Selective, Delayed Increase in Transfer Constants for Cerebrovascular Permeation of Blood-Borne ³H-Sucrose Following Forebrain Ischaemia in the Rat

Summary

Experiments were conducted to explore the time course of changes in blood-brain barrier (BBB) permeability that may occur in the 2-vessel occlusion model of stroke in the rat. Anaesthetized Sprague-Dawley rats underwent 10 min of cerebral ischaemia produced by bilateral carotid occlusion plus haemorrhagic hypotension. After 6 min, or 3, 6, 18, 24, 48 h recovery and re-anaesthetization, an i.v. injection of ³H-sucrose was permitted to circulate for 30 min. Regional transfer constants (Ki) for BBB permeation of sucrose were calculated from the ratio of sucrose concentration in parenchyma relative to the time-integrated plasma concentration. In the 6-min group, all cerebral regions showed evidence of early BBB leakiness (increase in Ki above non-stroke baseline) which was maximal in forebrain cortex. This effect was diminished at subsequent time points, except in striatum and hippocampus which exhibited delayed intensification of opening, maximal in the 6 h group. Ki values had largely normalized by 24 h. Ki values were also determined 6 min, 6 h and 24 h after a 20-min stroke procedure. Early and regionally selective, delayed BBB openings were also seen, but recovery was not evident in cerebral regions at 24 h. Cortex exhibited a large increase in Ki indicating that a delayed, marked deterioration of BBB integrity had developed between the 6 h and 24 h time points. It is concluded that the combination of transfer constant measurements and the 2-vessel occlusion model could provide a sensitive means for investigating the cerebrovascular consequences and therapy of stroke.