The Experts below are selected from a list of 147 Experts worldwide ranked by ideXlab platform
William J. Freed - One of the best experts on this subject based on the ideXlab platform.
-
Effects of Adrenal Medulla grafts on plasma catecholamines and rotational behavior
Experimental Neurology, 1992Co-Authors: Hidetoshi Takashima, Jill B Becker, Maciej Poltorak, William J. FreedAbstract:The mechanisms by which Adrenal Medulla grafts influence the function of host brains in animal models of Parkinson’s disease are unclear. To explore this issue, fragments of Adrenal Medulla or sciatic nerve were transplanted into the lateral ventricle of bilaterally Adrenalectomized (ADX) or sham-ADX rats with unilateral Cl-hydroxydopamine lesions of the substantia nigra. Additional control group received sham-transplantation surgery. Behavioral effects of these procedures were tested following administration of apomorphine, amphetamine, or nicotine. Plasma catecholamines were measured before and after transplantation surgery. In both ADX and sham-ADX rats, Adrenal Medulla grafts produced greater decreases in apomorphine-induced rotational behavior than did sciatic nerve grafts or sham-transplanted groups. Decreases in rotation were smaller in ADX than in sham-ADX animals, regardless of graft treatment. Plasma catecholamines increased after transplantation surgery in each of the sham-ADX groups, regardless of graft type. Increases in plasma dopamine concentrations were associated with decreases in rotational behavior. Five months after transplantation, grafted chromaffin cells demonstrated catecholamine fluorescence, tyrosine hydroxylase (TH) and chromogranin A immunoreactivities, and expression of TH mRNA. It is concluded that Adrenal Medulla grafts produce decreases in apomorphine-induced rotation through a combination of two independent effects. One is a specific effect of Adrenal Medulla grafts. The second is a nonspecific effect that requires an intact Adrenal gland and may be related to
-
Effects of Adrenal Medulla and sciatic nerve co-grafts in rats with unilateral substantia nigra lesions.
Neural Plasticity, 1992Co-Authors: William J. Freed, George Willingham, Robert C. HeimAbstract:Major limitations of Adrenal Medulla transplantation in animal models of Parkinson's disease have been the relatively small behavioral effects and the poor or inconsistent graft survival. Transplantation of fragments of sural nerve in combination with Adrenal Medulla has been reported to increase the survival of chromaffin cells in Adrenal Medulla grafts in primates. In the present study, the possibility was tested that peripheral nerve co-grafts would increase the functional effects of Adrenal Medulla grafts in a 6-hydroxydopamine-lesioned rat model. Animals received unilateral substantia nigra lesions, and subsequently received intraventricular grafts of Adrenal Medulla, sciatic nerve, Adrenal Medulla plus sciatic nerve, or sham grafts consisting of medium only. Functional effects of the grafts were tested using apomorphine-induced rotational behavior. The sciatic nerve co-grafts did not increase the survival of TH-immunoreactive chromaffin cells. The co-grafting treatment also did not augment the overall effect of Adrenal Medulla grafts on rotational behavior. In the animals with substantial numbers of surviving chromaffin cells, however, the animals with sciatic nerve co-grafts showed greater decreases in rotational behavior as compared to the animals with Adrenal Medulla grafts alone, even though the number of surviving cells was not increased.
-
intracerebral Adrenal Medulla grafts a review
Experimental Neurology, 1990Co-Authors: William J. Freed, Maciej Poltorak, Jill B BeckerAbstract:Abstract This review summarizes basic and clinical research on intracerebral Adrenal Medulla grafts, emphasizing potential applications to Parkinson's disease. Properties of intraventricular and intraparenchymal grafts are described, and cell survival and functional effects are compared. It is clear that Adrenal Medulla allografts survive poorly in the parenchyma of the corpus striatum and better in the lateral ventricle. Nerve growth factor (NGF) may improve the survival of Adrenal Medulla grafts. In the absence of added NGF even Adrenal Medulla grafts in the ventricle survive irregularly, and the factors required for graft survival in the ventricle are not well understood. In the 6-hydroxydopamine-lesioned rat model most evidence suggests, not surprisingly, that Adrenal Medulla grafts produce functional effects only when they survive. These effects may be related to production of catecholamines by the transplanted cells. In addition, Adrenal Medulla grafts may produce trophic effects on host brain. These effects are most evident in animals with MPTP-induced damage to dopaminergic systems and may be nonspecific, possibly related in part to the brain injury that is induced by graft implantation. Trophic effects may contribute to the functional effects of Adrenal Medulla grafts: For intraparenchymal grafts, trophic effects that do not require cell survival may contribute small functional changes, while additional behavioral effects may require substantial chromaffin cell survival. The evidence for direct dopamine-mediated effects as compared to trophic mechanisms of action for these grafts in animal models for Parkinson's disease is presented. Clinical studies of Adrenal Medulla grafts in human patients are examined and compared in detail. When inspected closely, the various clinical studies are in general agreement on most points, although there are differences in the degree of improvement found, both across different studies and individual patients. It is concluded that some beneficial clinical effects occur, with small to modest changes in most patients and substantial improvement in a minority of patients. There also seem to be larger or more consistent changes in durations of “on” and “off” times in l -dihydroxyphenylalanine-treated patients. There are substantial side effects, and it is not clear that the clinical changes are sufficient to justify performing Adrenal Medulla transplantation in human patients as a routine procedure. The findings of clinical studies are generally consistent with the predictions that would have been made from animal studies; however, it is not clear whether some of the clinical effects could be nonspecific consequences of lesioning or surgery. Additional basic research would be required to develop a consistently effective clinical procedure. Remaining unanswered questions include the relative contributions of dopamine production and trophic changes to the functional effects of Adrenal Medulla grafts, the factors required for Adrenal Medulla graft survival, and the factors responsible for the substantial improvement that has been seen in some patients. The review concludes with a series of recommendations for future basic and clinical research on Adrenal Medulla transplantation.
-
Adrenal Medulla graft induced recovery of function in an animal model of Parkinson's disease: possible mechanisms of action.
Canadian Journal of Psychology\ revue Canadienne De Psychologie, 1990Co-Authors: Jill B Becker, Eileen J. Curran, William J. FreedAbstract:Following unilateral dopamine (DA) denervation of the striatum in animals, there is an asymmetry in the striatal DA system. Animals with such denervations will rotate vigorously when given dopaminergic drugs. Adrenal Medulla grafts placed in the lateral ventricle adjacent to a DA-denervated striatum decrease rotational behaviour induced by DA receptor agonists or DA-releasing agents. This discussion reviews research on the use of Adrenal Medulla grafts to reverse behavioural deficits following DA-denervation of the striatum. Results from basic animal research and from the application of the procedure to patients with Parkinson's disease suggests that at least three different fundamental processes may mediate the functional effects of Adrenal Medulla grafts: (a) Adrenal Medulla grafts may induce changes in the blood-brain barrier; (b) Adrenal Medulla grafts may induce an increase in serum DA; and (c) Adrenal Medulla grafts may have a trophic effect on the host brain. Hypotheses are proposed to explain the behavioural effects of Adrenal Medulla grafts in light of the processes that are thought to mediate their effects.
Jill B Becker - One of the best experts on this subject based on the ideXlab platform.
-
Effects of Adrenal Medulla grafts on plasma catecholamines and rotational behavior
Experimental Neurology, 1992Co-Authors: Hidetoshi Takashima, Jill B Becker, Maciej Poltorak, William J. FreedAbstract:The mechanisms by which Adrenal Medulla grafts influence the function of host brains in animal models of Parkinson’s disease are unclear. To explore this issue, fragments of Adrenal Medulla or sciatic nerve were transplanted into the lateral ventricle of bilaterally Adrenalectomized (ADX) or sham-ADX rats with unilateral Cl-hydroxydopamine lesions of the substantia nigra. Additional control group received sham-transplantation surgery. Behavioral effects of these procedures were tested following administration of apomorphine, amphetamine, or nicotine. Plasma catecholamines were measured before and after transplantation surgery. In both ADX and sham-ADX rats, Adrenal Medulla grafts produced greater decreases in apomorphine-induced rotational behavior than did sciatic nerve grafts or sham-transplanted groups. Decreases in rotation were smaller in ADX than in sham-ADX animals, regardless of graft treatment. Plasma catecholamines increased after transplantation surgery in each of the sham-ADX groups, regardless of graft type. Increases in plasma dopamine concentrations were associated with decreases in rotational behavior. Five months after transplantation, grafted chromaffin cells demonstrated catecholamine fluorescence, tyrosine hydroxylase (TH) and chromogranin A immunoreactivities, and expression of TH mRNA. It is concluded that Adrenal Medulla grafts produce decreases in apomorphine-induced rotation through a combination of two independent effects. One is a specific effect of Adrenal Medulla grafts. The second is a nonspecific effect that requires an intact Adrenal gland and may be related to
-
intracerebral Adrenal Medulla grafts a review
Experimental Neurology, 1990Co-Authors: William J. Freed, Maciej Poltorak, Jill B BeckerAbstract:Abstract This review summarizes basic and clinical research on intracerebral Adrenal Medulla grafts, emphasizing potential applications to Parkinson's disease. Properties of intraventricular and intraparenchymal grafts are described, and cell survival and functional effects are compared. It is clear that Adrenal Medulla allografts survive poorly in the parenchyma of the corpus striatum and better in the lateral ventricle. Nerve growth factor (NGF) may improve the survival of Adrenal Medulla grafts. In the absence of added NGF even Adrenal Medulla grafts in the ventricle survive irregularly, and the factors required for graft survival in the ventricle are not well understood. In the 6-hydroxydopamine-lesioned rat model most evidence suggests, not surprisingly, that Adrenal Medulla grafts produce functional effects only when they survive. These effects may be related to production of catecholamines by the transplanted cells. In addition, Adrenal Medulla grafts may produce trophic effects on host brain. These effects are most evident in animals with MPTP-induced damage to dopaminergic systems and may be nonspecific, possibly related in part to the brain injury that is induced by graft implantation. Trophic effects may contribute to the functional effects of Adrenal Medulla grafts: For intraparenchymal grafts, trophic effects that do not require cell survival may contribute small functional changes, while additional behavioral effects may require substantial chromaffin cell survival. The evidence for direct dopamine-mediated effects as compared to trophic mechanisms of action for these grafts in animal models for Parkinson's disease is presented. Clinical studies of Adrenal Medulla grafts in human patients are examined and compared in detail. When inspected closely, the various clinical studies are in general agreement on most points, although there are differences in the degree of improvement found, both across different studies and individual patients. It is concluded that some beneficial clinical effects occur, with small to modest changes in most patients and substantial improvement in a minority of patients. There also seem to be larger or more consistent changes in durations of “on” and “off” times in l -dihydroxyphenylalanine-treated patients. There are substantial side effects, and it is not clear that the clinical changes are sufficient to justify performing Adrenal Medulla transplantation in human patients as a routine procedure. The findings of clinical studies are generally consistent with the predictions that would have been made from animal studies; however, it is not clear whether some of the clinical effects could be nonspecific consequences of lesioning or surgery. Additional basic research would be required to develop a consistently effective clinical procedure. Remaining unanswered questions include the relative contributions of dopamine production and trophic changes to the functional effects of Adrenal Medulla grafts, the factors required for Adrenal Medulla graft survival, and the factors responsible for the substantial improvement that has been seen in some patients. The review concludes with a series of recommendations for future basic and clinical research on Adrenal Medulla transplantation.
-
Adrenal Medulla graft induced recovery of function in an animal model of Parkinson's disease: possible mechanisms of action.
Canadian Journal of Psychology\ revue Canadienne De Psychologie, 1990Co-Authors: Jill B Becker, Eileen J. Curran, William J. FreedAbstract:Following unilateral dopamine (DA) denervation of the striatum in animals, there is an asymmetry in the striatal DA system. Animals with such denervations will rotate vigorously when given dopaminergic drugs. Adrenal Medulla grafts placed in the lateral ventricle adjacent to a DA-denervated striatum decrease rotational behaviour induced by DA receptor agonists or DA-releasing agents. This discussion reviews research on the use of Adrenal Medulla grafts to reverse behavioural deficits following DA-denervation of the striatum. Results from basic animal research and from the application of the procedure to patients with Parkinson's disease suggests that at least three different fundamental processes may mediate the functional effects of Adrenal Medulla grafts: (a) Adrenal Medulla grafts may induce changes in the blood-brain barrier; (b) Adrenal Medulla grafts may induce an increase in serum DA; and (c) Adrenal Medulla grafts may have a trophic effect on the host brain. Hypotheses are proposed to explain the behavioural effects of Adrenal Medulla grafts in light of the processes that are thought to mediate their effects.
Agneta Nordberg - One of the best experts on this subject based on the ideXlab platform.
-
expression of nicotinic acetylcholine receptors in human and rat Adrenal Medulla
Life Sciences, 2001Co-Authors: Malahat Mousavi, Ewa Hellstromlindahl, Zhizhong Guan, I Bednar, Agneta NordbergAbstract:Abstract Neuronal nicotinic receptors (nAChRs) are expressed in the brain but also in the peripheral tissues including the Adrenal Medulla. However, it is unclear which nAChRs are present in the human Adrenal Medulla. In the study, receptor binding assay, Western blot and RT-PCR have been performed to investigate the expression of nAChRs in Adrenal Medulla from human, rat and mouse. The results showed that in human adult Adrenal Medulla, mRNAs for nAChR α3, α4, α5, α7, β2, β3, and β4 subunits but not β2 in the fetal human Adrenal Medulla were expressed. Saturation binding of [ 3 H]epibatidine showed two binding sites in human aged Adrenal Medulla. The specific binding of [ 3 H]epibatidine (0.1 nM) was significantly higher in human fetal compared to human aged Adrenal Medulla. mRNAs for the α3, α4, α5, α7, β2, and β4 subunits but not the β3 were detectable in adult rat and mouse Adrenal Medulla. No differences in gene-expression of the nAChRs were observed between new born, adult and aged rat Adrenal Medulla. Saturation binding of [ 3 H]epibatidine showed only one binding site in rat Adrenal Medulla. Lower protein levels for the nAChR subunits were observed in the rat Adrenal Medulla compared to rat brain. There was lower protein levels of the nAChRs in aged rat Adrenal Medulla compared to the young rats. Sub-chronic treatment of nicotine to rats did not influence level of the nAChRs in the Adrenal Medulla. In conclusion, the expression of nAChRs in Adrenal Medulla is age- related and species dependent.
Maciej Poltorak - One of the best experts on this subject based on the ideXlab platform.
-
Effects of Adrenal Medulla grafts on plasma catecholamines and rotational behavior
Experimental Neurology, 1992Co-Authors: Hidetoshi Takashima, Jill B Becker, Maciej Poltorak, William J. FreedAbstract:The mechanisms by which Adrenal Medulla grafts influence the function of host brains in animal models of Parkinson’s disease are unclear. To explore this issue, fragments of Adrenal Medulla or sciatic nerve were transplanted into the lateral ventricle of bilaterally Adrenalectomized (ADX) or sham-ADX rats with unilateral Cl-hydroxydopamine lesions of the substantia nigra. Additional control group received sham-transplantation surgery. Behavioral effects of these procedures were tested following administration of apomorphine, amphetamine, or nicotine. Plasma catecholamines were measured before and after transplantation surgery. In both ADX and sham-ADX rats, Adrenal Medulla grafts produced greater decreases in apomorphine-induced rotational behavior than did sciatic nerve grafts or sham-transplanted groups. Decreases in rotation were smaller in ADX than in sham-ADX animals, regardless of graft treatment. Plasma catecholamines increased after transplantation surgery in each of the sham-ADX groups, regardless of graft type. Increases in plasma dopamine concentrations were associated with decreases in rotational behavior. Five months after transplantation, grafted chromaffin cells demonstrated catecholamine fluorescence, tyrosine hydroxylase (TH) and chromogranin A immunoreactivities, and expression of TH mRNA. It is concluded that Adrenal Medulla grafts produce decreases in apomorphine-induced rotation through a combination of two independent effects. One is a specific effect of Adrenal Medulla grafts. The second is a nonspecific effect that requires an intact Adrenal gland and may be related to
-
intracerebral Adrenal Medulla grafts a review
Experimental Neurology, 1990Co-Authors: William J. Freed, Maciej Poltorak, Jill B BeckerAbstract:Abstract This review summarizes basic and clinical research on intracerebral Adrenal Medulla grafts, emphasizing potential applications to Parkinson's disease. Properties of intraventricular and intraparenchymal grafts are described, and cell survival and functional effects are compared. It is clear that Adrenal Medulla allografts survive poorly in the parenchyma of the corpus striatum and better in the lateral ventricle. Nerve growth factor (NGF) may improve the survival of Adrenal Medulla grafts. In the absence of added NGF even Adrenal Medulla grafts in the ventricle survive irregularly, and the factors required for graft survival in the ventricle are not well understood. In the 6-hydroxydopamine-lesioned rat model most evidence suggests, not surprisingly, that Adrenal Medulla grafts produce functional effects only when they survive. These effects may be related to production of catecholamines by the transplanted cells. In addition, Adrenal Medulla grafts may produce trophic effects on host brain. These effects are most evident in animals with MPTP-induced damage to dopaminergic systems and may be nonspecific, possibly related in part to the brain injury that is induced by graft implantation. Trophic effects may contribute to the functional effects of Adrenal Medulla grafts: For intraparenchymal grafts, trophic effects that do not require cell survival may contribute small functional changes, while additional behavioral effects may require substantial chromaffin cell survival. The evidence for direct dopamine-mediated effects as compared to trophic mechanisms of action for these grafts in animal models for Parkinson's disease is presented. Clinical studies of Adrenal Medulla grafts in human patients are examined and compared in detail. When inspected closely, the various clinical studies are in general agreement on most points, although there are differences in the degree of improvement found, both across different studies and individual patients. It is concluded that some beneficial clinical effects occur, with small to modest changes in most patients and substantial improvement in a minority of patients. There also seem to be larger or more consistent changes in durations of “on” and “off” times in l -dihydroxyphenylalanine-treated patients. There are substantial side effects, and it is not clear that the clinical changes are sufficient to justify performing Adrenal Medulla transplantation in human patients as a routine procedure. The findings of clinical studies are generally consistent with the predictions that would have been made from animal studies; however, it is not clear whether some of the clinical effects could be nonspecific consequences of lesioning or surgery. Additional basic research would be required to develop a consistently effective clinical procedure. Remaining unanswered questions include the relative contributions of dopamine production and trophic changes to the functional effects of Adrenal Medulla grafts, the factors required for Adrenal Medulla graft survival, and the factors responsible for the substantial improvement that has been seen in some patients. The review concludes with a series of recommendations for future basic and clinical research on Adrenal Medulla transplantation.
Malahat Mousavi - One of the best experts on this subject based on the ideXlab platform.
-
expression of nicotinic acetylcholine receptors in human and rat Adrenal Medulla
Life Sciences, 2001Co-Authors: Malahat Mousavi, Ewa Hellstromlindahl, Zhizhong Guan, I Bednar, Agneta NordbergAbstract:Abstract Neuronal nicotinic receptors (nAChRs) are expressed in the brain but also in the peripheral tissues including the Adrenal Medulla. However, it is unclear which nAChRs are present in the human Adrenal Medulla. In the study, receptor binding assay, Western blot and RT-PCR have been performed to investigate the expression of nAChRs in Adrenal Medulla from human, rat and mouse. The results showed that in human adult Adrenal Medulla, mRNAs for nAChR α3, α4, α5, α7, β2, β3, and β4 subunits but not β2 in the fetal human Adrenal Medulla were expressed. Saturation binding of [ 3 H]epibatidine showed two binding sites in human aged Adrenal Medulla. The specific binding of [ 3 H]epibatidine (0.1 nM) was significantly higher in human fetal compared to human aged Adrenal Medulla. mRNAs for the α3, α4, α5, α7, β2, and β4 subunits but not the β3 were detectable in adult rat and mouse Adrenal Medulla. No differences in gene-expression of the nAChRs were observed between new born, adult and aged rat Adrenal Medulla. Saturation binding of [ 3 H]epibatidine showed only one binding site in rat Adrenal Medulla. Lower protein levels for the nAChR subunits were observed in the rat Adrenal Medulla compared to rat brain. There was lower protein levels of the nAChRs in aged rat Adrenal Medulla compared to the young rats. Sub-chronic treatment of nicotine to rats did not influence level of the nAChRs in the Adrenal Medulla. In conclusion, the expression of nAChRs in Adrenal Medulla is age- related and species dependent.