Lesioning of the striatum reverses motor asymmetry in the 6-hydroxydopamine rodent model of parkinsonism.
In the rat several paradigms of grafting of adrenal medulla into the striatum were studied following the induction of a parkinsonian model, using a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. Direct autologous grafting of adrenal medulla into the caudate-putamen complex, a radiofrequency lesion of the striatum alone, and a radiofrequency lesion followed by delayed grafting of adrenal medulla were compared by analyzing rotational behavior. Direct grafting of adrenal medulla produced an overall reduction in apomorphine induced turning behavior by 43.5% when compared with controls. Radiofrequency lesioning of the striatum without graft showed the best improvement over control animals with a 92% reduction in the total number of rotations induced by apomorphine. Delayed grafting into the caudate lesion cavity also produced a dramatic reduction in motor asymmetry but did not improve the behavioral outcome over that of the lesion alone. Animals receiving only radiofrequency lesions exhibited a band of increased tyrosine hydroxylase like immunoreactivity bordering the lesion cavity. Graft survival was limited in the non-lesioned animals but appeared enhanced in the animals whose striatum was previously lesioned. Lesion location within the striatum influenced the behavioral outcome. Large reductions in apomorphine-induced rotations could result from small lesions of the dorso-lateral striatum. These findings indicate that selective destruction of the caudate-putamen complex without tissue transplantation produces a dramatic reduction in the motor asymmetry of 6-OHDA treated rats. Suggested explanations for the decrease in induced rotational behavior with radiofrequency lesions include a decrease in the number of striatal dopamine receptors following cell destruction and lesion-induced recovery of host dopaminergic afferents. Striatal damage in critical areas can reverse some of the motor behavior associated with the 6-OHDA model and needs to be considered when evaluating the effects of neural grafting in this model.
Department of Neurosurgery, University of Minnesota, Minneapolis 55455.
G M
GM
Friehs
R G
RG
Parker
L S
LS
He
S J
SJ
Haines
D A
DA
Turner
T J
TJ
Ebner
D000313:Adrenal Medulla / Q000637:transplantation; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000503:physiopathology*; D004195:Disease Models, Animal; D006085:Graft Survival / Q000502:physiology; D007150:Immunohistochemistry; D016627:Oxidopamine / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012399:Rotation; D013238:Stereotaxic Techniques; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000201:enzymology; D013563:Sympathectomy, Chemical; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine