Chapter 65 Preliminary report on adrenal medullary grafting and cografting with sural nerve in the treatment of hemiparkinson monkeys

Watts, Ray L.; Bakay, Roy A.E.; Herring, Carl J.; Sweeney, Kevin; Colbassani, Harold J.; Mandir, Allen S.; Byrd, Larry D.; Iuvone, P. Michael

doi:10.1016/s0079-6123(08)62648-5

Cited by 29 publications

(10 citation statements)

References 11 publications

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“…Increased TH‐positive fiber staining potentially reflecting stimulation of the host DA system previously has been reported in conjunction with implantation of adrenal chromaffin cells in rodents (Bohn et al, 1987; Bing et al, 1988; Date et al, 1990; Freed et al, 1990), monkeys (Bankiewicz et al, 1988; Fiandaca et al, 1988; Hansen et al, 1988; Plunkett et al, 1990; Watts et al, 1990) and humans (Kordower et al, 1991). For primates, increased fiber staining was associated with striatal tissue immediately surrounding the adrenal implant, or site of control implant damage, and extending along medial and ventral striatal regions following the trajectory of the entering mesostriatal system (Fiandaca et al, 1988).…”

Section: Discussionmentioning

confidence: 89%

Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP‐treated monkeys: Feasibility relevant to multiple‐target grafting as a therapy for Parkinson's disease

Collier

Sortwell

Elsworth

et al. 2001

J of Comparative Neurology

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Transplantation of embryonic dopamine (DA) neurons is being studied as an experimental replacement therapy for the DA-deficiency characteristic of Parkinson's disease. Some studies suggest that one of the limitations of this approach is that intrastriatal placement of implants fails to consistently restore completely normal movement. One potential cause of this suboptimal therapeutic outcome is that changes in the neural activity of several structures in the basal ganglia circuitry resulting from striatal DA depletion is not adequately normalized by graft-derived DA replacement in striatum alone. In the present study, we assessed the feasibility of grafting embryonic DA neurons into the substantia nigra (SN) of adult parkinsonian monkeys as an approach to restoration of the DA modulation of striatal-nigral afferents that is lost after degeneration of SN neurons. Sixteen St. Kitts African green monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) received implants of embryonic monkey ventral mesencephalon (VM), or sham implants, aimed at the rostral SN. At 6 months after grafting, staining for tyrosine hydroxylase (TH) indicated that grafted DA neurons survived at this site, albeit often in reduced numbers compared with VM grafts to striatum. Grafted neurons extended neurites into the parenchyma of the SN, but there was no evidence of lengthy extension of graft-derived neurites rostrally along the trajectory of the mesostriatal fiber system. A region-specific, modest increase in DA levels and TH-positive fiber density in the ventral-medial putamen was detected, accompanied by modest but significant decreases in parkinsonian behaviors at 5-6 months after grafting. Our findings support the view that grafting embryonic tissue to the SN is a feasible procedure in nonhuman primates that provides a modest but detectable benefit of its own. These results encourage the further development of multiple-target grafting strategies as a means of restoring modulation of anatomically widespread basal ganglia structures relevant to treatment of Parkinson's disease.

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Section: Discussionmentioning

confidence: 89%

Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP‐treated monkeys: Feasibility relevant to multiple‐target grafting as a therapy for Parkinson's disease

Collier

Sortwell

Elsworth

et al. 2001

J of Comparative Neurology

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“…Additional tests to measure arm and hand use are a leverpull task (Freed et al, 1988), reaction and movement time measures by release or move manipulanda in response to visual signals (Schneider et al, 1988), or combination of levers and touch screens (Ellis et al, 1992) and handle movements by wrist flexion and extension (Watts et al, 1990). These studies are usually performed on chaired monkeys, requiring long-term training, and limiting the resources to study many animals at the same time.…”

Section: Fine Motor Skills Tasksmentioning

confidence: 99%

Evaluation of animal models of Parkinson's disease for neuroprotective strategies

Emborg

2004

Journal of Neuroscience Methods

142

123

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“…We elected to use autologous adrenal medullary tissue co-grafted with peripheral nerve to enhance chromaffin cell sur vival as demonstrated in rodents (9,13), monkeys (22,31), and humans (10,32). Accordingly (11,31). An electromechanical dispenser delivered 300-mg food pellets to the monkey after appropriate responses.…”

Section: Introductionmentioning

confidence: 99%

Behavioral Evaluation of Hemiparkinsonian MPTP Monkeys following Dopamine Pharmacological Manipulation and Adrenal Co-Graft Transplantation

et al. 2000

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Bradykinesia and rigidity are the symptoms that most directly correlate with loss of striatal dopamine in Parkinson's disease. In the hemiparkinsonian (HP) monkey, this is represented by paucity of movement as measured by coli puterized movement analysis, diminished manual dexterity on clinical examination, and diminished performance on operant behavioral tasks. The present study used an MPTP-induced HP model in rhesus monkeys to evaluate the effectiveness of adrenal medullary and peripheral nerve co-grafts in diminishing parkinsonian symptoms. Unoperated controls (N = 4), surgical controls with caudate lesioning (N = 4), and caudate co-grafted (N = 4) HP monkeys demonstrated diminished movement in the home cage following MPTP. This behavior persisted in unoperated controls, but improved in both surgical control and co-grafted monkeys. Functional hand dexterity evaluations demonstrated similar impairment in all three groups but only surgical controls and co-grafted monkeys demonstrated improvement. In general, rotational behavior in response to apomorphine was consistent with recovery of function in surgical controls and co grafted monkeys, but marked between-subject variability precluded group statistical analyses. None of the monkeys could perform the operant task using the affected limb following MPTP. However, the performance of two co-grafted animals demonstrated partial recovery. L-dopa improved operant performance, demonstrating a dopaminergic component to the task. The results demonstrate recovery of behavioral function after surgical treatment, with adrenal co-grafted monkeys showing the greatest degree of improvement.

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Chapter 65 Preliminary report on adrenal medullary grafting and cografting with sural nerve in the treatment of hemiparkinson monkeys

Cited by 29 publications

References 11 publications

Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP‐treated monkeys: Feasibility relevant to multiple‐target grafting as a therapy for Parkinson's disease

Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP‐treated monkeys: Feasibility relevant to multiple‐target grafting as a therapy for Parkinson's disease

Evaluation of animal models of Parkinson's disease for neuroprotective strategies

Behavioral Evaluation of Hemiparkinsonian MPTP Monkeys following Dopamine Pharmacological Manipulation and Adrenal Co-Graft Transplantation

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