Increased permeability of cerebral vessels to horseradish peroxidase induced by ischemia in Mongolian Gerbils

Abstract

Cerebral ischemia was induced by occlusion of the left common carotic artery in adult Mongolian gerbils. The period of occlusion was 3, 6, or 18 h. Horseradish peroxidase (HRP) was intravenously injected in animals with clear neurological signs 1 h release of the clip. The HRP was allowed to circulate for 5 min. Fixation was carried out by perfusion with aldehydes. Tissue, incubated for peroxidatic activity, from the left side of the brain was treated for electron microscopy. During the postischemic period enhanced permeability was demonstrated in the brains of all animals. The amount of HRP transferred into the neuropil depended on the duration of ischemia. Thus the gerbils with 18 h occlusion showed the greatest content. The cells comprising the neuropil adjacent to vessels were studied and the degree of the pathological changes described below was increased proportionally to the time period of occlusion. The intercellular spaces, often filled with peroxidase, were expanded and the astrocytes swollen, especially the endfeet. Sometimes the astrocytes were pervious to HRP. The neurons were also swollen, but to a lesser degree than the astrocytes. No endothelial cell damage was observed. Even 18 h of occlusion did not change the plasma membranes. The intercellular spaces were free of HRP from the first luminal to the first abluminal tight junction. The cytoplasm exhibited HRP-containing vesicles of various types and shapes. Some were freely situated; others were connected to the plasma membrane and then open to the vessel lumen or to the basement membrane. Since no cell damage was demonstrated, and since no HRP was diffusely dispersed in the cytoplasm it is assumed that vesicles are responsible for the enhancement of the vesicular transport that normally occurs after intravenous injection of HRP.