Long-term cortical atrophy after excitotoxic striatal lesion: Effects of intrastriatal fetal-striatum grafts and implications for Huntington disease

It is not currently clear whether the cortical atrophy observed in Huntingt on disease (HD) is entirely a direct consequence of the disease or at least partially a secondary consequence of striatal atrophy. This is of major im portance for evaluating the possible therapeutic value of intrastriatal fet al-striatum grafts in HD. Cresyl violet-stained sections from rats that had received striatal excitotoxic lesions 1 wk or 4 wk previously showed small and statistically nonsignificant decreases in the thickness of cortical la yers V and VI, while series from rats lesioned 12 months previously showed marked decreases in the thickness of the whole cortex (similar to 35% decre ase), layer V (similar to 45%-50%) and layer VI (similar to 45%-50%), toget her with marked neuron loss in these layers. In deep layer V and layer VI, Fluoro-Jade staining showed labeled neurons in animals lesioned. 1 wk previ ously, labeled neurons and astrocytes in animals lesioned 4 wk previously, and practically no labeling in animals lesioned 12 months previously. Intra cortical injection of Phaseolus vulgaris leucoagglutinin revealed that cort icostriatal fibers were practically absent from the lesioned area of striat a lesioned 12 months previously. However, rats that received intrastriatal fetal-striatum grafts shortly after the lesion and were killed 12 months la ter showed a significant reduction in cortical atrophy, and a large number of labeled corticostriatal fibers surrounding and innervating the graft. In addition, a reduction in the number of Fluoro-Jade-labeled cells in the co rtex was already apparent at 3 wk post-grafting. Regardless of whether HD h as a primary effect on the cortex, the present results suggest that the str iatal degeneration caused by HD contributes markedly to the cortical atroph y, and that intrastriatal grafts may ameliorate this secondary component of the cortical degeneration.