Biomedical subjects

J R Sladek

Publications and source records attributed to J R Sladek.

At least 19 recordsLinked to original sources

PubMed1991

Ultrastructural changes in magnocellular neurons from the supraoptic nucleus of aged rats.

Magnocellular neurosecretory neurons in the supraoptic nucleus were examined in aged and young subjects to assess the ultrastructural correlates of cellular activity including cell, nuclear and nucleolar size, as well as the percentage of the cell occupied by Golgi, mitochondrial and rough endoplasmic reticulum compartments. Morphometric analysis was performed on arbitrarily selected cell profiles using a computerized morphometry protocol. Approximately 50% of those neurons examined from aged subjects exhibited a statistically significant increase relative to the young rats in total cell area and all cellular organelles examined except nuclear area. Moreover, an increase in the number and density (per unit membrane area) of synaptic contacts onto those neurons was observed. These findings suggest an increase in synthetic activity by a subpopulation of supraoptic magnocellular neurons, and support the concept of neuronal plasticity in aged rats.

Aging↗

PubMed1991

Grafting of fetal substantia nigra to striatum reverses behavioral deficits induced by MPTP in primates: a comparison with other types of grafts as controls.

Fetal substantia nigra (SN) cells were transplanted into the caudate nucleus (CN) of four vervet monkeys (Cercopithecus aethiops sabaeus) that had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP treatment appears to produce a syndrome similar to that observed in patients with idiopathic Parkinson's disease. Normal and parkinsonian behaviors were quantitated by trained observers 5 days/week. Twenty-eight behaviors based on previous factor analyses were individually scored and rated. Parkinsonian signs included freezing, head and limb tremor, difficulty in eating, delayed initiation of movement, poverty of movement, tremor that stopped with intention, decreased response to threats, and lying immobile in the cage. These signs were combined to give an overall rating of parkinsonism. A summary measure of 'normal' healthy behavior was also examined, including such behaviors as yawning, scratching, self-grooming, shifting, and eating. Overall ratings of parkinsonism increased and those of healthy behavior decreased after MPTP. In the 4 monkeys grafted with fetal SN cells into the CN, behavior returned to pre-treatment levels by the time of sacrifice (2, 5, or 7.5 months after grafting). Three control subjects were transplanted with either SN cells into an inappropriate brain site (cortex) or inappropriate, non-dopaminergic, cells (cerebellar) into the CN. Subjects were also compared with three control animals that did not receive MPTP but received cryopreserved or fresh SN and other cells into the CN. Only MPTP-treated subjects that received SN cells into the CN showed evidence of a reversal of the MPTP syndrome after transplantation. In addition, grafting in animals that were not MPTP-treated did not appear to affect behavior. This paper reports the specific behavioral effects of severe MPTP toxicity that were or were not reversed after transplantation and suggests that only fetal SN cells grafted into the CN may be able to reverse behavioral deficits in MPTP-treated monkeys.

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

PubMed1991

Chronic levodopa impairs the recovery of dopamine agonist-induced rotational behavior following neural grafting.

The effect of chronic levodopa treatment on the function of embryonic mesencephalic tissue grafts was assessed in rats by monitoring rotational behavior elicited by dopamine (DA) agonists before and after neural grafting. Rats were given unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway and baseline measures of rotational behavior induced by D1 receptor stimulation, D2 receptor stimulation, or amphetamine were determined. Subsequently, DA grafts were implanted into the lesioned striatum and chronic regimens of either saline or levodopa began one day after neural grafting and were continued for 7 weeks. Rotational behavior elicited by the D1 agonist, SKF 38393, was completely attenuated throughout the six-week-period following the commencement of levodopa treatment, regardless of the absence or presence of a DA graft. Conversely, rotational behavior elicited by the D2 agonist, quinpirole, was significantly elevated in ungrafted animals receiving chronic levodopa. Grafted animals receiving chronic levodopa did not show a significant reduction in rotational behavior, whereas grafted animals receiving chronic saline showed a significant 67% reduction in quinpirole-induced rotational behavior. Amphetamine-induced rotational behavior was reduced in both levodopa and saline treated grafted animals, however grafted animals receiving chronic levodopa treatment showed a reduction of rotational behavior that was uncharacteristic and less compensatory than that observed in grafted animals receiving chronic saline treatment. Morphology of grafts indicate that there were areas of impaired neurite outgrowth of TH-positive fibers in animals treated with levodopa. The results of the present study suggest that the impaired recovery in quinpirole- and amphetamine-induced rotational behavior in grafted animals receiving chronic levodopa treatment may be related to (1) impaired graft function, (2) an alteration in pre- and postsynaptic mechanisms in the host DAergic system, or (3) a combined effect of (1) and (2).

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1991

Striatal implants protect the host striatum against quinolinic acid toxicity.

Quinolinic acid (QA) and related excitotoxins produce a pattern of neuronal loss and neurochemical changes in the rat striatum similar to that of patients suffering from Huntington's disease, suggesting neurotoxicity is important in the etiology of that disease. Thus, strategies for limiting excitotoxin-induced striatal damage, like that caused by QA, may be of great benefit to these individuals. Accordingly, we tested the ability of both neural and non-neural tissue implants to protect the rat striatum against a subsequent QA challenge. Our results demonstrated that recipients of fetal striatal grafts were significantly less affected by striatal injections of QA than non-grafted animals. In contrast to the latter, fetal striatal tissue recipients did not exhibit apomorphine-induced rotation behavior and showed a sparing of cholinergic and enkephalinergic systems normally lost following QA injections. Animals grafted with adult rat sciatic nerve, adrenal medulla or adipose tissue all showed a less dramatic behavioral protection and sparing of cholinergic and enkephalinergic systems. These results suggest that fetal striatal tissue exerts an optimal, and perhaps specific protective influence on the host brain.

Adrenal Medulla↗

PubMed1990

MPTP reduces dopamine and norepinephrine concentrations in the supplementary motor area and cingulate cortex of the primate.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to primates produces many of the biochemical, morphological and behavioral changes that occur in Parkinson's disease. MPTP-induced degeneration of the mesostriatal dopamine innervation has been well documented. In the present study, concentrations of dopamine and norepinephrine in cortical regions surrounding the cingulate sulcus were assessed, and were found to be markedly decreased in symptomatic MPTP-treated vervet monkeys; these results parallel the cortical involvement in Parkinson's disease. Dopamine and norepinephrine levels were not reduced in a group of asymptomatic MPTP-treated monkeys that suffered large losses of striatal dopamine concentration. If therefore appears that the dopaminergic innervations of the supplementary motor area and cingulate cortex are susceptible to MPTP-induced degeneration, but are less vulnerable than the striatal dopamine innervation.

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

PubMed1990

MPTP-induced parkinsonism: relative changes in dopamine concentration in subregions of substantia nigra, ventral tegmental area and retrorubral field of symptomatic and asymptomatic vervet monkeys.

Dopamine (DA) and homovanillic acid (HVA) concentrations were measured in subregions of substantia nigra, ventral tegmental area and retrorubral field in vervet monkeys 1 to 2 months after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Identical MPTP treatment regimens produced animals with different degrees of parkinsonism. In asymptomatic monkeys, changes in DA and HVA concentrations in the midbrain DA regions were relatively small and involved central substantia nigra and dorsomedial ventral tegmental area. In contrast, changes in symptomatic monkeys were more severe and widespread, significantly affecting all examined subregions of substantia nigra (greater than 75% DA depletion), both dorsomedial and ventromedial ventral tegmental area and lateral, but not medial, retrorubral field. The data indicate that DA neurons in subregions of substantia nigra, ventral tegmental area and retrorubral field are not equally susceptible to MPTP toxicity. The pattern of MPTP-induced DA and HVA losses in the vervet monkey mesostriatal dopaminergic system may resemble postencephalitic Parkinson's disease more closely than idiopathic Parkinson's disease.

Animals↗

PubMed1990

Chronic levodopa impairs morphological development of grafted embryonic dopamine neurons.

Degeneration and plasticity of dopamine (DA) neurons may be influenced by their own neurotransmitter and/or metabolic by-products. Substances with known neurotoxic properties, such as hydrogen peroxide and 6-hydroxydopamine, are produced during oxidation of DA. Additionally, DA can directly regulate neurite outgrowth in both invertebrate and vertebrate species. We have begun to investigate the influence of increased local transmitter concentrations on the morphological plasticity of neurons by examining the effect of chronic levodopa, a drug that increases DA synthesis, on grafted embryonic nigral DA neurons in a rat model of experimental parkinsonism and in monolayer cell cultures. Results from our in vivo investigation show that although chronic levodopa does not significantly affect the number of surviving grafted cells, morphological development of these embryonic DA neurons appears impaired. Levodopa administered chronically to fetal DA neurons in culture results in a decreased number of surviving neurons as well as a reduction in neurite outgrowth with increasing concentration of levodopa ranging from 10(-8) to 10(-4) M. This information provides further evidence to support the hypothesis that excess DA or its metabolites can influence the survival and growth of DA neurons. These results may be important in the design of pharmacotherapy for Parkinson's disease and the combination of drug and neural grafting therapies in this disorder.

Animals↗

PubMed1990

Embryonic mesencephalic and striatal co-grafts: development of grafted dopamine neurons and functional recovery.

Previous neural grafting studies have shown that embryonic dopamine neurons survive transplantation into the parenchyma of the brain; however, fiber outgrowth from those cells is often limited to the immediate vicinity of the graft. More extensive outgrowth is desirable for promoting and maintaining functional recovery of damaged neural systems in animal models as well as human neurodegenerative disorders. The present study examined the possibility of stimulating fiber outgrowth of grafted neurons by simultaneously grafting dopamine neurons with their embryonic target cells. Subsequent functional recovery was evaluated in concert with morphological characteristics of these grafts. Co-grafts of embryonic mesencephalic and striatal cells were implanted into the DA-denervated striatum of rats previously given unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Two types of co-grafts were implanted into the DA-denervated striatum: mixed or separate cell suspensions. Tyrosine hydroxylase immunocytochemical analysis of brain sections containing co-grafts revealed extensive arborization of TH-positive neurons in both types of co-grafts. When mesencephalic and striatal nerve cells were implanted into separate sites, TH-positive neurons extended projections that appeared to preferentially reach regions occupied by embryonic striatal neurons. Moreover, the average size of TH-positive cell bodies found in mixed or separate co-grafts was significantly larger than the size of those found in single mesencephalic grafts. Amphetamine-induced rotational behavior was used to assess the degree of functional recovery. In the majority of co-grafted animals, rotational behavior was attenuated by 3 weeks and reversed (amphetamine-induced contralateral rotation) by 5 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

PubMed1990

Improvements in MPTP-induced object retrieval deficits and behavioral deficits after fetal nigral grafting in monkeys.

Improvements in MPTP-induced deficits were only found in subjects that received fetal substantia nigra transplants into the caudate nucleus. The MPTP-induced deficits were assessed using an object retrieval task that examined cognitive and subtle motor performance and by behavioral observation to determine the overall status of the subjects. Subjects that were also moderately or severely impaired by MPTP administration but that received inappropriate donor cells or implant sites (cerebellum to CN or SN to cortex) did not show any evidence of behavioral recovery. These subjects could not respond on the task in the months after grafting and were sacrificed, showing no improvements in parkinsonian signs or healthy behavior signs, up to 5-6 months after surgery. Grafting of SN cells into the striatum of non-MPTP lesioned subjects failed to modify normal behavior or induce abnormal behavior determined by our 2 behavioral assessment methods. In those monkeys that received the appropriate transplants, TH immunohistochemistry revealed that cells of the fetal substantia nigra grafted into the caudate nucleus survived and extended neurites into the host striatum. Indeed, grafted dopamine neurons were often associated with appreciable innervation of the caudate nucleus and appeared to be well incorporated into the host brain. In contrast, examination of the striatum of subjects in the inappropriate-graft group (e.g., cerebellar cells grafted into the caudate) showed no evidence of TH staining within the graft or host caudate nucleus. This indicated that there was no evidence of dopamine neurons present in the grafted tissue and that the mere presence of a fetal graft did not appear to induce sprouting in these MPTP-treated subjects. Although behavioral recovery occurred in only those monkeys that received appropriate transplants (fetal SN to host CN) and not in those that received inappropriate grafts (fetal cerebellum to CN or fetal SN to cortex), the CSF HVA levels did not distinguish those monkeys with improved parkinsonism from those that remained severely parkinsonian. The finding that in some SN-CN grafted subjects reported here, there was evidence of increased dopamine and lowered HVA/dopamine ratio in the vicinity of the SN grafts (cf. Elsworth et al., 1990b) is consistent with the hypothesis that graft-derived or graft-induced dopamine production is responsible for behavioral recovery. In addition, the finding that CSF HVA levels in non-MPTP lesioned subjects were unchanged by fetal SN grafts further indicates that CSF HVA levels may not be sufficiently sensitive to changes in central dopamine production to reflect release of dopamine from relatively small grafts that may, in lesioned subjects, modify behavior.(ABSTRACT TRUNCATED AT 400 WORDS)

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

PubMed1990

Cognitive and motor deficits in the performance of an object retrieval task with a barrier-detour in monkeys (Cercopithecus aethiops sabaeus) treated with MPTP: long-term performance and effect of transparency of the barrier.

To assess the stability of neural deficits produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the performance of monkeys on an object retrieval (detour) task was studied. The task required retrieval of a banana slice from a transparent box open on one side and fastened to a tray in front of the cage. The orientation of the open side, position on the tray, and position of the banana in the box were manipulated to vary the difficulty of the trials. Six African green monkeys (Cercopithecus aethiops sabaeus) were treated with MPTP (1.5-1.6 mg/kg cumulative doses over 4-5 days) and compared with 5 saline-treated control monkeys. The MPTP-treated monkeys had no gross neurological deficits but did have motor and cognitive deficits during acquisition of the object retrieval task 8-12 months after treatment (J. R. Taylor, Elsworth, Roth, Sladek, & Redmond, in press). Performance on the task was examined for 3 months after it had been learned. The MPTP-treated subjects reached at the barrier (transparent side) significantly more than controls and were less successful at retrieving the reward on the 1st reach than controls. Although they took longer to initiate the reach and had more motor problems than controls, they were as likely as controls to retrieve the reward in the end. These deficits remained stable throughout testing. An opaque but otherwise identical box was used randomly on some trials. MPTP-treated subjects decreased barrier reaches to control levels on trials in which the opaque box was used, whereas motor problems increased compared with trials in which the transparent box was used. The task can detect subtle performance deficits similar to those found in Parkinson's disease.

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

PubMed1990

Cognitive and motor deficits in the acquisition of an object retrieval/detour task in MPTP-treated monkeys.

To assess functional changes following treatment with 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) in monkeys, we studied a task that reveals sensitivity to dopamine deficits under various conditions. The task required retrieval of a banana slice from a transparent box that is open on one side and fastened to a tray. Successful performance required the subject to suppress a tendency to reach directly at the reward while (1) orientation of the open side, (2) position on the tray, and (3) position of the banana in the box were manipulated in order to vary the cognitive and motor difficulty of the trial. African green monkeys (Cercopithecus aethiops sabaeus) were treated with MPTP (1.5-1.6 mg/kg cumulative dose over 4-5 days). A control group was sham treated (n = 12). MPTP-treated subjects either became severely symptomatic, showing motor impairments that prevented them from performing, or showed no gross motor impairment (n = 6) in spite of major depletions in dopamine concentrations. MPTP-treated subjects showed impaired acquisition of the task when tested 8-12 months later. They made more errors during the sessions, specifically on the trials that were related to cognitive complexity, such as attempting to reach directly towards the reward through the transparent side of the box (a barrier reach), instead of reaching around it (detour) into the open side, as well as other awkward, perseverative or delayed reaches. MPTP appears to cause both cognitive and motor deficits in the acquisition of this task 8-12 months after treatment, even in the group of monkeys which never showed gross motor deficits.

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

PubMed1990

Fluorescence histochemical techniques for catecholamines as tools in neurobiology.

Formaldehyde-induced and glyoxylic-acid-induced fluorescence histochemistry permits the tissue localization of catecholamines in the central nervous system (CNS) and peripheral nervous system (PNS), and in culture. Counterstains such as ethidium bromide provide excellent background identification of specific innervated regions in both the CNS and the periphery. Use of fluorescence histochemistry with immunocytochemistry can elucidate catecholamine-peptide relationships. Gelatin-ink perfusion used with fluorescence histochemistry permits the investigation of neuro-vascular relationships and documentation of vascular and parenchymal compartmentation of innervation. Combined use of fluorescence histochemistry and retrograde tracing methods demonstrates the specific cellular sources of innervation of target regions. Micropunch neurochemical analysis provides quantitative data for correlation with fluorescence histochemistry within a target region of innervation, and microspectrofluorometric analysis provides a semi-quantitative evaluation of the amount of fluorophore within a target region or within specific subcellular compartments such as the cell body or terminals.

Animals↗

PubMed1990

Dopamine cell replacement: Parkinson's disease.

Significant progress in neural transplantation has been observed over the last several decades. As a neuroanatomical tool, neural transplantation studies are able to examine the mechanisms involved in the development and integration of neurons into the complex neural circuitries of the brain. Today, embryonic neural tissue can be successfully transplanted as solid tissue chunks or as dissociated cell suspensions. Within the parenchyma of the brain, transplanted embryonic neurons develop mature morphology and do not appear to invoke an immunological response by the lost immune system. Not only do these neurons exhibit robust development but there is also evidence that transplanted neurons restore some degree of function to neurologically damaged circuitry; however, the extent of reintegration into the host neural circuitry still remains unclear. Moreover, the long-term survival and functioning of transplanted nerve cells also remains an unanswered question. Advances in the emerging field of genetic engineering may eventually lead to genetically modified neurons that are capable of synthesizing neurotrophic factors or missing neurotransmitters and restoring function in brain-damaged areas. The use of neural transplantation to replace damaged nerve cells in neurodegenerative disorders, such as Alzheimer's or Parkinson's disease, is promising based on our current knowledge. However, our basic scientific knowledge of neural transplants is incomplete and warrants a prudent approach toward application of neural transplantation techniques in clinical research.

Adrenal Medulla↗

PubMed1990

Physiological and biochemical indices of neurohypophyseal function in the aging Fischer rat.

In order to resolve conflicting reports in the literature on the effect of aging on the hypothalamo neurohypophyseal system (HNS) in rats, multiple parameters associated with the HNS were evaluated in young (4 months), fully mature (14 months), and old (25 months) Fischer 344 rats under basal and stimulated conditions. The hypothalamic hormones oxytocin and vasopressin were compared in radioimmunoassay of serum, urine, brain and pituitary. Information on body weight, water intake, urine output, serum hematocrit and plasma osmolality was also obtained from the same subjects and analyzed together with these data. Finally, semi quantitative histofluorescence assessment of the noradrenergic innervation of the mediobasal hypothalamus from the same animals was performed to determine the extent of central afferent input to the HNS with advancing age. The circulating levels of vasopressin and oxytocin did not significantly differ in the three age groups under basal conditions. Serum vasopressin concentration was increased following water deprivation, and the increase was comparable in all age groups. Serum oxytocin was also increased following water deprivation in all groups, but the increase was greater in the 25-month-old rats relative to the 4-month-old rats. Urinary excretion of vasopressin was used as an index of daily vasopressin secretion. The urinary concentration of vasopressin was less in aged rats relative to young controls, though an increased urine volume in the mature and old animals meant that total vasopressin excretion in the urine was comparable at all ages studied. The increased urine volume in the mature and aged rats does not appear to reflect a decrease in renal sensitivity to vasopressin, since all age groups demonstrated a comparable reduction in urine volume during water deprivation, at comparable concentrations of circulating vasopressin. These data suggest that the increase in urine volume observed in the 14- and 25-month-old rats may be a function of increased fluid intake rather than hyperactivity in the HNS. The concentrations of both peptides were reduced in the posterior pituitary of aged rats, though again, the total amount of peptide in the gland did not change. Only oxytocin showed an age-related change in the hypothalamus, decreasing in the oldest subjects. These data indicate that the ability to secrete adequate quantities of vasopressin in response to dehydration is not compromised in Fisher 344 rats up to 25 months of age.

Aging↗

PubMed1989

Fetal research.

This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.

Cell Line↗

PubMed1989

Morphological, neurochemical, and behavioral characterizations associated with the combined treatment of diethyldithiocarbamate and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice.

Changes in striatal dopamine (DA) neurochemistry, tyrosine hydroxylase immunocytochemistry of DA fibers, and behavior following the combined administration of diethyldithiocarbamate (DDC) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice were assessed. The combined treatment of DDC and MPTP produced a dose-dependent decrease in striatal DA levels and a dose-related increase in the striatal DOPAC:DA ratio. Cumulative doses of MPTP equal to or exceeding 53.0 (26.5 mg/kg x 2. i.p.), given in combination with DDC, were effective in reducing striatal DA levels to less than 25% of control levels 2 weeks after treatment. Tyrosine hydroxylase immunocytochemistry revealed large deafferentation of DA terminal regions in striatum, moderate reductions in nucleus accumbens and dendritic regions of substantia nigra, and slight reductions in the number of DA cell bodies in substantia nigra. Mice treated with DDC and MPTP became hyperactive during the light phase of their diurnal cycle: psychopharmacological data suggest that postsynaptic DA receptors were supersensitized following this treatment. These data provide evidence that the combined treatment of DDC and MPTP produces severe and enduring depletion of mesostriatal DA, and also concomitant behavioral changes in mice.

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

PubMed1989

Fetal hypothalamic transplants promote survival and functional regeneration of axotomized adult supraoptic magnocellular neurons.

This study investigated the mechanisms by which fetal hypothalamic transplants promote functional recovery in neurohypophysectomized rats. Seven days after neurohypophysectomy (resulting in urine osmolalities of about 800 mOsm), young adult male Long-Evans rats received either fetal hypothalamic grafts (n = 10) or sham transplants (n = 7). Recovery from the lesioned-induced diabetes insipidus was monitored for 6 months and then the transplant sites were evaluated by immunocytochemistry. Surviving host supraoptic magnocellular neurons and neurophysin-positive grafted neurons were counted and their formation of neurohemal contacts evaluated by retrograde transport of systemically injected horseradish peroxidase (HRP). There were significantly more surviving supraoptic magnocellular neurons in neurohypophysectomized animals with median eminence-placed grafts (2236 +/- 261 neurons/animal) than in animals with ectopic tissue grafts (895 +/- 142 neurons/animal) or sham implants (1052 +/- 92 neurons/animal). Almost all surviving host magnocellular neurons were labeled with retrogradely transported HRP while virtually none of the grafted neurophysin positive cells showed evidence of HRP uptake. The degree of functional recovery was directly correlated with the increased survival of host neurons. By 8 weeks post-transplantation, animals with median eminence-placed grafts had recovered from their diabetes insipidus and could concentrate their urine to within normal limits (2,120 +/- 110 mOsm). This recovery was stable for the remainder of the 6 month test period. In contrast, animals with ectopic grafts and sham transplants had permanent deficits in fluid regulation. Our results provide evidence for the long-term capacity of fetal neural tissue implants to rescue host neurons from the cell death that typically occurs in the mature central nervous system after axotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Postmortem analysis of adrenal-medulla-to-caudate autograft in a patient with Parkinson's disease.

A 53-year-old physician who had a 10-year history of progressive idiopathic parkinsonism survived for 4 months after an autologous adrenal-medulla-to-right-caudate autograft but he received little clinical benefit. A small number of chromaffin cells in the graft site survived; they expressed neurofilament proteins and chromogranin A, but scant tyrosine hydroxylase. The striatum on both sides showed almost complete loss of [3H]mazindol binding to dopamine-uptake sites; the density of dopamine receptors was decreased adjacent to the transplant but increased rostral to the transplant. These results demonstrate that autografted chromaffin cells can survive for 4 months after transplantation and that related changes in dopamine receptors can be quantified.

Adrenal Medulla↗