Neuroprotective Strategies in Neural Grafting.

The survival of neural grafts is dependent on a multitude of both donor-and host-related conditions. The importance of several of these factors, such as anatomical specificity and age of the donor tissue, surgical technique, immunology, presence of growth factors, and so on, are described in other chapters of this book. The significance of obtaining good survival of neural transplants from a limited source of donor tissue is particularly pertinent when transplanting immature dopamine (DA) neurons. Clinical trials with human embryonic nigral grafts in Parkinson's disease have clearly shown that the implants can provide major symptomatic relief in the patients (Kordower et al., 1996, Kordower et al., 1998; Lindvall, 1997; Tabbal et al., 1998). The success of this therapy is intimately coupled to a significant restoration of striatal DA levels, as evidenced by positron emission tomography scans, and this can only be achieved when there is good transplant survival. Also, in experimental animals with lesions of the nigrostriatal pathway, a clear correlation between the number of surviving dopaminergic (DA-ergic) neurons in grafts and the degree of behavioral restoration has been found (for review, see Brundin et al., 1994). Studies in experimental animals indicate that survival rate of transplanted DA neurons is typically approx 5-15% (Table 1). Neuropathological data from two human transplant cases suggest that the survival rate of grafted DA-ergic neurons in Parkinson's disease patients is in the lower range of this interval (Kordower et al., 1996,Kordower et al., 1998). Table 1Attempts at Enhancing Survival of Grafted Rat DA-ergic Neurons by Different TreatmentsControl (% Survival)Treatment (% Survival)NotesGDNFRosenblad et al., 1996a9.737.4Sinclair et al., 1996b0.78.1Sinclair et al., 1996a1.013.0Granholm et al., 19972.5-fold increaseNo absolute quantificationApostolides et al., 1997a2.41.6FreshApostolides et al., 1997a2.63.4Hibernated 6 dMehtaetal., 1998a1.62.0Hibernated 6 dSautter et al., 1998b5.112.9Yureketal., 1998b1.95.8bFGFMayer et al., 1993a0.91.63-wk survivalMayer et al., 1993 b1.02.79-wk survivalTakayama et al., 1995a6.387.5Takayama et al., 1995b1.520.0Zeng et al., 1996a10.925.0GDNF + bFGF + IGFZawada et al., 19988.212.724-h survivalZawada et al., 19984.16.67-d survivalLazaroidsNakao et al., 1994b15.741.4Grasbon-Frodl et al., 1996bb6.514.0Hibernated 8 dBjörklund et al., 1997b0.92.3Solid grafts in anterior eye chamberKarlsson et al., 1999b6.410.9Calcium antagonists Finger and Dunnett, 1989Increased graft volumeDopamine neurons not quantifiedKaminski Schierle et al., 1999b8.221.5Caspase inhibitors Schierle et al., 1999b1036Figures are either those stated by the respective authors or have been computed based on data presented in the publication based on one of the two following assumptions:aApproximately 8% of the cells in dissected embryonic rat mesencephalic tissue are DA-ergic. These assumptions imply that there are around 400,000 cells obtained from each dissected ventral mesencephalon.bThere are approx 35,000 DA neurons in one rat embryonic mesencephalon. [ABSTRACT FROM AUTHOR]