Fetal Striatal Transplants in the Ibotenate Lesioned Striatum of Adult Rats: Specific Anatomical Integration between Graft and Host

Abstract

It is well established that grafts of rat fetal striatal tissue, implanted into the excitotoxically lesioned (ibotenic or kainic acid) striatum of adult rats, can ameliorate many of the lesion-induced behavioural deficits (see e.g. Deckel et al, 1983; Isacson et al, 1984, 1986; Sanberg et al, 1986; Dunnett et al, 1988). However, it is still unclear how these transplants exert their functional effects, although several different possible mechanisms have been discussed, e.g. trophic effects on the host brain, neurohumoral release of transmitters, and anatomical integration with the host (see Björklund et al, 1987, for review). In the intact animal, a large number of cortical and subcortical areas (foremost thalamus, substantia nigra, mesencephalic raphe, and amygdala) project densely to the striatum, and the striatum in turn sends its efferents to the globus pallidus, entopeduncular nucleus, and substantia nigra (for review, see Graybiel and Ragsdale, 1983). Fetal striatal tissue implanted into the excitoxically lesioned and thus neuron-depleted striatum, have been shown to develop into striatum-like structures in the lesioned host, both in terms of identified neuronal cell types and their transmitter content (McAllister et al, 1985; Isacson et al, 1985, 1987). Moreover, it has been shown that the host substantia nigra can innervate the grafts (Pritzel et al, 1986; Clarke et al, 1988), and some morphological evidence has been presented to suggest that efferent projections may extend from the implants into the host brain (Pritzel et al, 1986). The existence of projections from the graft to the host has also been suggested in neurochemical studies, i.e. by measured recoveries of GAD enzyme activity (Isacson et al, 1985) and of GABA overflow (Sirinathsinghji et al, 1988) in foremost the globus pallidus of lesioned host rats with intrastriatal implants.