Biomedical subjects

L Olson

Publications and source records attributed to L Olson.

At least 361 records · Page 20Linked to original sources

PubMed1985

Appearance of the noradrenergic markers tyrosine hydroxylase and neuropeptide Y in cholinergic nerves of the iris following sympathectomy.

Selective autonomic denervations of the iris have been used to study the possible redistribution of adrenergic markers within adult nerve fiber systems and to reveal the cellular origin of a nonsympathetic fiber plexus induced to express such markers. The presence and distribution of fibers showing neuropeptide Y (NPY)- and tyrosine hydroxylase (TH)-like immunoreactivity was studied in the rat iris using stretch-prepared whole mounts. Normal irides contained a dense regular network of NPY-positive varicose fibers. Such fibers were regularly seen innervating blood vessels. The choroid membrane had a high number of fluorescent fibers. A similar, although slightly denser TH-positive fiber system was visualized in the iris. One or 2 days after surgical removal of the superior cervical ganglion, almost all NPY- and TH-positive fibers had disappeared, suggesting that most, if not all, NPY-positive fibers in the iris originate in the superior cervical ganglion. In irides from long-term sympathectomized animals, a high number of TH- and NPY-immunoreactive fibers had reappeared, while such irides were devoid of catecholamine-containing fibers, as evidenced by Falck-Hillarp histochemistry. The appearance of TH- and NPY-positive fibers in sympathetically denervated irides was clearly time dependent. The distribution of fluorescent fibers in irides from intact and sympathectomized animals showed obvious dissimilarities such as a lower fluorescence intensity and fewer varicose fibers in denervated irides. Furthermore, in irides from sympathectomized rats, TH- and NPY-positive fibers were not associated with blood vessels. Unilateral removal of the parasympathetic ciliary ganglion, which supplies the iris with cholinergic fibers, 3 days prior to sacrifice in animals bilaterally sympathectomized 1 month earlier, led to a drastic reduction in numbers of TH- and NPY-positive iris fibers on the ciliarectomized/sympathectomized side as compared to the sympathectomized-alone side. The present experiments thus suggest that adult cholinergic neurons in vivo are capable of expressing adrenergic characteristics under experimental conditions.

Adrenergic Fibers↗

PubMed1985

Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse: an in vivo electrochemical study.

The long-term (i.e., 4-5 months) effects of large doses (3 X 50 mg/kg) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal dopamine-containing afferents were studied in the NMRI strain of mice. Recently improved in vivo electrochemical methods were first used to examine the magnitude, spatial distribution and temporal dynamics of monoamine release initiated via local application of potassium in various regions of the mouse striatum. Immunohistochemical localization of tyrosine hydroxylase and computer-based image analysis were also used to quantitate regional catecholamine-containing nerve fiber densities in the caudate nucleus. The in vivo electrochemical studies showed a statistically significant decrease in the average potassium-evoked release of electroactive species from the MPTP-treated mouse caudate nucleus vs. control. Greater decreases in release were seen in dorsal than in ventral striatum (55% vs. 33%). The average rise time of potassium-evoked release was also significantly prolonged (greater than 50%) after MPTP pretreatment. Histochemical studies showed an overall reduction in the density of dopamine-containing terminals in the drug-treated mice, with a greater loss observed in the more dorsal regions of the caudate nucleus. The experimental data thus support a long-term selective destruction of dorsal vs. ventral dopamine-containing afferents to the striatum by the neurotoxin MPTP in mice.

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

PubMed1984

Adrenergic transmission in hippocampus-locus coeruleus double grafts in oculo: demonstration by in vivo electrochemical detection.

In vivo electrochemical detection was used to study transmitter release from a synaptically or pharmacologically stimulated noradrenergic isolated pathway formed by double in oculo brain tissue grafts. Retinal illumination, which activates cholinergic nerve fibers that grow into intraocular grafts from the autonomic ground plexus of the iris, produced increases in the concentration of electroactive species in the hippocampal portion of intraocular locus coeruleus-hippocampus double grafts. This response was potentiated after cholinesterase inhibition, and mimicked by perfusion of carbachol, a muscarinic agonist. Much smaller increases in the electroactive species were measured in reserpinized animals, and this minimal response was completely eliminated by the subsequent inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine. Taken together, the data suggest that synaptically released transmitter in these isolated brain circuits can be measured using in vivo electrochemical detection techniques, and lend further support to the hypothesis that in oculo locus coeruleus grafts develop a functional catecholaminergic input to sequentially grafted hippocampus.

Animals↗

PubMed1984

Regulation of axonal ingrowth into area dentata as studied by sequential, double intraocular brain tissue transplantation.

The anterior eye chamber was used as a model environment to study, in isolation, the interaction of embryonic area dentata transplants with transplants of one of three important sources of in situ innervation: entorhinal cortex, locus coeruleus or septal nuclei. None of these brain regions significantly affected the morphogenesis or in oculo growth of area dentata transplants. All three brain regions innervated the area dentata transplant. Entorhinal cortical transplants sent nerve fibers into a limited, and apparently specific, region of area dentata that was adjacent to the entorhinal transplant. This light innervation contrasts to the predominant innervation of area dentata by entorhinal cortex in situ. The fluorescent, noradrenergic neurons of locus coeruleus provided the area dentata transplant with an abundance of fine varicose nerve fibers. Given about 100 noradrenergic neurons in the locus coeruleus transplant and 4 to 6 months joint survival, the area dentata transplant was noradrenergically hyperinnervated. The cholinergic neurons of the septal nuclei transplant had a prolific ingrowth of acetylcholinesterase (AChE)-positive nerve fibers to the area dentata transplant. There appeared to be a mutual exclusion between the extrinsic AChE-positive fibers and the intrinsic Timm's-positive granule cell mossy fibers in the area dentata transplant. We conclude that isolated replicas of the coeruleo-, septo-, and entorhinal cortico-dentate pathways can be made through sequential intraocular double grafting. The nature of the in oculo connectivity between these replicates offers clues as to the mechanisms that might account for the regulation of nerve growth.

Animals↗

PubMed1984

Intraocular grafting of cultured brain tissue: growth, vascularization and neuron survival in locus coeruleus and cortex cerebri.

Locus coeruleus and cortex cerebri from embryonic (ED 17) and newborn rats were kept 4 days in tissue culture under conditions maintaining organotypic features and then transplanted to the anterior chamber of the eye of adult rats. Vascularization from the host iris was delayed in pre-cultured grafts as compared to directly grafted material. In spite of this, several morphological parameters developed normally. Thus, pre-cultured grafts grew considerably in oculo. Falck-Hillarp histochemistry showed that grafts of cortex cerebri received an adrenergic innervation from the host iris and that locus coeruleus grafts contained central adrenergic neurons capable of innervating a sympathetically denervated host iris. The successful combination of tissue culture and intraocular transplantation should permit the selective advantages of both techniques to be applied to the same tissue pieces, generating new information unobtainable by either method alone.

Animals↗

PubMed1984

Adrenal medullary implants in the dopamine-denervated rat striatum. I. Acute catecholamine levels in grafts and host caudate as determined by HPLC-electrochemistry and fluorescence histochemical image analysis.

Rats with unilateral 6-hydroxydopamine-induced degeneration of the left nigrostriatal dopamine system were given intrastriatal implants of one cortex-free adrenal medulla divided into 4 pieces. Two pieces were placed in the center of the anterior part of the denervated caudate and two pieces in a more posterior position in lateral caudate. The distribution of catecholamines (CA) in grafts and host brain was studied 2, 100 and 400 min after grafting by HPLC-electrochemistry and Falck-Hillarp fluorescence histochemistry combined with computer-aided image analysis. Two minutes after implantation the chromaffin tissue grafts contained large amounts of adrenaline (A) and noradrenaline (NA) and small amounts of dopamine (DA). The chromaffin cells had a relatively normal fluorescence histochemical appearance. From the grafts, CA had spread into the surrounding host brain tissue where high levels of A and NA and low levels of DA were now found in the denervated host striatum. Fluorescence histochemistry and image analysis showed the CA to have spread 1-1.5 mm in all directions from the grafts. The CA concentrations decreased almost linearly with increasing distance from the grafts. At 100 min after implantation approximately a third of the chromaffin cells were still strongly fluorescent while the rest of the cells were very weakly fluorescent or non-fluorescent. The amounts of A, NA and DA in the host brain had decreased considerably, while the size of the fluorescent halo around the grafts had not diminished. At 400 min after grafting, only scattered cells in the chromaffin implants were strongly fluorescent and the surrounding host striatum contained low amounts of CA. It is concluded that intrastriatal adrenal medullary implants acutely release or leak large amounts of CA into surrounding host brain tissue. Taken together with results from the accompanying paper these data show that the grafts can maintain CA levels in host striatum high enough to elicit strong rotational responses during approximately 200 min.

Adrenal Medulla↗

PubMed1984

Adrenal medullary implants in the dopamine-denervated rat striatum. II. Acute behavior as a function of graft amount and location and its modulation by neuroleptics.

Rotational behavior was studied in rats with unilateral 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine system, following intrastriatal grafting of pieces of the adrenal medulla or nervus opticus. The rats were placed in rotometers immediately after the operation. No rotational response was seen in animals implanted with nervus opticus. Rats that received one whole adrenal medullary gland, divided into 4 pieces, showed a strong rotational response with a peak after 100 min and a duration of 400 min. Adrenal medulla-induced rotations were dose-dependent: when rats were grafted with 2, 4 or 8 pieces (where 4 pieces equals one whole adrenal medulla) into 2 sites, 2 pieces induced about half the amount of rotation as 4 pieces, while 8 pieces caused a higher total number of rotations with the 100 min peak approximately doubled compared with rats that had received 4 pieces. The coordinates for the implantation site were also important determinants of the rotational behavior: 4 implantation sites were tested and it was shown that the most central site in the caudate caused the highest total amount of rotations. The rotational behavior could be blocked in a dose-dependent manner by the dopamine-receptor antagonists haloperidol and cis-flupenthixol given immediately after grafting. It is concluded that implantation of chromaffin tissue from the adrenal medulla into the unilaterally 6-hydroxydopamine-denervated striatum causes highly reproducible acute rotational responses that vary with the amount and location of the implanted tissue and that can be blocked by neuroleptics. Thus the experiments permit screening of areas within neostriatum that produce different rotational responses to chromaffin implants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

PubMed1984

Neurotoxicity of the meperidine analogue N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain catecholamine neurons in the mouse.

The effect of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) on central monoamine neurons in mice was investigated using histo- and biochemical techniques. NMPTP (2 X 10 mg/kg i.v.) produced a rapid and long-lasting reduction (-30%) of striatal dopamine, while the dopamine levels were only transiently reduced in mesencephalon and frontal cortex. HVA and DOPAC were initially markedly reduced (-50 to -70%) in striatum while a marked recovery was found in the chronic stage. NMPTP also induced a long-term reduction of noradrenaline in striatum and frontal cortex while 5-hydroxytryptamine and 5-HIAA levels were essentially unaltered. The data indicate a neurotoxic action of NMPTP on both dopamine and noradrenaline nerve terminals in mouse brain.

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

PubMed1984

Degree of hyperinnervation of area dentata by locus coeruleus in the presence of septum or entorhinal cortex as studied by sequential intraocular triple transplantation.

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.

Animals↗

PubMed1984

Intracranial cerebellar grafts: intermediate filament immunohistochemistry and electrophysiology.

Pieces of the developing cerebellar anlage were prepared from 13-15 day old rat embryos and transplanted to the cerebellar region of 5-7 and 13-14 day old rat pups. Approximately two months later, sections showed most grafts to consist of both cerebellar cortex, with a typical trilaminar organization, and white matter areas containing large neuronal perikarya. The astrocytic populations were studied using immunohistochemistry with antisera raised against the intermediate filaments, glial fibrillary acidic protein (GFA), and vimentin. The GFA-antiserum revealed a glial interface along most of the border between host brain and graft. Both antisera stained long, slender, although slightly distorted Bergmann fibers spanning the molecular layer. Using GFA-antiserum, star-shaped fluorescent astrocytes were seen in the granular layer and in the white matter. Only in the white matter did the amount of GFA-like immunoreactivity suggest an astrocytic gliosis. With vimentin antiserum fluorescent astrocytes in the white matter were seen. There were no signs of increased amounts of vimentin-like immunoreactivity. Taken together, the amount and distribution of GFA- and vimentin-like immunoreactivity suggests a rather normal astrocytic development in the cerebellar grafts. Using an antiserum against the neurofilament (NF) triplet, delicate immunoreactive fibres were seen in both the molecular and the granular layer. No positive cell bodies could be visualized in the cortical areas. Although the Purkinje cells themselves were negative, fibre baskets around them were intensely stained. In the white matter a high density of NF-positive fibres and some positive perikarya were visualized. Thus the distribution of NF-like immunoreactivity in the grafts corresponded well to the normal NF distribution. The functional maturation of the cerebellar grafts was studied electrophysiologically. A spontaneous mean discharge rate of 19.3 + 1.7 Hz was recorded from the Purkinje cells. This compares with a discharge rate of 26.8 + 1.0 Hz for Purkinje neurons in situ. The difference was at least partly ascribable to the absence of climbing fibre bursts in the grafts. Local stimulation of the graft surface caused both decreased and increased Purkinje cell discharge. In conclusion, these experiments suggest that grafts of fetal cerebellar buds to the young cerebellum develop into cerebellar tissue having both morphological and electrophysiological characteristics quite similar to the normal cerebellum.

Animals↗

PubMed1984

Enkephalin immunoreactivity in iris nerves: distribution in normal and grafted irides, persistence and enhanced fluorescence after denervations.

The morphology and distribution of nerve fibers showing enkephalin-like immunoreactivity was studied in rat and mouse iris whole mounts. In adult rat, a relatively dense network of varicose fibers was seen throughout the iris. Individual, long, usually smooth fibers were observed running together with non-fluorescent fibers in bundles. Positive nerve fibers were also seen in the ciliary body and the choroid membrane. The fluorescence intensity was normally low. No enkephalin-positive fibers were detected in adult mouse iris. Extirpation or lesioning either one or all the three ganglia known to supply the rat iris with nerve fibers, the superior cervical, the ciliary and the trigeminal ganglia, caused no detectable decrease in amount of enkephalin-positive fibers. However, in irides grafted to the anterior eye chamber of adult recipients, no enkephalin-positive fibers could be observed 2-12 days postoperatively, strongly suggesting that degeneration of these fibers had occurred. When iris grafts were left longer in the eye, nerve fibers with enkephalin-like immunoreactivity reappeared. An increased fluorescence intensity was observed both in the ipsilateral and contralateral iris following extirpation or lesioning all three ganglia and in the ipsilateral iris after extirpation of the ciliary ganglion. Three days after a systemic injection of capsaicin, which causes a permanent disappearance of substance P fibers, the same phenomenon was often observed. This raises the possibility of an interaction between the enkephalin-positive and the substance P fiber systems in the iris.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Chlorhexidine-induced degeneration of adrenergic nerves.

Possible toxic effects of chlorhexidine (CHX) on the sympathetic adrenergic ground plexus were studied in whole mounts of albino rat irides using Falck-Hillarp fluorescence histochemistry. CHX dissolved in an isotone , buffered sodium-acetate solution or in 70% alcohol was injected into the anterior chamber of eye. CHX caused a marked and dose-dependent degeneration of adrenergic nerves. Two days after the lowest dose, 0,25 micrograms (5 microliters of a 0.05% CHX solution), approximately 30% of the nerves had disappeared. Almost complete degeneration was observed after the same time with higher doses (2.5 micrograms, 5.0 micrograms, and 7.5 micrograms corresponding to 0.5, 1.0, and 1.5% CHX respectively). Two weeks after the lowest dose, the nerves had regenerated almost completely. With the highest dose used, only some 40% of the normal adrenergic nerve plexus had reformed after 51 days. Alcohol as a solvent did not have an additive effect on the neurotoxic action caused by CHX. The results demonstrate yet another aspect of chlorhexidine neurotoxicity, degeneration of peripheral adrenergic nerve terminals. This suggests that neurotoxic actions on thin unmyelinated fiber systems should be looked for also in the central nervous system (CNS).

Animals↗

PubMed1984

Neonatal cerebellectomy alters ethanol-induced sleep time of short sleep but not long sleep mice.

The effects of neonatal cerebellectomy on ethanol-induced sleep times in long sleep (LS) and short sleep (SS) mice were investigated. Cerebellectomy did not alter the ethanol sensitivity of LS animals for loss of righting reflex. In contrast, SS mice became more sensitive to alcohol after cerebellectomy. Even so, large differences were still observed between the alcohol-induced sleep times of cerebellectomized LS and SS mice. The data indicate that, while the cerebellum must have a prominant influence on alcohol sleep time in SS animals, this brain structure is not solely responsible for the observed differences in righting reflex sensitivity to ethanol in these two mouse lines. We postulate the existence of noncerebellar central neurons with differential sensitivities to the depressant effects of ethanol in LS and SS mice.

Animals↗

PubMed1984

Chronic lead exposure of the developing brain: electrophysiological abnormalities of cerebellar Purkinje neurons.

This manuscript reviews our recent research concerning electrophysiological effects of chronic low-level lead exposure on developing brain. We found that, although growth, survival and histological organization of in oculo cerebellar grafts appear normal after perinatal exposure to blood lead levels of 450 to 550 micrograms/liter, the physiological activity of Purkinje neurons in these lead-treated grafts is abnormally low after discontinuation of lead treatment. On the other hand, chronic low-level lead exposure postnatally via systemic injections or perinatally via the drinking water did not alter in situ cerebellar Purkinje cell activity. Moderate systemic doses (2 mg/kg) did cause a persistent slowing of Purkinje neuron firing rates; however, this effect was much smaller than in intraocular cerebellar grafts. The slowing may be mediated by lead actions on various transmitter systems. We have found that chronic lead induces catecholaminergic neurons to hyperinnervate target areas. Perhaps this hyperinnervation is initiated by the postsynaptic lead-induced blockade of the electrophysiological effects of norepinephrine which we have previously observed in the cerebellum in situ and in cerebellar grafts in oculo.

Action Potentials↗

PubMed1984

Glial fibrillary acidic protein-like immunoreactivity in the iris: development, distribution, and reactive changes following transplantation.

Using immunohistochemistry with antisera raised against the glial fibrillary acidic protein (GFA), we have studied the appearance and distribution of GFA-like immunoreactivity in whole mounts of rodent iris and in sectioned cat and cow iris. In the adult rat iris, a dense plexus of GFA-positive fibers was seen in both the dilator plate and the sphincter. The fluorescent fibers formed large meandering bundles and a dense irregular network of thinner fibers. In the sphincter, mainly thinner fibers were seen. Thin fibers were also seen winding around blood vessels in the dilator plate. In adult mouse iris, the GFA-positive fibers had a quite different distribution with a few radially oriented fiber bundles superimposed on a more regular network of thinner fibers. Adult guinea pig irides showed still another pattern of GFA-positive fibers with a low number of bundles and thinner fibers forming a sparse irregular network. In thicker fiber bundles of all three rodent species, as well as at branching sites of the thinner fibers, negative or weakly fluorescent swellings surrounded by GFA-like immunoreactivity were present. These structures probably represent the cellular origin of the GFA-positive fibers. Thick, strongly fluorescent fiber bundles, as well as numerous thinner fibers, were seen in sections of cat and cow iris. Prenatally, fibers were visualized at embryonic day 18 in the rat. In these irides as well as in irides from 21-day-old embryos and 1-day-old pups, most fibers were organized in a gradually increasing system of thin meandering fiber bundles that showed limited branching. At postnatal day 6, a more mature network of thinner fibers had developed between the now more numerous fiber bundles. No obvious increase or decrease in the amount of GFA-positive fibers was seen in irides grafted to the anterior eye chamber of adult rat recipients examined 1 and 6 days after grafting. However, in these irides, as well as in the host irides, strongly fluorescent spider-like cells with short branching processes and a negative nucleus were seen. These cells were more numerous and more strongly fluorescent in grafted irides as compared to recipient irides and in the 6-day iris grafts as compared to the 2-day grafts. In all probability, the GFA-positive fibers and cells forming a network in adult irides from different species and in embryonic and grafted rat irides represent Schwann cells and their processes. The cellular origin of the spider-like cells in the iris grafts is less clear.

Animals↗

PubMed1984

Astrocytes in smears of CNS tissues as visualized by GFA and vimentin immunofluorescence.

A technique is described using immunocytochemistry in which smears of fresh unfixed brain tissue combined with antibodies against glial fibrillary acidic protein (GFA) or vimentin is used to visualize astrocytes. In rats the amount of GFA-positive cells was much lower in cortex cerebri smears than in smears of other cortical regions such as the olfactory bulb, hippocampus and cerebellum. A few vimentin positive astrocytes were also seen in hippocampus and cortex cerebri smears. Smears of spinal cord white matter contained astrocytes with very long processes as visualized by GFA immunohistochemistry while grey matter astrocytes had somewhat shorter processes. Using either anti-GFA or anti-vimentin procedures, smears of neonatal rat brain showed immature star-shaped cell-like structures. In contrast, neonatal spinal cord smears contained typical spidershaped astrocytes equally well visualized with both antisera. Both GFA- and vimentin-positive astrocytes were visualized in smears of normal human brain tissue, though the number of vimentin-positive cell bodies was very low. To our knowledge, this is the first description of vimentin-positive astrocytes in normal human brain. For studies of astrocyte development and morphology the technique has several advantages. It allows inspection of separated individual cells without sectioning, and, since no tissue culture is performed there is no risk that the amounts and/or distribution of either GFA or vimentin will be changed. Thus the technique facilitates comparative studies of GFA- and vimentin-positive astrocytes in different areas of the normal CNS as well as in different experimental and pathological conditions. We conclude that GFA and vimentin immunocytochemistry of CNS smears is a rapid and useful method of visualizing individual astrocytes in animals and man.

Animals↗

PubMed1984

Some toxic effects of lead, other metals and antibacterial agents on the nervous system--animal experiment models.

Modern man is chronically exposed to lead levels in the biosphere, several times higher than the natural level that once existed. There is much concern about the possible adverse effects of this population-wide low-level lead exposure, particularly on the developing organism, where the central nervous system may be a primary target for lead. We have developed animal test systems which permit temporal and spatial discrimination of possible effects of lead and other potentially neurotoxic agents in the environment on the developing central nervous system, as well as on different types of peripheral nerves in the adult individual. In one experimental design, defined areas of the fetal rat brain are grafted to the anterior chamber of the eye of adult rat recipients which are exposed to lead (1% PbAc in drinking water). Such grafts will become vascularized from the host iris and continue their development in oculo. Thus the grafted brain tissue and the host brain will share circulation and therefore be exposed to exactly the same amounts of lead simultaneously. Studies of cerebellar grafts revealed that although there was a normal gross cytological development in the presence of lead, there was a severe, permanent impairment of the spontaneous discharge rates of the grafted Purkinje neurons as observed with electrophysiological techniques long after cessation of the lead treatment. The host Purkinje neurons were not affected. A similar, although less dramatic, impairment of cerebellar function could then be demonstrated in intact animals when newborn rats were given lead (8 mg PbAc/kg i.p.) during the first 20 days of life and then studied as adults. In other areas of the fetal central nervous system grafted to the eye, lead caused disturbed growth (substantia nigra, cortex cerebri). A screening technique for potentially harmful effects on autonomic and sensory nerve terminals in adult rats makes use of intraocular injections of agents to be tested. Morphological and histochemical changes of the innervation apparatus of the iris are then studied in iris whole-mount preparations. Lead causes an adrenergic hyperinnervation of the iris. Computer-based image analysis revealed severe degenerative effects by hexachlorophene and chlorhexidine. These studies demonstrate the usefulness of the intraocular grafts and the intraocular injection technique and the need to apply both structural and functional techniques in order to detect possible neurotoxic actions of xenobiotics. The techniques have revealed hitherto unknown toxic actions of lead on cerebellar function.

Adrenergic Fibers↗

PubMed1983

Normalization of spiroperidol binding in the denervated rat striatum by homologous grafts of substantia nigra.

Transplantation of embryonic substantia nigra into the adult rat brain decreases the motor asymmetry that is produced by dopamine receptor supersensitivity after a unilateral lesion of the substantia nigra. The authors report that this effect of transplantation is specific to grafts of substantia nigra. They also report that, in conjunction with the decrease in motor asymmetry, these grafts cause postsynaptic dopaminergic binding sites to return to normal density as measured by tritiated spiroperidol autoradiography. Thus, in animals with brain lesions, grafts of substantia nigra produce a long-term alteration in the functional status of host brain cell receptors that is associated with a reduction in the behavioral deficit.

Animals↗