Kerr, Frederick W. L.

The fine structure of the microvasculature in areas of focal cerebral ischemia was studied in squirrel monkeys and the changes in areas of impaired and unimpaired microvascular filling, as defined by carbon perfusion, were compared. Microcirculatory obstruction became evident three hours following middle cerebral artery (MCA) occlusion and appeared to be partly the result of compression of capillaries by perivascular glial swelling and developing cerebral edema. Slight endothelial swelling was a common finding. Intraluminal membrane-bound bodies were occasionally identified but they did not appear to be producing significant obstruction. The tight endothelial junctions remained intact and there was no evidence of accelerated micropinocytosis. Severe neuronal injury frequently preceded the development of the microvascular obstruction and was more widespread than the zones of impaired perfusion.

The sequential synaptic alterations which occur during the early phase of developing cortical infarction in the squirrel monkey were studied with the electron microscope. Mild swelling of a few dendritic terminals and clumping of synaptic vesicles were the earliest detectable changes, being present at 45 minutes. The two basic patterns of degeneration of the terminal boutons were shrinkage and swelling, with shrinkage being the predominant response. Many of the shrunken boutons became electron-dense, resembling the changes present in anterograde axonal degeneration. The alterations which developed in the dendritic terminals were relatively unimpressive. Disruption of axosomatic synapses occurred at an earlier stage and was more severe than that of axodendritic synapses. Reduction in the number of synaptic vesicles was first observed at six hours and appeared to be progressive. The edema which developed was morphologically distinct from both "vasogenic" and "cytotoxic" edema in that there was early and progressive enlargement of the extracellular space.