Functional enhancement of intrastriatal dopamine-containing grafts by the co-transplantation of sciatic nerve tissue in 6-hydroxydopamine-lesioned rats

Craig G. van Horne, Ingrid Strömberg, David Young, Lars Olson, Barry Hoffer

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Peripheral nerve "bridges" demonstrate the ability to facilitate axonal growth and regenerate adult and fetal central nervous system tissue. The purpose of this study was to determine if co-grafted peripheral nerve tissue could enhance the ability of fetal dopamine (DA) cell transplants to reinnervate host striatum that had been denervated unilaterally. Male Fisher-344 rats were unilaterally lesioned with 6-hydroxydopamine to eliminate the nigrostriatal DA pathway. A total of 31 rats demonstrated a pattern of rotation indicative of a greater than 98% depletion in DA. Rats were kept as nongrafted controls (n = 6), grafted with sciatic nerve (PN) minces (n = 6), grafted with fetal ventral mesencephalon (VM; n = 10), or co-grafted with VM and PN minces (n = 9). All groups were then tested for changes in apomorphine-induced rotational behavior. The PN control group showed no significant differences in rotation when compared to pregrafting levels and to the lesioned nongrafted group. Both the VM-grafted group and the VM-PN co-grafted group showed significant (P < 0.01, one-way ANOVA) decreases in rotations beginning at 1.5 weeks postgrafting. There was a progressive decrease in rotations up to 12 weeks, the last test point examined. Interestingly, the co-graft group revealed a significantly greater decrease in rotation (P < 0.05) than the VM group beginning at 5 weeks and continuing out to the 12-week test point. Histological and immunocytochemical studies showed good survival of both PN and VM grafts. The augmented recovery could not be accounted for by increased DA cell survival or host brain DA reinnervation in the co-graft group. Taken together, these findings suggest that PN tissue enhances the ability of fetal VM grafts to reinnervate host brain.

Original languageEnglish
Pages (from-to)143-154
Number of pages12
JournalExperimental Neurology
Volume113
Issue number2
DOIs
StatePublished - Aug 1991

Bibliographical note

Funding Information:
TH-positive fibers and nerve terminals were found to grow into PN portions of co-grafts, providing structural evidence for possible interactions of PN and VM tissue. The ability of PN bridge grafts to support the growth of TH positive neurites from VM grafts has been reported previously (1,16). The proposed VM origin of TH-positive fibers in the PN portions of the co-grafts in this study was supported by the absence of TH-positive fibers within PN control grafts. No increase in size of the PN portions of the co-grafts was observed, paralleling the observations in PN grafts alone.

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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