Changes in L1 Antigen Expression in the Rat Striatum After Substantia Nigra Lesions

L1 antigen promotes neurite outgrowth from dopaminergic neurons in tissue culture. In the present study, we examined the effects of dopaminergic deafferentation of the striatum on L1 expression. In the medial-periventricular part of the striatum, both complete and partial substantia nigra (SN) lesions decreased L1 expression. Complete lesions increased L1 expression in the dorso-medial and ventrolateral parts of the striatum on the lesioned side when compared with that on the non-lesioned side. The decrease in the ventro-lateral area was maintained in animals examined three months after the lesioning. Animals with partial SN lesions showed a different pattern of altered L1 expression. After frontal cortex lesions, changes in L1 expression also occur preferentially in the dorso-medial and periventricular striatum. Therefore, the results indicate a complex regulation of L1 expression after damage of striatal circuitry, manifested by a preferential occurrence of changes in periventricular regions

Effects of adrenal medulla grafts on plasma catecholamines and rotational behavior

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 6-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 is 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 increases in plasma catecholamine concentrations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29797/1/0000143.pd

Intracerebral adrenal medulla grafts: A review

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 -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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28322/1/0000078.pd