Nigrostriatal reconstruction after 6-OHDA lesions in rats: combination of dopamine-rich nigral grafts and nigrostriatal "bridge" grafts

Abstract

In an attempt to reconstruct the nigrostriatal dopamine (DA) pathway following 6-hydroxydopamine-induced degeneration in adult rats, a novel double graft procedure has been developed. Embryonic DA-rich grafts were implanted in the vicinity of the host substantia nigra by standard procedures. An intracerebral bridge was then implanted by injection of alternative tissues along a single oblique needle penetration through the frontal pole and neostriatum to the substantia nigra. Embryonic striatal tissue bridges provided a continuous column of tissue from the nigral DA graft to the host striatum. In 3 cases, tyrosine hydroxylase immunoreactive fibres grew the full length of the striatal bridge grafts and were seen to penetrate the host neostriatum. In these three animals alone, methylamphetamine-induced rotation was significantly reduced to 44% of the baseline lesion-induced turning rate. Alternative tissues or substrates (embryonic olfactory bulb, cultured astrocytes or laminin-coated microspheres) were not effective in promoting THir fibre growth from the nigral DA grafts to the host neostriatum.