Meade C A, Figueredo-Cardenas G, Fusco F, Nowak T S, Pulsinelli W A, Reiner A
Department of Anatomy and Neurobiology, Department of Neurology, University of Tennessee at Memphis, The Health Sciences Center, Memphis, Tennessee, 38163, USA.
Exp Neurol. 2000 Dec;166(2):307-23. doi: 10.1006/exnr.2000.7530.
The various types of striatal projection neurons and interneurons show a differential pattern of loss in Huntington's disease (HD). Since striatal injury has been suggested to involve similar mechanisms in transient global brain ischemia and HD, we examined the possibility that the patterns of survival for striatal neurons after transient global ischemic damage to the striatum in rats resemble that in HD. The perikarya of specific types of striatal interneurons were identified by histochemical or immunohistochemical labeling while projection neuron abundance was assessed by cresyl violet staining. Projectionneuron survival was assessed by neurotransmitter immunolabeling of their efferent fibers in striatal target areas. The relative survival of neuron types was determined quantitatively within the region of ischemic damage, and the degree of fiber loss in striatal target areas was quantified by computer-assisted image analysis. We found that NADPHd(+) and cholinergic interneurons were largely unaffected, even in the striatal area of maximal damage. Parvalbumin interneurons, however, were as vulnerable as projection neurons. Among immunolabeled striatal projection systems, striatoentopeduncular fibers survived global ischemia better than did striatopallidal or striatonigral fibers. The order of vulnerability observed in this study among the striatal projection systems, and the resistance to damage shown by NADPHd(+) and cholinergic interneurons, is similar to that reported in HD. The high vulnerability of projection neurons and parvalbumin interneurons to global ischemia also resembles that seen in HD. Our results thus indicate that global ischemic damage to striatum in rat closely mimics HD in its neuronal selectivity, which supports the notion that the mechanisms of injury may be similar in both.
纹状体的各种投射神经元和中间神经元在亨廷顿舞蹈病（HD）中呈现出不同的损失模式。由于纹状体损伤在短暂性全脑缺血和HD中被认为涉及相似的机制，我们研究了大鼠纹状体短暂性全脑缺血损伤后纹状体神经元的存活模式是否与HD相似的可能性。通过组织化学或免疫组织化学标记来识别特定类型的纹状体中间神经元的胞体，而通过甲酚紫染色评估投射神经元的丰度。通过对其在纹状体靶区的传出纤维进行神经递质免疫标记来评估投射神经元的存活情况。在缺血损伤区域内定量确定神经元类型的相对存活率，并通过计算机辅助图像分析对纹状体靶区的纤维损失程度进行量化。我们发现，即使在损伤最严重的纹状体区域，NADPHd(+)中间神经元和胆碱能中间神经元也基本未受影响。然而，小白蛋白中间神经元与投射神经元一样脆弱。在免疫标记的纹状体投射系统中，纹状体到内苍白球的纤维在全脑缺血后比纹状体到苍白球或纹状体到黑质的纤维存活得更好。本研究中观察到的纹状体投射系统之间的易损性顺序，以及NADPHd(+)中间神经元和胆碱能中间神经元所表现出的抗损伤能力，与HD中报道的情况相似。投射神经元和小白蛋白中间神经元对全脑缺血的高易损性也与HD中所见相似。因此，我们的结果表明，大鼠纹状体的全脑缺血损伤在神经元选择性方面与HD极为相似，这支持了两者损伤机制可能相似的观点。
