BEHAVIORAL-ASSESSMENT OF THE EFFECTS OF EMBRYONIC NIGRAL GRAFTS IN MARMOSETS WITH UNILATERAL 6-OHDA LESIONS OF THE NIGROSTRIATAL PATHWAY

Grafts of embryonic nigral tissue were made into the striatum of marmo sets (Callithrix jacchus) which had previously received a unilateral 6 -hydroxydopamine (6-OHDA) lesion of the nigrostriatal bundle. The graf ts comprised injections of cell suspensions prepared from embryonic (7 4 day) marmoset ventral mesencephalic tissue targeted at multiple stri atal sites in the caudate nucleus, the putamen, and the nucleus accumb ens on the same side as the initial lesion. A series of behavioral tes ts was used to assess the monkeys prior to surgery, following the 6-OH DA lesion, and at regular intervals for 6 months after transplantation surgery. Lesioned and grafted (n = 6) or lesion alone (n = 4) monkeys were matched as far as possible with respect to their scores prior to transplantation so that explicit graft-derived recovery could be dist inguished from any spontaneous recovery that might occur. Sham-lesione d or unoperated monkeys served as further controls (n = 5). The grafts were functionally effective as measured by a reduction, and in some c ases a reversal, of spontaneous, amphetamine- and apomorphine-induced rotation. The reversal of amphetamine-induced rotation correlated with the number of dopaminergic neurons in the grafts visualized by tyrosi ne hydroxylase immunohistochemistry. Successful use of the hands was r estored by the grafts on tasks in which the monkeys reached into tubes to retrieve food. However, functional recovery was not seen on some o ther behavioral tests. In particular, grafts did not influence ipsilat eral biases induced by the lesion, including the position of the head with respect to the rest of the body, hand preference while reaching f or food at a conveyor belt, and neglect of contralateral stimuli eithe r at the conveyor belt or of adhesive labels placed around the feet. I ndeed, the graft group was impaired compared with the lesion group in the accuracy of reaches at the conveyor belt. Overall, these results i ndicate that embryonic nigral grafts can yield a partial recovery from the symptoms induced by unilateral nigrostriatal lesions in a primate model of hemiparkinsonism. (C) 1994 Academic Press, Inc.