PubMed Health⌕ Search

Biomedical subjects

D F Emerich

Publications and source records attributed to D F Emerich.

At least 55 records · Page 3Linked to original sources
PubMed1997

Blind rats are not profoundly impaired in the reference memory Morris water maze and cannot be clearly discriminated from rats with cognitive deficits in the cued platform task.

The Morris water maze is commonly used to test cognitive function in rodent models of neurological disorders including age-related cognitive deficits. It is often assumed that the most profoundly impaired aged rats may be blind due to retinal degeneration, and it has been reported that animals with visual sensory deficits can be identified based on their performance in a cued platform task. The results of the present study demonstrate that blind rats can perform surprisingly well in the reference memory version of the Morris water maze, and that blind rats cannot be selectively excluded based on performance in the cued platform task since atropine-treated rats also perform poorly in the cued platform task. Future studies may be able to develop screening procedures that help to eliminate subjects with non-cognitive deficits, but the present results do not support the use of the cued platform or straight swim task as screening procedures. Experimenters must be careful to consider the role that visual sensory function and other non-cognitive factors may have in performance of the spatial learning Morris water maze, and also the role that severe cognitive deficits may have in performance of the cued platform task.

Animals↗
PubMed1996

Alleviation of behavioral deficits in aged rodents following implantation of encapsulated GDNF-producing fibroblasts.

The present study examined the effects of encapsulated cells which were genetically modified to secrete human glail-derived neurotrophic factor (hGDNF) on the motor deficits in aged rodents. Prior to implantation, animals were tested on a battery of motor tasks. Spontaneous locomotion and motor coordination was evaluated in young (5 month) and aged (20 months) rats. Aged animals tested for spontaneous locomotor activity were found to be hypoactive relative to young animals. Compared to the young animals the aged animals also: (1) were impaired on a bar pressing task, (2) were unable to descend a wooden pole covered with wire mesh in a coordinated manner, (3) fell more rapidly from a rotating rod and (4) were unable to maintain their balance on a series of wooden beams of varying widths. Following baseline testing, aged animals received either no implant, encapsulated baby hamster kidney fibroblast cells that were modified to produce hGDNF (BHK-hGDNF) or encapsulated BHK cells which were not modified to produce hGDNF (BHK-Control) implanted bilaterally into the striatum. Following surgery, a significant increase in locomotor activity and bar pressing was observed in those aged animals receiving BHK-hGDNF implants. Bar pressing in aged animals receiving BHK-Control cells was improved to a lesser extent and reached the level of performance seen in young rats. No recovery was observed in the animals receiving BHK-Control cell-loaded capsules on any of the other motor tasks. Histological analysis revealed that implants of hGDNF-producing cells produced a marked increase in the density of tyrosine hydroxylase staining in the striatum adjacent to the implant site. This increased staining was not seen in animals receiving BHK-Control cells. Histological analysis also revealed the presence of viable BHK-hGDNF cells within the capsules that continued to produce hGDNF as measured by ELISA. These results indicate that polymer-encapsulated hGDNF-secreting cells survive following implantation into aged rats and may be useful for treating some of the behavioral consequences of aging or disorders characterized by dopaminergic hypofunction.

Aging↗
PubMed1996

Implants of encapsulated human CNTF-producing fibroblasts prevent behavioral deficits and striatal degeneration in a rodent model of Huntington's disease.

Delivery of neurotrophic molecules to the CNS has gained considerable attention as a potential treatment strategy for neurological disorders. In the present study, a DHFR-based expression vector containing the human ciliary neurotrophic factor (hCNTF) was transfected into a baby hamster kidney fibroblast cell line (BHK). Using a polymeric device, encapsulated BHK-control cells and those secreting hCNTF (BHK-hCNTF) were transplanted unilaterally into the rat lateral ventricle. Twelve days later, the same animals received unilateral injections of quinolinic acid (QA; 225 nmol) into the ipsilateral striatum. After surgery, animals were behaviorally tested for apomorphine-induced rotation behavior and for skilled forelimb function using the staircase test. Rats receiving BHK-hCNTF cells rotated significantly less than animals receiving BHK-control cells. No behavioral effects of hCNTF were observed on the staircase test. Nissl-stained sections demonstrated that BHK-hCNTF cells significantly reduced the extent of striatal damage produced by QA. Quantitative analysis of striatal neurons further demonstrated that both choline acetyltransferase- and GAD-immunoreactive neurons were protected by BHK-hCNTF implants. In contrast, a similar loss of NADPH-diaphorase-positive cells was observed in the striatum of both implant groups. Analysis of retrieved capsules revealed numerous viable and mitotically active BHK cells that continued to secrete hCNTF. These results support the concepts that implants of polymer-encapsulated hCNTF-releasing cells can be used to protect striatal neurons from excitotoxic damage and that this strategy may ultimately prove relevant for the treatment of Huntington's disease.

Animals↗
PubMed1996

Chromaffin cell survival from both young and old donors is enhanced by co-grafts of polymer-encapsulated human NGF-secreting cells.

Following polymer-encapsulation, human nerve growth factor-secreting baby hamster kidney fibroblasts (BHK-hNGF) were implanted into the striatum of hemiparkinsonian rats together with unencapsulated adrenal medullary chromaffin cells from either young (2 weeks) or old (12 months) donor rats. Animals receiving both BHK-hNGF cells and chromaffin cells exhibited significant decreases (39-56%) in apomorphine-induced rotational behaviour which was equivalent regardless of the age of the donor tissue. Histological analysis revealed that while survival of chromaffin cells without hNGF support was poor, co-grafts of adrenal medulla and BHK/hNGF cells increased chromaffin cell survival by 20 times. Again, this effect was independent of the age of the donor tissue. Retrieved capsules contained numerous viable encapsulated BHK-hNGF cells which continued to release hNGF. These results further indicate the potential use of intrastriatal implantation of encapsulated hNGF-secreting cells for augmenting the survival of co-grafted chromaffin cells as well as promoting the functional recovery of hemiparkinsonian rats.

Age Factors↗
PubMed1996

Polymer-encapsulated genetically modified cells continue to secrete human nerve growth factor for over one year in rat ventricles: behavioral and anatomical consequences.

The long-term delivery of growth factors and other proteins into the CNS at putatively therapeutic yet safe levels continues to be technically constrained. In the present studies, the gene encoding human nerve growth factor (hNGF), introduced into a dihydrofolate reductase-based pNUT expression vector system, was engineered into a clonal baby hamster kidney (BHK) cell line. BHK-hNGF23 and mock-transfected cells were encapsulated in an immunoisolating polymeric device and transplanted into the lateral ventricles of healthy young adult rats for 13.5 months. As measured by ELISA, nanogram quantities of hNGF were released by encapsulated cells both prior to implantation (3.6 +/- 0.8 ng/device/24 h) and upon removal from rat lateral ventricles after 13.5 months in vivo (2.2 +/- 0.4 ng/ device/24 h). In addition, the hNGF released into the tissue culture medium was biologically active. Long-term encapsulated cell survival was confirmed by histologic analysis. The presence of genomic DNAs (hNGF transgene), as determined by PCR analyses, revealed that the transgene copy number from the recovered BHK-hNGF23 cells after 13.5 months in vivo was equivalent to preimplant levels. No deleterious effects from hNGF were detectable on body weight, mortality rate, motor/ambulatory function, or cognitive function as assessed with the Morris water maze and delayed matching to position in healthy young adult rats. In addition, there was no evidence that hNGF from these encapsulated cells produced hyperalgesia. Only tests of somatosensory thresholds revealed statistically significant effects related to the hNGF delivered in the present study, and that effect was limited to a decrease in the number of trials to asymptote. Animals receiving BHK-hNGF23 implants exhibited a marked hypertrophy of cholinergic neurons within the striatum (22% increase) and nucleus basalis (7% increase) but not the medial septum ipsilateral to the capsule. Moreover a robust sprouting of cholinergic fibers was observed within the frontal cortex and lateral septum proximal to the implant. These results indicate that encapsulated xenogeneic cells provide a safe and effective method for the long-term delivery of hNGF and potentially other neurotrophic factors within the CNS.

Animals↗
PubMed1996

Individual differences in the hotplate test and effects of habituation on sensitivity to morphine.

Hotplate studies rarely match subjects into groups and often use high temperatures that are less sensitive to the effects of mild analgesics. Subjects may not be matched into groups because it has not been clearly demonstrated that there are reliable and robust individual differences in performance on the hotplate, and out of concern that the testing required to match subjects into groups might reduce the sensitivity of the task to mild analgesics by producing 'behavioral tolerance'. Higher hotplate temperatures may be preferred because they reduce variability in response latencies, and it may be assumed that this precludes the need to match subjects into groups. The results of the present study demonstrate that there are reliable and robust differences among individuals tested on the hotplate, regardless of whether the hotplate is 50 degrees C or 55 degrees C (alpha's > 0.90). The present results also confirm that lower hotplate temperatures are much more sensitive to the effects of mild analgesics: increased response latencies following a low dose of morphine (3 mg/kg) could be reliably detected with only 8 rats at 50 degrees C, while the same dose would not be detected reliably at 55 degrees C unless more than 55 rats were tested. Finally, there was no evidence that habituation to the hotplate produced 'behavioral tolerance' or reduced the sensitivity of the test to the effects of morphine. These findings suggest that hotplate studies should match subjects into groups and use lower hotplate temperatures in order to increase the sensitivity of the test, but also out of an ethical obligation to minimize the intensity of the noxious stimulus and the number of animals exposed to it.

Analgesics, Opioid↗
PubMed1996

Intrastriatal implants of polymer encapsulated cells genetically modified to secrete human nerve growth factor: trophic effects upon cholinergic and noncholinergic striatal neurons.

Nerve growth factor selectively prevents the degeneration of cholinergic neurons following intrastriatal infusion but rescues both cholinergic and noncholinergic striatal neurons if the nerve growth factor is secreted from grafts of genetically modified fibroblasts. The present study evaluated whether grafted fibroblasts genetically modified to secrete human nerve growth factor could provide trophic influences upon intact cholinergic and noncholinergic striatal neurons. Unilateral striatal grafts of polymer-encapsulated cells genetically modified to secrete human nerve growth factor induced hypertrophy and significantly increased the optical density of choline acetyltransferase-immunoreactive striatal neurons one, two, and four weeks post-transplantation relative to rats receiving identical grafts missing only the human nerve growth factor construct. Nerve growth factor secreting grafts also induced a hypertrophy of noncholinergic neuropeptide Y-immunoreactive striatal neurons one, two, and four weeks post-transplantation. Glutamic acid decarboxylase-immunoreactive neurons were unaffected by the human nerve growth factors secreting grafts. The effects upon choline acetyltransferase-immunoreactive and neuropeptide Y-immunoreactive striatal neurons dissipated following retrieval of the implants. Immunocytochemistry for nerve growth factor revealed intense graft-derived immunoreactivity for up to 1000 microns from the capsule extending along the dorsoventral axis of the striatum. Nerve growth factor-immunoreactivity was also observed within a subpopulation of striatal neurons and may represent nerve growth factor consumer neurons which retrogradely transported graft-derived nerve growth factor. When explanted, grafts produced 2-4 ng human nerve growth factor/24 h over the time course of this study indicating that this level of continuous human nerve growth factor secretion was sufficient to mediate the effects presently observed.

Animals↗
PubMed1996

Validation of a rodent model of Parkinson's Disease: evidence of a therapeutic window for oral Sinemet.

Behavioral measures of parkinsonism that are more clinically relevant than rotometry have been developed for rats with severe unilateral dopamine depletions, and the validity of these measures is supported by reports that these parkinsonian symptoms are attenuated by drugs that are effective in the clinical setting. Although the therapeutic gold standard, L-DOPA:carbidopa (Sinemet), effectively attenuates parkinsonian symptoms, the beneficial effects of this drug are limited by the dyskinesias that it produces at higher doses. The range of effective doses, from the minimum dose that produces beneficial effects to the dose that produces intolerable dyskinesias, is referred to as the "therapeutic window." It would be extremely valuable to assess, preclinically, the effects of novel treatments on the therapeutic window for Sinemet. The results of the present study support the validity of nondrug-induced measures of parkinsonian symptoms in dopamine-depleted rats. Neurological measures revealed large behavioral deficits in the affected forelimb analogous to the deficits exhibited in Parkinson's disease patients, and these deficits were significantly attenuated with some doses of oral Sinemet (30-40 mg/kg). These drug effects on measures of parkinsonism were specific to performance with the affected limb. At slightly higher doses (50 mg/ kg), the rats were untestable due to severe dyskinesias. The results of the present study suggest that it is possible to investigate the therapeutic potential of novel treatments as well as their effects on the therapeutic window of oral Sinemet in this rodent model of Parkinson's disease.

Administration, Oral↗
PubMed1996

Cografting with polymer-encapsulated human nerve growth factor-secreting cells and chromaffin cell survival and behavioral recovery in hemiparkinsonian rats.

Encapsulated cell grafting is one approach for the delivery of neurotransmitters and/or neurotrophic factors to the brain. Baby hamster kidney (BHK) cells were genetically modified to secrete high levels of human nerve growth factor (hNGF). Following polymer encapsulation, these cells were implanted into the left lateral ventricle or the left striatum 1.5 mm away from striatally cografted unencapsulated adrenal medullary chromaffin cells in hemiparkinsonian rats. Although the animals receiving adrenal medulla alone or adrenal medulla with intraventricular hNGF-secreting cell grafting did not show recovery of apomorphine-induced rotational behavior, the animals receiving adrenal medulla with intrastriatal hNGF-secreting cell implants showed a significant recovery of rotational behavior 2 and 4 weeks after transplantation. Histological analysis revealed that in animals receiving adrenal medulla with intraventricular hNGF-secreting cell grafting, the number of tyrosine hydroxylase-immunoreactive (TH-IR) surviving chromaffin cells tended to be higher (approximately five to six times) than in animals receiving adrenal medulla alone; however, this increase did not reach statistical significance. In contrast, in animals receiving adrenal medullary cells together with intrastriatal hNGF-secreting cells, the number of TH-IR surviving chromaffin cells was more than 20 times higher than that in animals receiving adrenal medullary cells alone. Analysis of retrieved capsules revealed that hNGF continued to be released by encapsulated BHK-hNGF cells after 4 weeks in vivo. Moreover, histological analysis confirmed the presence of numerous viable encapsulated BHK-hNGF cells. These results indicate the potential use of intrastriatal implantation of encapsulated hNGF-secreting cells for augmenting the survival of cografted chromaffin cells as well as promoting the functional recovery of hemiparkinsonian rats. These data indicate that this approach may have potential application for treating Parkinson's disease.

Animals↗
PubMed1994

The aged monkey basal forebrain: rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor.

Six Rhesus monkeys between 24 and 29 years of age received unilateral transections of the fornix. Three monkeys then received intraventricular transplants of polymer-encapsulated baby hamster kidney (BHK) fibroblasts that had been genetically modified to secrete human nerve growth factor (hNGF). The remaining three monkeys received identical grafts except the cells were not modified to secrete hNGF. Monkeys receiving the fornix transection and control grafts displayed extensive reductions in the number of choline acetyltransferase- (57-75%) and p75 NGF receptor- (53%) immunoreactive medial septal neurons ipsilateral to the lesion/implant. In contrast, monkeys receiving transplants of encapsulated hNGF-secreting cells display only a modest loss of choline acetyltransferase- (0-36%) and p75 NGF receptor-(7-22.4%) immunoreactive septal neurons. Additionally, all monkeys receiving the hNGF-secreting implants, but none receiving control implants, displayed robust sprouting of cholinergic fibers within the septum ipsilateral to the transplant. Just prior to sacrifice, the capsules were retrieved and found to contain viable BHK cells releasing biologically relevant levels of hNGF. These data demonstrate that hNGF can provide trophic and tropic influences to aged primate basal forebrain neurons undergoing lesion-induced degeneration, supporting the contention that hNGF may prevent the degeneration of basal forebrain neurons in Alzheimer disease.

Aging↗
PubMed1994

Implants of polymer-encapsulated human NGF-secreting cells in the nonhuman primate: rescue and sprouting of degenerating cholinergic basal forebrain neurons.

Baby hamster kidney (BHK) cells were genetically modified to secrete high levels of human nerve growth factor (BHK-hNGF). Following polymer encapsulation, these cells were implanted into the lateral ventricle of four cynomolgus monkeys immediately following a unilateral transection/aspiration of the fornix. Three control monkeys received identical implants, with the exception that the BHK cells were not genetically modified to secrete hNGF and thus differed only by the hNGF construct. One monkey received a fornix transection only. All monkeys displayed complete transections of the fornix as revealed by a comprehensive loss of acetylcholinesterase-containing fibers within the hippocampus ipsilateral to the lesion. Control monkeys that were either unimplanted or received BHK-control (non-NGF secreting) cell implants did not differ from each other and displayed extensive losses of choline acetyltransferase and p75 NGF receptor (NGFr)-immunoreactive neurons within the medial septum (MS; 53 and 54%, respectively) and vertical limb of the diagonal band (VLDB; 21 and 30%, respectively) ipsilateral to the lesion. In contrast, monkeys receiving implants of BHK-hNGF cells exhibited a only a modest loss of cholinergic neurons within the septum (19 and 20%, respectively) and VLDB (7%). Furthermore, only implants of hNGF-secreting cells induced a dense sprouting of cholinergic fibers within the septum, which ramified against the ependymal lining of the ventricle adjacent to the transplant site. Examination of the capsules retreived from monkeys just prior to their death revealed an abundance of cells that produced detectable levels of hNGF in a sufficient concentration to differentiate PC12A cells in culture. These findings support the use of polymer-encapsulated cell therapy as a potential treatment for neurodegenerative diseases such as Alzheimer disease where basal forebrain degeneration is a consistent pathological feature. Moreover, this encapsulated xenogeneic system may provide therapeutically effective levels of a number of neurotrophic factors, alone or in combination, to select populations of neurons within the central nervous system.

Acetylcholine↗
PubMed1994

Polymer-encapsulated cells genetically modified to secrete human nerve growth factor promote the survival of axotomized septal cholinergic neurons.

Effective treatments for neurodegenerative disorders are limited by our inability to alter the progression of the diseases. A number of proteins have specific neuroprotective activities in vitro; however, the delivery of these factors into the central nervous system over the long term at therapeutic levels has been difficult to achieve. BHK cells engineered to express and release human nerve growth factor were encapsulated in an immunoisolation polymeric device and transplanted into both fimbria-fornix-lesioned rat brains and naive controls. In the lesioned rat brain, chronic delivery of human nerve growth factor by the encapsulated BHK cells provided nearly complete protection of axotomized medial septal cholinergic neurons. Human nerve growth factor continued to be released by encapsulated cells upon removal from the aspirative site after 3 weeks or from normal rat striatum after 3 and 6 months in vivo. Long-term encapsulated cell survival was confirmed by histologic analysis. This encapsulated xenogeneic system may provide therapeutically effective amounts of a number of neurotrophic factors, alone or in combination, to virtually any site within the body.

Analysis of Variance↗
PubMed1994

Implantation of polymer-encapsulated human nerve growth factor-secreting fibroblasts attenuates the behavioral and neuropathological consequences of quinolinic acid injections into rodent striatum.

Delivery of neurotrophic molecules to the central nervous system has gained considerable attention as a potential strategy for the treatment of neurological disorders. In the present study, a DHFR-based expression vector containing the human nerve growth factor gene (hNGF) was transfected into a baby hamster fibroblast cell line (BHK). Using an immunoisolatory polymeric device, encapsulated BHK-control cells and those secreting hNGF (BHK-hNGF) were transplanted unilaterally into rat lateral ventricles. Three days later, the same animals received unilateral injections of quinolinic acid (QA, 225 nmol) or the saline vehicle into the ipsilateral striatum. Approximately 2 weeks following surgery, animals were tested for apomorphine-induced rotation behavior. Animals which received BHK-hNGF cells rotated significantly less than those animals receiving BHK-control cells or QA alone. Histological analysis 29-30 days following capsule implantation demonstrated that BHK-hNGF cells attenuated the extent of host neural damage produced by QA as assessed by a sparing of ChAT- and NADPH-d-positive neurons. Moreover, a lessened GFAP reaction was apparent within the striatum of animals receiving BHK-hNGF cells. As measured by ELISA, hNGF was released by the encapsulated BHK-hNGF cells prior to implantation and following removal. Morphology of retrieved capsules revealed numerous viable and mitotically active BHK cells. These results suggest that implantation of polymer-encapsulated hNGF-releasing cells can be used to protect neurons from excitotoxin damage.

Animals↗
PubMed1994

Intrastriatal implants of polymer-encapsulated PC12 cells: effects on motor function in aged rats.

1. The feasibility of ameliorating the motor deficits in aged rats was evaluated in animals receiving polymer-encapsulated PC12 cells. 2. Motor coordination and balance was evaluated in young (5-6 month) and aged (24-25 month) rats. Compared to the young animals, the aged animals fell more rapidly from a rotating rod and were unable to maintain their balance on a series of wooden beams of varying widths. 3. Following baseline testing, aged animals received either no implant, empty capsules or PC12 cell-loaded capsules implanted bilaterally into the striatum. 4. Three weeks following surgery, animals were re-tested and a significant improvement in balance on the rotorod and wooden beams was observed in those aged animals receiving PC12 cell-loaded capsules. No improvements or decrements in performance were observed in those animals receiving empty. Histological analysis revealed the presence of surviving tyrosine hydroxylase-positive PC12 cells randomly distributed within the capsules.

Animals↗
PubMed1994

Cell transplantation for central nervous system disorders.

Initially, the specific aim of transplantation studies was to investigate the regenerative capabilities of the mammalian nervous system. From this underlying impetus, a myriad of knowledge, spanning from molecular biology to neurobiology, has enhanced our understanding of regeneration and the applicability of fetal tissue transplantation in treating various neurodegenerative diseases. Current evidence suggests that transplantation of fetal neural tissue ameliorates the neurobiological and behavioral changes observed in animal models of central nervous system (CNS) disorders. In light of numerous basic science studies, clinical trials have begun to evaluate the potential of neural transplantation in treating human diseases. Indeed, modest progress has been reported in the treatment of Parkinson's disease. However, whereas fetal tissue transplantation has reached considerable success, it has also been observed to produce either no beneficial effects, magnify existing behavioral abnormalities, or even produce a unique constellation of deficits. Thus, while the prospects are promising, further investigations aimed at improving and refining existing transplantation paradigms are warranted before neural transplantation techniques can be of widespread value. This review article attempts to provide an overview of the neuroanatomical, neurochemical, and behavioral effects produced by transplanted fetal tissue in several animal models of CNS disorders. We have attempted to present both positive and adverse effects and to critically analyze the suitability of neural transplantation as a therapy for the various neurological disorders. In addition, alternative approaches, including the use of encapsulated neural tissue implants and genetically engineered cell lines along with their clinical potential, are discussed when appropriate.

Animals↗
PubMed1993

Substance P containing polymer implants protect against striatal excitotoxicity.

The present study examined whether substance P (Sub P) could protect against quinolinic acid (QA)-induced lesions of the striatum, as measured by a loss of striatal D1 dopamine receptors. Sub P was extruded into Evac polymer rods for slow release. One 4 mm rod segment was implanted unilaterally into the striatum of each rat. One week later, animals received a striatal injection of QA (50, 75 or 100 nmol/microliters) medial to the implanted rod. Controls received QA alone. Three weeks later, there was a dose-dependent loss of D1 receptors following QA. Sub P rods protected the striatum from QA-induced D1 receptor loss at this time. These results support the neuroprotection role of Sub P on excitotoxicity.

Animals↗
PubMed1993

Polymer-encapsulated PC12 cells promote recovery of motor function in aged rats.

The feasibility of using polymer-encapsulated PC12 cells to ameliorate the motor deficits in aged rats was evaluated. Spontaneous locomotion and motor coordination was evaluated in young (5-6 month) and aged (24-25 month) rats. Aged animals tested for spontaneous locomotor activity in Digiscan animal activity monitors were found to be hypoactive relative to young animals. Compared to the young animals the aged animals: (1) remained suspended from a horizontal wire for less time, (2) were unable to descend a wooden pole covered with wire mesh in a coordinated manner, (3) fell more rapidly from a rotating rod, and (4) were unable to maintain their balance on a series of wooden beams with either a square or rounded top of varying widths. Prior to implantation PC12 cell-loaded capsules were chromatographically characterized for catecholamine release. Following baseline testing, aged animals received either no implant, empty capsules, or PC12 cell-loaded capsules implanted bilaterally into the striatum. Three weeks following surgery, animals were retested and a significant improvement in balance on the rotorod and wooden beams was observed in those aged animals receiving PC12 cell-loaded capsules. No recovery was observed in the animals receiving PC12 cell-loaded capsules on any of the other motor tasks. Likewise, no improvement was observed on any behavioral measure in those animals receiving empty capsules. Histological analysis revealed the presence of numerous surviving tyrosine hydroxylase-positive PC12 cells within the capsules. Encapsulated PC12 cells survive following implantation into aged rats and such a technique may be useful for treating some of the behavioral consequences of aging.

Aging↗