Fundamental Study on Assessment of Neurotransplantation Using Nuclear Medicine Imaging

阿尔茨海默病是老年人遇到的最棘手的问题之一。一种假说认为，阿尔茨海默病中胆碱能神经传递的缺陷是这种疾病严重症状的基础。大鼠基底大细胞核单侧损伤造成的胆碱能失神经支配模型被报道为认知缺陷模型，是阿尔茨海默病（AD）的指导模型之一。神经移植目前有望作为一种有效的策略来修复各种神经系统疾病，如帕金森病。本研究采用自体迷走神经节移植治疗脑损伤大鼠。术后1、2、4周的放射自显像评价胆碱能移植物对胆碱能系统的影响。用99mtc -六亚甲基-丙烯胺、More肟（99mTc-HMPAO）、[3H]喹乌啶苯磺酸、35s标记的低核苷酸探针分别原位杂交获得脑血流量（CBF）、毒毒碱乙酰胆碱受体（mAChR）、m1和m2亚型AChR-mRNA的图像。用[3H]维萨米醇和[3H]钬-3 （3H- hc -3）获得乙酰胆碱转运体图像。生物成像分析仪采用成像板对自射线图进行定量分析；在受累侧和未受累侧皮层对称设置感兴趣区（roi），并根据这些平均光刺激发光率计算受累侧/未受累侧比值（AU ratio）。在NBM损伤大鼠和自体移植大鼠中，CBF、mAChR、m1mAChR-mRNA和m2mAChR-mRNA图像上的AU比值均无显著变化。另一方面，NBM损伤大鼠的[3H] vesamicol图像显示，损伤后1、2和周的平均AU比显著降低（P<0.01）。自体移植大鼠的平均AU比值在移植后4周逐渐升高并显著改善（p<0.05）。在3H-HC-3处AU比没有明显变化。临床放射放射计算机断层扫描（ECT）与放射性标记的维酰胺可能是一个潜在的程序评估神经移植治疗的AD患者。少

Alzheimer's disease is one of most troublesome problems encountered in the elderly population. One proposed hypothesis is that a deficit in cholinergic neurotransmission in Alzheimer's disease underlies this serious symptom of the disease. Cholinergic denervation rat model by producing an unilateral lesion of nuleus basalis magnocellularis (NBM) are reported to a model of cognitive deficits, one of instructive models of Alzheimer's disease (AD). The neurotransplantation is now promising as an effective strategy for functional repair in a variety of neural systems in disorders such as Parkinson's disease. In this study autotransplantation of vagal ganglion was performed to NBM lesioned rats. The effects of cholinergic grafts on cholinergic systems evaluated by autoradiographic images in duration of 1,2 and 4 weeks after surgery. Cerebral blood flow (CBF), muscarinic acetylcholine receptor (mAChR), m1 and m2 subtype of AChR-mRNA images were obtained using 99mTc-hexamethyl-propyleneamine … More oxime (99mTc-HMPAO), [3H] quinuculidinal benzilate, 35S-labeled oligonucleotide probes by in situ hybridization respectively. Also acetylcholine transporter images were obtained using [3H] vesamicol and [3H] hemicholinium-3 (3H-HC-3). The autoradiograms were quantified by bio-imaging analyzer using imaging plate ; the regions of interesting (ROIs) were set in cortex of the affected side and unaffected side symmetrically, and the affected-side/unaffected-side ratios (AU ratio) were calculated from these mean photo-stimulated luminescence (PSL) rates. In both NBM lesioned and autoransplanted rats, there were no remarkable changes of the AU ratio at CBF,mAChR,m1mAChR-mRNA and m2mAChR-mRNA images. On the other hand, the [3H] vesamicol images of the NBM lesioned rats showed significant reduction of the mean AU ratio at 1,2 and weeks after lesioning (P<0.01). Furthermore, the mean AU ratio in autotransplanted rats gradually increased and significantly improved 4 weeks after transplantation (p<0.05). There were no remarkable changes of the AU ratio at 3H-HC-3. Clinically emission computed tomography (ECT) with radiolabeled vesamicol may be a potential procedure for the assessment of neurotransplantation therapy on patients with AD. Less