Slowly Progressive Neuronal Degeneration in Remote Areas After Focal Cerebral Ischemia

Abstract

Recently, it has become clear that focal cerebral ischemia causes slowly progressive neuropathological changes in certain distant nonischemic areas, such as the ipsilateral thalamus and ipsilateral substantia nigra (SN), remote from the original infarct. In rats, neuronal loss and atrophy were observed in these areas a few weeks after occlusion of the middle cerebral artery (MCA), and an in vitro electrophysiological slice study showed hyperexcitation in the SN neurons. In clinical studies, we have detected secondary changes in the SN using magnetic resonance imaging (MRI) as a high-signal-intensity spot and in the thalamus using computed tomography (CT). However, the mechanism giving rise to these changes is still not clear. For the purpose of interpreting the signal changes on MRI, we attempted to analyze (1) the nigral change by means of MRI and electron microscopy and (2) the changes in water content and capillary permeability in the SN after MCA occlusion in the rat. In the rat, proton density-, T2-, and T1-weighted images were obtained at 1, 4, 7, 14 and 28 days after occlusion of the MCA using a 4.7-T superconductive magnetic resonance (MR) unit. T2-weighted images revealed an area of high signal intensity in the ipsilateral SN at 4 days after occlusion. A low-signal-intensity lesion appeared in the ipsilateral thalamus 7 days after occlusion in proton density- and/or T2-weighted images. Diffusion-weighted images at 4 days after occlusion revealed a high-signal-intensity lesion in the ipsilateral SN. Neuropathological examination showed swelling of perineuronal and perivascular end-feet of astrocytes and also swelling of dendrites. In the ipsilateral SN, no significant change in specific gravity and no demonstrable change in capillary permeability was detected. In the ipsilateral thalamus, there were slight increases in specific gravity, although no change in capillary permeability was demonstrated. In conclusion, we identified two types of secondary neuronal degeneration based on MRI findings, suggesting that secondary degeneration may occur through various mechanisms.