Differential passage of [14C]sucrose and [3H]inulin across rat blood-brain barrier after cerebral ischemia

Abstract

The biophysical nature of blood-brain barrier (BBB) opening after ischemic or hemorrhagic stroke or traumatic brain injury is unresolved. Ultrastructural (electron micrograph) investigations of experimental BBB injury commonly indicate the abnormal presence of vesicles or tubular structures in cerebrovascular endothelial cells, suggesting the likelihood of convective, fluid-phase transport of blood substances into brain. We measured transfer constants (K(i)s) for the simultaneous passage of two intravenously delivered tracers ([14C]sucrose, mol wt=342; [3H]inulin approximately 5,000) across the intact BBB in the rat, and 24 h after global cerebral ischemia (16-20 min duration) or 24, 48 or 72 h after focal ischemia (2 h duration). In both ischemia models, the upward increment in K(i) (DeltaK(i)) for sucrose, indicating the extra injury-related tracer flux into brain, significantly exceeded that for inulin, as might be expected with faster diffusion of the smaller molecule through injury pores or channels. This inequality of DeltaK(i)s did not suggest a major role for convective, fluid-phase transport by endothelial vesicular or tubular structures and a predominance of diffusional transport was indicated.