Selective cortical neuronal damage after middle cerebral artery occlusion in rats

We studied histopathologic changes in cerebral cortex of 20 rats after middle cerebral artery occlusion by using the Fink-Heimer suppressive silver impregnation method and conventional stains. At 6 hours after occlusion, Fink-Heimer-stained sections revealed abundant coarsely granular, intensely argyrophilic neurons in the ischemic cortex. These distinctive argyrophilic neurons could be clearly differentiated from neurons that suffered postmortem changes; argyrophilic neurons were present in all layers of the lateral parietal cortex but in only the superficial cortical layers II and III in the parasagittal area of the frontoparietal cortex and the temporo-occipital area. At 24 hours after occlusion as the ischemic region progressed to pannecrosis, argyrophilic neurons were still evident in peri-infarct regions, with more prominent neuritic silver deposits but no changes in number or spatial distribution. Over 2-7 days, the argyrophilic neurons gradually disappeared while many fine silver-impregnated degenerating terminals appeared in the peri-infarct regions. At 3-6 weeks after occlusion, no more argyrophilic neurons were seen in the cortex although degenerating axons were still present in the deep white matter. Our results indicate selective neuronal damage in the superficial cortical layers and massive axonal degeneration in the cerebrum surrounding infarcts. The neuronal damage does not appear to progress beyond 6 hours after middle cerebral artery occlusion. The Fink-Heimer method has many advantages over existing conventional stains for documenting selective neuronal damage in focal cerebral ischemia.