serotonin (5HT). No 5HT-like immunoreactivity could be detected in grafts of single spinal cord or in irides of nongrafted eyes. In single raphe grafts, positive cell bodies and a dense terminal plexus were found. 5HT-positive fibers also penetrated into the irides forming dense networks in the walls of blood vessels and elsewhere in the irides. When spinal cord was cografted to maturated nucleus raphe dorsalis grafts, the raphe graft provided the spinal cord graft with a serotonergic innervation. Interestingly, when the grafting procedure was done in reversed order, i.e., the spinal cord was grafted first and left to mature before immature raphe grafts were added to the eye, the average density of 5HT-positive nerve terminals in the spinal cord part was clearly higher. It is concluded that immature as well as mature isolated spinal cord tissue can become innervated by adjacent central 5HT-neurons. Thus isolated replicas of descending serotonergic pathways to the spinal cord, suitable for electrophysiological analysis, are obtained in oculo.

Animals↗
PubMed1985

Neurochemical and histochemical characterization of neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain catecholamine neurones in the mouse.

Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused a rapid and long-lasting reduction of both 3,4-dihydroxyphenylalanine (dopamine, DA) and noradrenaline (NA) in mouse brain, as observed histo- and neurochemically. The depleting effects were more pronounced after repeated MPTP administration and the most marked reductions were observed after 2 X 50 mg MPTP/kg s.c., when DA in striatum and NA in frontal cortex were reduced by greater than 90% 1 week after MPTP. Mice with such catecholamine depletions were markedly sedated and almost completely immobilized. The behavioural syndrome after MPTP resembled that seen after reserpine, a monoamine-depleting drug. MPTP also caused a long-lasting reduction of catecholamine uptake in striatal DA and cortical NA nerve terminals and reduced tyrosine hydroxylase activity in these regions. There was no evidence that MPTP caused any marked DA and NA cell body death. MPTP given acutely transiently elevated serotonin levels. The results are compatible with a neurotoxic action of MPTP on both DA and NA nerve terminals. The nigro-striatal DA and the locus coeruleus NA neurone systems appeared to be most susceptible. Synthesis and utilization of residual striatal DA and cortical NA were increased, as often observed in partially denervated monoamine-innervated brain regions. Both DA and NA showed a gradual recovery, which took months to become complete and may have been related to a regrowth of catecholamine nerve terminals.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Long-term follow-up of canine segmental pancreatic autografts.

The functional and morphologic characteristics of free-draining, pancreatic segmental autografts (FDPS) were studied in 8 beagle dogs that had survived longer than 4 yr. After pancreatectomy, animals received FDPS autografts of the left pancreatic limb, representing approximately one-third of the total pancreas with iliac vessel anastamoses. The grafted recipients were given pancreatic enzyme supplements (Viokase). After transplantation (tx), all 8 animals sustained fasting euglycemia with no evidence of microvascular complications. After 4 yr, IVGTT revealed K-values (%/min) that were not significantly different from age-matched controls (2.9 +/- 0.5 versus 3.7 +/- 0.6, P greater than 0.05). Mean fasting serum insulin levels were significantly greater in the tx animals (49 +/- 5 microU/ml versus 12.2 microU/ml, P less than 0.001), although the incremental response to i.v. glucose (0.5 g/kg) was less than in controls (P less than 0.05). Mean fasting plasma C-peptide levels (0.09 +/- 0.01 pmol/ml versus 0.21 +/- 0.5 pmol/ml) and peak C-peptide responses to i.v. glucose were both significantly less than in controls. Sequential pancreatic biopsies up to 2.5 yr post-tx showed atrophy of the exocrine pancreas with coalescence of islets and mild fibrosis that did not progress with time. Immunoperoxidase stains confirmed the presence of insulin, glucagon, and somatostatin within nests of islet cells. Four years after transplantation of FDPS autografts in pancreatectomized dogs, excellent function is retained. The consequences of peripheral hyperinsulinemia remain to be determined.

Animals↗