Biomedical subjects

D F Emerich

Publications and source records attributed to D F Emerich.

At least 91 records · Page 5Linked to original sources

PubMed1990

Neural basis of behavior: animal models of human conditions.

A variety of neurological disorders including Alzheimer's, Parkinson's, and Huntington's diseases are characterized by abnormalities within specific neuroanatomical and/or neurochemical systems. Approaches to the treatment of these and other neurological disorders are limited. The development and refinement of animal models which closely mimic human disease states would help elucidate the underlying neurobiological mechanisms of the disease as well as suggest novel therapeutic strategies for their prevention or alleviation. This symposium presents a variety of animal models that have helped us in understanding the human condition. The present introduction presents some clinically relevant findings obtained from basic experimental studies with animal models of Huntington's disease (HD) and Tourette Syndrome (TS). These studies demonstrate that animal models can provide a greater understanding of the symptomatology of disease states as well as suggest innovative new treatments.

Animals↗

PubMed1989

GM1 ganglioside attenuates the behavioral deficits but not the granule cell damage produced by intradentate colchicine.

Bilateral injection of 3.5 micrograms of colchicine into the dentate gyrus produced hyperactivity, impaired retention of a passive avoidance task, and enhanced the motor stimulant effects of a dopaminergic agonist (apomorphine) and the analgesic effects of morphine. In contrast, there was no alteration in scopolamine-induced hyperactivity. These effects were associated with a decrease in the thickness of the granule cell layer in both the superior and inferior blade of the dentate gyrus and a coincident decrease in the size of the overlying dentate molecular layer. Intraperitoneal injection of monosialoganglioside GM1 (30 mg/kg) beginning 3 days prior to surgery and continuing for 25 days following surgery appeared to limit the extent and duration of these behavioral effects. GM1 facilitated recovery of motor activity and attenuated the impaired retention of the passive avoidance task and the alterations in pharmacological sensitivity following intradentate injection of colchicine. Despite the facilitative effects of GM1 on behavior histological analysis of the hippocampus did not reveal a protective effect of this compound on colchicine-induced granule cell destruction. The results of these studies suggest that intradentate injection of colchicine is a useful model of human diseases where only restricted populations of neurons are damaged. Furthermore, these studies indicate that the use of monosialoganglioside GM1 might be a useful primary or adjunct approach to the treatment of neurodegenerative disorders and their behavioral sequelae.

Animals↗

PubMed1989

Destruction of specific hippocampal cell fields increases ornithine decarboxylase activity: modulation of the biochemical but not the histological changes by ganglioside GM1.

Unilateral injection of colchicine into the dentate gyrus, kainic acid into the CA3 pyramidal cell field, or cerebrospinal fluid into either site produced significant increases in ornithine decarboxylase (ODC) activity in both the injected and noninjected hippocampi. The magnitude as well as the time course of these changes varied with the cytotoxin, the site of injection, and whether or not animals had been pretreated with ganglioside GM1. The ganglioside regimen reduced the ODC response in the injected hippocampus but increased it on the side contralateral to the colchicine injection. In contrast, GM1 enhanced the ODC response produced by kainic acid in the injected but not the uninjected hippocampus. In a subsequent study morphometric analysis of the hippocampus revealed that pretreatment with GM1 did not alter the extent of hippocampal injury induced by either cytotoxin. These data indicate that the changes in ODC activity observed following hippocampal damage represent a complex set of biochemical changes that might serve to protect primary or secondary sites of insult and/or to promote either adaptive or maladaptive neural reorganization. Ganglioside GM1 altered the ODC response without minimizing the histopathological changes induced by the cytotoxins. The role of polyamines in neural, behavioral, and synaptic plasticity is currently under study.

Animals↗

PubMed1989

Selective working memory impairments following intradentate injection of colchicine: attenuation of the behavioral but not the neuropathological effects by gangliosides GM1 and AGF2.

Bilateral injection of 3.5 micrograms of colchicine into the dentate gyrus produced specific learning and memory impairments together with a selective pattern of neuropathology. Animals injected with colchicine exhibited a significant impairment in their ability to perform the working memory, but not the reference memory, component of a multiple component T-maze task. These deficits were transient and over time all animals were able to reaquire the task to preoperative levels of performance. Histological analyses revealed that intradentate injection of colchicine produced 1) a significant decrease in the width of both the superior and inferior blades of the dentate gyrus reflecting the extensive loss of granule cells, 2) a related decrease in the size of the dentate molecular layer, and 3) a decrease in the number of cholinergic neurons in the medial septum. The second phase of the experiment demonstrated that gangliosides GM1 and AGF2 did not prevent the initial impairments in working memory performance induced by colchicine but rather accelerated the rate at which it recovered. The gangliosides did not decrease the extent of neuronal damage; there was no sparing of granule cells in the dentate gyrus or cholinergic neurons in the medial septum. These data further support a role for the hippocampus in working memory processes and they also indicate that gangliosides GM1 and AGF2 might be useful for treating the behavioral deficits induced by hippocampal damage.

Animals↗

PubMed1989

Effects of intrahippocampal administration of colchicine on incentive contrast and on radial maze performance.

The behavior of rats given intradentate injections of the neurotoxin colchicine was examined in three experimental settings. In Experiment 1, colchicine-treated, artificial cerebrospinal fluid (CSF)-treated, and untreated animals did not differ in the intake of 32% and 4% sucrose solutions, nor did they differ in degree of successive negative contrast when the 32% solution was changed to 4% sucrose. In Experiment 2, the colchicine-treated and CSF-treated animals did not differ in degree of suppression in the intake of a 0.15% saccharin solution when it preceded 32% sucrose in once-daily pairings (anticipatory contrast), nor did they differ in reversal performance when saccharin-sucrose and saccharin-saccharin pairings were reversed. In Experiment 3, the colchicine-treated animals were substantially impaired in radial-arm maze performance compared with CSF-treated controls. These results suggest that a completely functioning hippocampus is not necessary for the memory of reward quality, the comparison of rewards, the suppression of behavior when reward is decreased, the formation of associations between two levels of reward, and the reversal of this association, as long as these processes are reflected in consummatory behavior. The data are interpreted in terms of differences between instrumental behavior and sensory memory and/or consummatory behavior--an interpretation that is not incompatible with a deficiency in working memory in the animals with lesions.

Animals↗

PubMed1988

The hippocampus as a common target of neurotoxic agents.

The hippocampus (HPC) is in a strategic position to process information derived from the polymodal association areas of the neocortex and to redistribute it to cortical and subcortical regions involved in the modulation of complex behavioral processes. Several converging lines of evidence indicate that the HPC and its cholinergic input are an important neurobiological substrate for learning and memory processes. Destruction of the HPC proper, its afferent projections, and its cholinergic innervation, produces a persistent impairment in cognitive function. Since alterations in learning and memory are a common consequence of toxicant exposure it is possible that the HPC is an important target site for neurotoxicity. In fact, the HPC has been shown to be preferentially susceptible to a wide variety of toxic insults and disease states. For example, the HPC is damaged by a number of environmental toxicants (heavy metals and their alkyl derivatives), metabolic perturbations, neuroactive viruses, cerebrovascular insufficiency, and neurodegenerative diseases. The susceptibility of this structure to a broad spectrum of insults and its involvement in higher order cognitive processes makes it an important focal point for studies of behavioral and neurological toxicity. Neurobiological characteristics of the HPC that might make this structure uniquely susceptible to toxic insult are discussed.

Brain Diseases↗

PubMed1985

Effects of 6-hydroxydopamine-induced catecholamine depletion on shock-precipitated wall climbing of infant rat pups.

Sprague-Dawley rat pups were intracisternally injected with 6-hydroxydopamine (6OHDA) or vehicle on postnatal Day 3 and tested for footshock-precipitated wall climbing behavior every 48 hr from postnatal Days 5 through 17. The 6OHDA treatment was observed to lower brain catecholamine levels, particularly in forebrain, and to decrease the incidence of wall climbing. This attenuation in the amount of wall climbing did not appear to be related to any neurotoxin-induced alterations in general motor activity, body weight, or body temperature. It also did not appear that the depression in wall climbing seen in 6OHDA-treated animals was related to an observed neurotoxin-induced increase in shock sensitivity, given that amount of wall climbing was observed to be positively correlated with footshock intensity. These results provide further support that catecholaminergic systems are involved in the elicitation of wall climbing behavior. The 6OHDA treatment did not alter the ontogenetic time course of disappearance of this behavior pattern, suggesting that maturational changes occurring in forebrain catecholaminergic terminals may not be critical for the dissipation of wall climbing following the second postnatal week.

Animals↗

PubMedDate not supplied

Apolipoprotein E-immunoreactivity in aged rhesus monkey cortex: colocalization with amyloid plaques.

In the present study, we examined the relationship between ApoE and amyloid containing profiles within the cerebral cortex of young, middle aged, and aged Rhesus monkeys. Polymerase chain reaction analysis revealed a pattern consistent with the ApoE e4 phenotype in the rhesus monkey similar to that reported in humans. We found numerous ApoE immunoreactive plaques within the temporal neocortex and amygdala, whereas the hippocampus contained only a few such plaques. Although virtually all ApoE-immunoreactive plaques coexpressed beta-amyloid, most plaques were beta A4 positive/ApoE immunonegative within the aged monkey cortex. Moreover, we observed a close correspondence between ApoE and thioflavin-positive (i.e., amyloid) plaques suggesting that ApoE may play a critical role in the conversion of beta A4 to its beta-pleated form. Because ApoE, beta A4 and amyloid are expressed in plaques within the aged Rhesus macaque cortex, this species may provide an in vivo model for investigations aimed at clarifying the interactions between these proteins in normal and pathologic aging.

Aging↗

PubMedDate not supplied

Xenotransplantation of neonatal porcine liver cells.

Xenotransplantation of porcine liver cell types may provide a means of overcoming the shortage of suitable donor tissues to treat hepatic diseases characterized by inherited inborn errors of metabolism or protein production. Here we report the successful isolation, culture, and xenotransplantation of liver cells harvested from 7- to 10-day-old piglets. Liver cells were isolated and cultured immediately after harvesting. Cell viability was excellent (>90%) over the duration of the in vitro studies (3 weeks) and the cultured cells continued to significantly proliferate. These cells also retained their normal secretory and metabolic capabilities as determined by continued release of albumin, factor 8, and indocyanin green (ICG) uptake. After 3 weeks in culture, porcine liver cells were loaded into immunoisolatory macro devices (Theracyte devices) and placed into the intraperitoneal cavity of immunocompetant CD1 mice. Eight weeks later, the devices were retrieved and the cells analyzed for posttransplant determinations of survival and function. Post mortem analysis confirmed that the cell-loaded devices were biocompatible, and were well-tolerated without inducing any notable inflammatory reaction in the tissues immediately surrounding the encapsulated cells. Finally, the encapsulated liver cells remained viable and functional as determined by histologic analyses and ICG uptake/release. The successful harvesting, culturing, and xenotransplantation of functional neonatal pig liver cells support the continued development of this approach for treating a range of currently undertreated or intractable hepatic diseases.

Animals↗

PubMedDate not supplied

Behavioral effects of gangliosides: anatomical considerations.

Gangliosides are endogenous sialic acid containing glycospingolipids which are highly concentrated in the central nervous system. Although they were first characterized over 40 years ago, the function(s) played by this unique class of lipids remain largely unknown. Gangliosides have been suggested to play a prominent role in both normal and abnormal developmental processes. In addition, several lines of convergent evidence have indicated that gangliosides exert pronounced trophic effects following damage to peripheral and central nerves. Gangliosides have been shown to (1) enhance cell survival and outgrowth in cultured and developing neurons; (2) promote the regeneration of damaged peripheral and central nerves, and (3) facilitate behavioral recovery by altering the pattern, extent and persistence of the biochemical, morphological and behavioral changes induced by neural trauma. Little is known, however, concerning the neurobiological mechanisms which subserve the behavioral protection afforded by ganglioside treatment. This review focuses on the evidence suggesting that gangliosides mediate functional recovery by minimizing primary or secondary cell loss or promoting the regeneration or sprouting of damaged central nerves subsequent to injury. An understanding of the mechanisms by which gangliosides produce their effects may lead to the development of more efficacious and rational primary or adjunct pharmacological treatments for central nervous system disorders.

Animals↗

PubMedDate not supplied

Effect of fetal striatal and astrocyte transplants into unilateral excitotoxin-lesioned striatum.

Studies have suggested that neurotrophic mechanisms may underlie transplant-induced functional recovery. Astrocytes have been reported to be a source of neurotrophic factors. The present study examined the possible role of cultured astrocytes in promoting recovery of apomorphine-induced rotation behavior in rats with unilateral kainic acid (KA) lesions of the striatum. Five weeks after the lesions, one group of rats received fetal striatal tissue (E17) transplants, another group received transplants of cultured astrocyte suspension, and the remaining rats received sham transplants and served as controls. Apomorphine-induced rotation behavior was tested 4 weeks after the KA lesions, and 5 and 10 weeks following the transplantation. The KA-induced rotation behavior was reduced by the striatal transplants but not by the cultured astrocyte transplants 5 and 10 weeks following the transplantation. Histochemical analysis indicated that the striatal transplants had survived and grown and contained neurons and glia with similar morphology to those in the host brain. Immunocytochemical analysis of the astrocyte transplant sites revealed heavy glial fibrillary acidic protein and OX-42 staining in the transplant areas, suggesting that the transplanted astrocytes may have survived in the host brain. Although fetal striatal transplants can ameliorate apomorphine-induced rotation behavior, transplants of astrocytes alone may not be sufficient to reverse the functional deficits produced by KA lesions.

Animals↗

PubMedDate not supplied

Polymer-encapsulated Schwannoma cells expressing human nerve growth factor promote the survival of cholinergic neurons after a fimbria-fornix transection.

Many investigators have recently used genetically modified primary fibroblasts of fibroblast cell lines (e.g., 3T3, 208F, or BHK cells) to deliver recombinant nerve growth factor (NGF) into the CNS. In the current study, SCT-1 cells, a Schwannoma cell line derived from a transgenic mouse, were transfected with a human NGF (hNGF) cDNA. After selection, these cells were encased within a polymer capsule and implanted into the ventricles of fimbria-fornix lesioned rats. Encapsulated, non-transfected cells served as controls. Results demonstrated that the hNGF transgene is expressed for at least 3 weeks after implantation. Moreover, the cells did not overgrow the capsule. Recombinant hNGF was able to save > 70% of lesioned cholinergic neurons, as assessed by NGF-receptor (NGFr) and choline acetyltransferase (ChAT) immunohistochemistry, from cell death. The number of cholinergic neurons in animals that received control capsules (i.e., nontransfected SCT-1 cells) was similar to lesion only animals (i.e., approximately 27% and approximately 33% for NGFr- and ChAT-positive neurons, respectively. These results show that SCT-1 cells can be used to deliver biologically active hNGF into the lesioned rat brain.

Animals↗

PubMedDate not supplied

Encapsulated PC12 cell transplants into hemiparkinsonian monkeys: a behavioral, neuroanatomical, and neurochemical analysis.

Four cynomolgus monkeys were trained on a hand reaching task and then rendered hemiparkinsonian with an intracarotid injection of n-methyl 4 phenyl 1,2,3,6, tetrahydropyridine (MPTP). Performance on this task with the limb contralateral to the MPTP injection was significantly impaired following the lesion. Three monkeys received implants of polymer-encapsulated containing PC12 cells into the caudate nucleus and putamen. One monkey received identical implants of empty capsules and served as a control. After a transient improvement, limb use in the control monkey dissipated and returned to post-MPTP disability. Two of the three PC12 cell grafted monkeys recovered performance on the hand reach task to near normal levels for up to 6.5 mo posttransplantation. Capsules retrieved from the monkeys who recovered limb function postimplantation contained numerous viable PC12 cells that continued to release levodopa, basal dopamine, and potassium evoked dopamine. In contrast, capsules retrieved from the PC12 cell-grafted monkey which did not recover limb use on the hand reach task contained few cells which secreted negligible or undetectable levels of levodopa and dopamine. Interestingly, functional disability was not reinstated following removal of the capsules. Neuroanatomical and neurochemical evaluation of the grafted striatum did not reveal a host-derived sprouting response of catecholaminergic or indolaminergic fibers. These data indicate that xenografts of PC12 cells can survive for up to 6.5 mo in nonimmunosuppressed monkeys when immunoisolated via polymer encapsulation. Moreover, these cells continue to secrete high levels of levodopa and dopamine and induce recovery of motor function in parkinsonian nonhuman primates.

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

PubMedDate not supplied

Effects of intraventricular encapsulated hNGF-secreting fibroblasts in aged rats.

Exogenous NGF administered into the central nervous system (CNS) has been reported to improve cognitive function in aged rats. However, concerns have been expressed about the risks involved with supplying NGF to the CNS. In this study, baby hamster kidney cells (BHK) genetically modified to secrete human NGF (hNGF) were encapsulated in semipermeable membranes and implanted intraventricularly. ChAT/LNGFR-positive basal forebrain neurons were shown to atrophy and degenerate with age, especially in cognitively impaired rats. The encapsulated BHK-NGF cells produced less than 10% of doses previously reported to be effective, but this was sufficient to increase the size of ChAT/LNGFR-positive basal forebrain neurons in the aged and learning-impaired rats to the size of the neurons in young healthy rats. The hNGF from these encapsulated cells also improved performance in a repeated-acquisition version of the Morris water maze spatial learning task in learning-impaired 20.6- and 26.7-mo-old rats. Furthermore, there was no evidence that these doses of hNGF impaired Morris water maze performance in the youngest 3.3-5.4 mo rats, and analyses of mortality rates, body weights, somatosensory thresholds, potential hyperalgesia, and activity levels, suggested that these levels of exogenous hNGF are not toxic or harmful to aged rats. These results suggest that CNS-implanted semipermeable membranes, containing genetically modified xenogeneic cells continuously producing these levels of hNGF, attenuate age-related cognitive deficits in nonimmunosuppressed aged rats, and that both the surgical implantation procedure and long-term exposure to low doses of hNGF appear safe in aged rats.

Aging↗

PubMedDate not supplied

Continued presence of intrastriatal but not intraventricular polymer-encapsulated PC12 cells is required for alleviation of behavioral deficits in Parkinsonian rodents.

To date, few studies have systematically evaluated the most appropriate location for grafting catecholaminergic cells as a potential treatment for Parkinson's disease (PD). The following study was conducted to determine 1) if placement of catecholamine-secreting encapsulated PC12 cells into the lateral ventricle of 6-OHDA-treated rats is as effective as intrastriatal implants on reducing apomorphine-induced rotational behavior, and 2) to determine if the survival of encapsulated PC12 cells is differentially affected by the implant site. Polymerencapsulated PC12 cells were implanted into either the striatum or lateral ventricle of unilateral 6-OHDA-lesioned rats. Animals were tested for apomorphine-induced rotations over a 6-wk period. Only those animals that received intrastriatal implants of encapsulated PC12 cells showed a reduction in rotation behavior. Moreover, removal of the devices from the striatum resulted in a return to preimplant rotation levels. Postexplant neurochemical analyses demonstrated that the potassium-evoked L-dopa device output increased in vivo while the potassium-evoked dopamine output from the devices decreased over time in vivo. The location of the implant significantly affected catecholamine output from the PC12 cell-loaded devices. The increase in potassium-evoked L-dopa output was greatest, as was the decrease in potassium-evoked dopamine output, from those devices implanted in the striatum. Basal output of dopamine and DOPAC was also significantly higher from devices explanted from the lateral ventricle. These results demonstrate that the continued presence of intrastriatal implants of encapsulated PC12 cells is required to maintain the behavioral effects in 6-OHDA-lesioned rats. In addition, the site of implantation appears to affect device output. These results provide additional support for intraparenchymal delivery of L-dopa and dopamine via polymer encapsulation as a possible treatment for PD.

Animals↗

PubMedDate not supplied

Cellular delivery of human CNTF prevents motor and cognitive dysfunction in a rodent model of Huntington's disease.

The delivery of ciliary neurotrophic factor (CNTF) to the central nervous system has recently been proposed as a potential means of halting or slowing the neural degeneration associated with Huntington's disease (HD). The following set of experiments examined, in detail, the ability of human CNTF (hCNTF) to prevent the onset of behavioral dysfunction in a rodent model of HD. A DHFR-based expression vector containing the hCNTF gene was transfected into a baby hamster kidney fibroblast cell line (BHK). Using a polymeric device, encapsulated BHK-control cells and those secreting hCNTF were transplanted bilaterally into rat lateral ventricles. Eight days later, the same animals received bilateral injections of quinolinic acid (QA, 225 nmol) into the previously implanted striata. A third group received sham surgery (incision only) and served as a normal control group. Bilateral infusions of QA produced a significant loss of body weight and mortality that was prevented by prior implantation with hCNTF-secreting cells. Moreover, QA produced a marked hyperactivity, an inability to use the forelimbs to retrieve food pellets in a staircase test, increased the latency of the rats to remove adhesive stimuli from their paws, and decreased the number of steps taken in a bracing test that assessed motor rigidity. Finally, the QA-infused animals were impaired in tests of cognitive function-the Morris water maze spatial learning task, and the delayed nonmatching-to-position operant test of working memory. Prior implantation with hCNTF-secreting cells prevented the onset of all the above deficits such that implanted animals were nondistinguishable from sham-lesioned controls. At the conclusion of behavioral testing, 19 days following QA, the animals were sacrificed for neurochemical determination of striatal choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) levels. This analysis revealed that QA decreased striatal ChAT levels by 35% and striatal GAD levels by 45%. In contrast, hCNTF-treated animals did not exhibit any decrease in ChAT levels and only a 10% decrease in GAD levels. These results support the concepts that implants of polymer-encapsulated hCNTF-releasing cells can be used to protect striatal neurons from excitotoxic damage, produce extensive behavioral protection as a result of that neuronal sparing, and that this strategy may ultimately prove relevant for the treatment of HD.

Animals↗

PubMedDate not supplied

Polymer-encapsulated PC-12 cells demonstrate high-affinity uptake of dopamine in vitro and 18F-Dopa uptake and metabolism after intracerebral implantation in nonhuman primates.

Intracranial implantation of polymer-encapsulated PC-12 cells has been shown to improve motor behavioral performance in animal models of Parkinson's disease. The purpose of this blinded study was to examine whether such improvement is associated with the active uptake and metabolism of dopamine precursors by intracerebrally implanted polymer-encapsulated PC-12 cells. In an in vitro experiment we demonstrate that 3H-dopamine uptake by PC-12 cells was 10(8) fmol/min x 10(6) cells, and that this uptake can be specifically blocked 88% by the addition of 10nM of nomifensine. In the in vivo experiments, polymer-encapsulated PC-12 cells were implanted in four MPTP-treated monkeys into the left deep parietal white matter (R1) or left striatum (R2-4). A fifth MPTP-treated monkey (R5) served as a control and received left striatal implants of empty capsules. 18-F-Dopa Positron Emission Tomography (PET) imaging was performed on each monkey before and after implantation surgery by blinded investigators. PET images obtained 5-13 wk after implantation demonstrated well delineated focal areas of high 18F-dopa uptake in R1, R2, and R4. The focal area of high 18F-dopa uptake in R1 precisely coregistered on a brain magnetic resonance image to the site of implantation. R3 (in whom the polymer-encapsulated PC-12 cells demonstrated poor cell survival upon explantation) and R5 (empty capsules) failed to demonstrate any area of increased 18F-dopa uptake in their PET images. Histological examination of the host brain revealed no sprouting of dopaminergic nerve terminals around the implantation sites of the polymer-encapsulated PC-12 cells. These results indicate that the previously noted behavioral improvement after intrastriatal implantation of polymer encapsulated PC-12 cells is at least in part due to their highly specific uptake and metabolism of dopamine precursors. Furthermore, these data suggest that polymer-encapsulated PC-12 cells can store, reuptake, and functionally replenish dopamine and therefore, may be an effective treatment for Parkinson's disease.

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

PubMedDate not supplied

Therapeutic potential of a polymer-encapsulated L-DOPA and dopamine-producing cell line in rodent and primate models of Parkinson's disease.

Encapsulation of cells within polymer membranes prior to transplantation provides a novel means of achieving continuous, site-specific delivery of therapeutic molecules to the CNS. The use of encapsulated dopamine-secreting cells that can be transplanted directly into the striatum has particular appeal for the treatment of Parkinson's disease. This article provides a brief and timely review of the progress that has been made over the past decade using encapsulated PC12 cells as a means of delivering dopamine and L-DOPA to the striatum in rodent and primate models of Parkinson's disease. The polymer membranes are well tolerated and biocompatible. Encapsulated PC12 cells survive in vivo for up to 6 mo, they release dopamine into the surrounding host striatum, and they clearly improve behavioral function in both dopamine-depleted rodents and primates. Although these results are promising, fundamental issues remain concerning the extent of dopamine diffusion from the polymer membranes and the number of devices needed for behavioral improvement, and the duration and consistency of cell viability and device output. Nevertheless, this technology appears to be a promising means of avoiding many of the practical, societal, and ethical issues that have been associated with other transplantation approaches.

Animals↗