EFFECTS OF MACROPHAGE-MIGRATION INHIBITORY FACTOR AND MACROPHAGE-MIGRATION STIMULATORY FACTOR ON FUNCTION AND SURVIVAL OF FETAL DOPAMINERGIC GRAFTS IN THE 6-HYDROXYDOPAMINE RAT MODEL OF PARKINSONS-DISEASE

Activated microglia play an important role in the rejection of intrace rebral grafts and the degeneration of axotomized neurones. We studied the effect of macrophage migration stimulatory factor (MSF) or macroph age migration inhibitory factor (MIF) on allogeneic foetal mesencephal ic dopaminergic grafts transplanted into the striatum of 6-hydroxydopa mine-lesioned rats. Rotation testing revealed a significant compensati on of lesion-induced motor asymmetry 3 weeks post-grafting in animals treated with MIF and vehicle-treated controls compared with pre-graft values (Student's t-test, P less than or equal to 0.005) and MSF-treat ed animals (ANOVA, post hoc Fisher PLSD test, P less than or equal to 0.05). The MSF group showed no significant compensation. Graft recipie nts with MIF application (1452.06 +/- 164.32 tyrosine hydroxylase-posi tive ventral mesencephalic cells) and controls (1753.21 +/- 165.51 tyr osine hydroxylase-positive neurones) displayed good graft survival, An imals with MSF application showed a significant reduction of tyrosine hydroxylase-positive grafted cells (MSF 570.36 +/- 209.49 cells) and g raft volumes compared with the MIF and the control group (ANOVA, post hoc Fisher PLSD test, P less than or equal to 0.05). The propotional a rea of microglia was significantly reduced in MIF animals compared wit h control animals (ANOVA, post hoc Fisher PLSD test, P less than or eq ual to 0.001). Activated microglia and macrophages were reduced by hal f in the MIF-treated group compared with MSF animals and controls. We conclude that intrastriatal injections of MSF result in impaired funct ion and survival of allogeneic ventral mesencephalon (VM) grafts 3 wee ks after transplantation. MIF can reduce the number of microglia and m acrophages in allogeneic foetal VM grafts. A reduction of microglia vi a MIF application did not enhance graft function and survival.