Intraparenchymal Reaction to the Graft

It has become increasingly clear that the host par-enchymal reaction to the fetal graft is possibly the decisive factor in determining its survival, integration, and functional benefit. Since the early studies with murine models of neurotransplantation, the investigators have suspected that part of the functional benefit may be due to the host reaction to the graft or just to the various surgical procedures (e.g., cavitation). Not surprisingly, prime candidates as mediators of these effects are growth and trophic factors or other molecules produced by the host-reactive neuroglial millieu. The effects of the host-guided migration of donor-derived neurons to selective targets have been convincingly demonstrated. Nonetheless, the opposite may be as important clinically: host sprouting in a dopaminergic graft may be specific and extensive. The most intriguing observations were made in the MPTP model of PD. Bankiewicz and colleagues have demonstrated, in a long-term study of hemiparkinsonian monkeys, that cavitation alone leads to clinical improvement similar to that of autografting dopa-mine-secreting adrenal medullary chromaffin cells. Furthermore, similar results were obtained following implantation of fetal amnion. Both studies suggest strongly that the regenerative capacity of the host brain plays a primary role in functional recovery, at least in this primate model of PD.

Among the most prominent but least understood host reactions to the graft is the microglial response. It is well-known that reactive microglia are important immune mediators as antigen presenting cells infiltrating the grafted tissues. Still, several reports suggest that their presence and less defined activities are critical for the survival of the graft and host brain regeneration. Increasing evidence suggests that microglia are associated not only with pathological but also with normal functions in the brain. Microglia react to injury, usually by responding to and producing NTF. Furthermore, other growth factors produced by microglia, like HGF, were shown to have neurotrophic activities in the CNS. Finally, in a direct experiment, activated macrophages transplanted into a CNS injury site were crucial in triggering a regenerative cascade. In vitro, microglia promote the survival and differentiation of TH-positive neurons, probably through production of NTF or factors like plasminogen that enhance neurite growth. In vivo, nigrostriatal dopaminergic neurons develop neurites around the wound or graft, and this process appears to correlate with the neurotrophic factor production by activated macrophages and microglia.

From this brief summary of the supportive and guidance role played by the surrounding host neuro-glial environment, it has become apparent that neuro-trophic support is crucial in promoting graft survival and differentiation in the host.

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Breaking Bulimia

We have all been there: turning to the refrigerator if feeling lonely or bored or indulging in seconds or thirds if strained. But if you suffer from bulimia, the from time to time urge to overeat is more like an obsession.

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