Nigrostriatal reconstruction after 6-OHDA lesions in rats: combination of dopamine-rich nigral grafts and nigrostriatal "bridge" grafts.
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.
Dunnett
S B
SB
Department of Experimental Psychology, University of Cambridge, U.K.
Rogers
D C
DC
Richards
S J
SJ
D000818:Animals; D003342:Corpus Striatum / Q000502:physiology / Q000637:transplantation*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004622:Embryo, Mammalian; D005260:Female; D006085:Graft Survival; D006892:Hydroxydopamines; D009498:Neurotoxins; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology / Q000637:transplantation*; D014184:Transplantation, Homologous / Q000379:methods*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D006892:Hydroxydopamines; D009498:Neurotoxins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine