Brundin P, Pogarell O, Hagell P, Piccini P, Widner H, Schrag A, Kupsch A, Crabb L, Odin P, Gustavii B, Björklund A, Brooks D J, Marsden C D, Oertel W H, Quinn N P, Rehncrona S, Lindvall O
Section for Neuronal Survival, Division of Neurobiology, Department of Physiological Sciences, Lund University, Sweden.
Brain. 2000 Jul;123 ( Pt 7):1380-90. doi: 10.1093/brain/123.7.1380.
Five parkinsonian patients were transplanted bilaterally into the putamen and caudate nucleus with human embryonic mesencephalic tissue from between seven and nine donors. To increase graft survival, the lipid peroxidation inhibitor tirilazad mesylate was administered to the tissue before implantation and intravenously to the patients for 3 days thereafter. During the second postoperative year, the mean daily L-dopa dose was reduced by 54% and the UPDRS (Unified Parkinson's Disease Rating Scale) motor score in 'off' phase was reduced by a mean of 40%. At 10-23 months after grafting, PET showed a mean 61% increase of 6-L-[(18)F]fluorodopa uptake in the putamen, and 24% increase in the caudate nucleus, compared with preoperative values. No obvious differences in the pattern of motor recovery were observed between these and other previously studied cases with putamen grafts alone. The amount of mesencephalic tissue implanted in each putamen and caudate nucleus was 42 and 50% lower, respectively, compared with previously transplanted patients from our centre. Despite this reduction in grafted tissue, the magnitudes of symptomatic relief and graft survival were very similar. These findings suggest that tirilazad mesylate may improve survival of grafted dopamine neurons in patients, which is in agreement with observations in experimental animals.
五名帕金森病患者双侧接受了来自7至9名供体的人胚胎中脑组织移植到壳核和尾状核。为提高移植物存活率，在植入前向组织中给予脂质过氧化抑制剂甲磺替拉扎特，并在术后3天内静脉给予患者。术后第二年，左旋多巴平均日剂量降低了54%，“关”期的统一帕金森病评定量表（UPDRS）运动评分平均降低了40%。与术前值相比，移植后10 - 23个月，PET显示壳核中6-L-[(18)F]氟多巴摄取平均增加61%，尾状核中增加24%。在这些患者与其他之前仅进行壳核移植的研究病例之间，未观察到运动恢复模式的明显差异。与我们中心之前移植的患者相比，植入每个壳核和尾状核的中脑组织量分别降低了42%和50%。尽管移植组织量减少，但症状缓解程度和移植物存活率非常相似。这些发现表明，甲磺替拉扎特可能会提高患者移植多巴胺神经元的存活率，这与在实验动物中的观察结果一致。
