INFLUENCE OF ISCHEMIA AND REPERFUSION ON THE COURSE OF BRAIN-TISSUE SWELLING AND BLOOD-BRAIN-BARRIER PERMEABILITY IN A RODENT MODEL OF TRANSIENT FOCAL CEREBRAL-ISCHEMIA

Brain swelling is a serious complication associated with focal ischemi a in stroke and severe head injury. Experimentally, reperfusion follow ing focal cerebral ischemia exacerbates the level of brain swelling. I n this study, the permeability of the blood-brain barrier has been inv estigated as a possible cause of reperfusion-related acute brain swell ing. Blood-brain barrier disruption was investigated using Evans Blue dye and [C-14]aminoisobutyric acid autoradiography in a rodent model o f reversible middle cerebral artery (RICA) occlusion. Acute brain swel ling and cerebral blood flow (CBF) during ischemia and reperfusion wer e analyzed from double-label CBF autoradiograms after application of t he potent vasoconstrictor peptide endothelin-l to the MCA. Ischemia wa s apparent within ipsilateral MCA territory, 5 min after endothelin-l application to the exposed artery. Reperfusion, examined at 30 min and 1, 2, and 4 h, was gradual but incomplete within this time frame in t he core of middle cerebral artery territory and associated with signif icant brain swelling, Ipsilateral hemispheric swelling increased over time to a maximum (> 5%) at 1-2 h after endothelin-l but was not assoc iated with a significant increase in the ipsilateral transfer constant for [C-14]aminoisobutyric acid over this time frame. These results in dicate that endothelin-l induced focal cerebral ischemia is associated with an acute but reversible hemispheric swelling during the early ph ase of reperfusion which is not associated with a disruption of the bl ood-brain barrier. (C) 1997 Academic Press.