Transplant-induced recovery from 6-OHDA lesions of the nigrostriatal dopamineneurones in mice.

Abstract

Attempts to reconstruct the damaged nigrostriatal pathway in experimental models of Parkinson's disease have thus far been carried out in animals with neurotoxically induced dopamine deficiency. Our study established that unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopamine (DA) neurons produced a well-characterized functional asymmetry in the behaviour of the C57BL/6 (H-2b) mice. The intraperitoneal administration of methamphetamine induced ipsilateral rotation at 7-20 turns/min 1 x 10(6) syngenic DA-rich cells of embryonic ventral mesencephalon were stereotaxically transplanted in the caudate-putamen. A complete recovery of methamphetamine-induced rotational response was produced around the 60th day after the syngenic cell suspension graft. And a complete compensation of the rotational response was also brought about with the DA-rich cells from embryonic ventral mesencephalon (crown-rump length; 10-13 mm) of allogenic C3H/HeN (H-2k) mice. The FACS IV analysis revealed no H-2 (Kk and Iak) antigens before transplantation of these embryonic cells. Immunohistochemistry showed that the dopaminergic fibers had grown predominantly into the ipsilateral caudate-putamen. These results provide evidence of integration of syngenic and allogenic grafts and host tissue. And the immunological response in the transplanted brain are under investigation.