Transient global ischemia in rats yields striatal projection neuron and interneuron loss resembling that in Huntington's disease

The various types of striatal projection neurons and interneurons show a di fferential pattern of loss in Huntington's disease (HD). Since striatal inj ury has been suggested to involve similar mechanisms in transient global br ain ischemia and HD, we examined the possibility that the patterns of survi val for striatal neurons after transient global ischemic damage to the stri atum in rats resemble that in HD. The perikarya of specific types of striat al interneurons were identified by histochemical or immunohistochemical lab eling while projection neuron abundance was assessed by cresyl violet stain ing. Projection neuron survival was assessed by neurotransmitter immunolabe ling of their efferent fibers in striatal target areas. The relative surviv al of neuron types was determined quantitatively within the region of ische mic damage, and the degree of fiber loss in striatal target areas was quant ified by computer-assisted image analysis. We found that NADPHd(+) and chol inergic interneurons were largely unaffected, even in the striatal area of maximal damage. Parvalbumin interneurons, however, were as vulnerable as pr ojection neurons. Among immunolabeled striatal projection systems, striatoe ntopeduncular fibers survived global ischemia better than did striatopallid al or striatonigral fibers. The order of vulnerability observed in this stu dy among the striatal projection systems, and the resistance to damage show n by NADPHd(+) and cholinergic interneurons, is similar to that reported in HD. The high vulnerability of projection neurons and parvalbumin interneur ons to global ischemia also resembles that seen in HD. Our results thus ind icate that global ischemic damage to striatum in rat closely mimics HD in i ts neuronal selectivity, which supports the notion that the mechanisms of i njury may be similar in both. (C) 2000 Academic Press.