A new approach to the integrity of dual blood-brain barrier functions of global ischemic rats. Barrier and carrier functions.

Abstract

We studied the influence of reperfusion on carrier and barrier functions of the blood-brain barrier after transient global ischemia in rats. We used iodine-125-labeled 3-iodo-alpha-methyl-L-tyrosine and carbon-14-labeled sucrose as tracers for studying carrier and barrier functions of the blood-brain barrier, respectively. Brain uptakes of these two tracers were measured in Wistar rats subjected to either 15- or 30-minute four-vessel occlusion developed by Pulsinelli and Brierly before recirculation for 3, 6, 24, 48, and 72 hours. Tracer (5 microCi) was injected intravenously in each rat 30 minutes before killing the animal. Following 15- or 30-minute ischemia, [14C]sucrose uptakes were significantly higher at 3 and 6 hours of reperfusion before recovery to control values after reperfusing for 24 to 48 hours in almost all brain regions. However, a rebound in radioligand uptake was significantly manifested in some sites at 72 hours after reperfusion (p < 0.05 to p < 0.01). Uptakes of 125I-3-iodo-alpha-methyl-L-tyrosine were brain site-dependent: significantly (p < 0.05) higher in cortex (3 and 48 hours after reperfusion) and thalamus (3, 6, and 48 hours after reperfusion) but significantly (p < 0.05 to p < 0.01) lower in striatum, cortex (72 hours after reperfusion), and midbrain (6, 24, and 72 hours after reperfusion). Because the [14C]sucrose uptake in brain was 10% lower than that of 125I-3-iodo-alpha-methyl-L-tyrosine, the change in absolute transport of the latter tracer was approximated to its brain uptake. The carrier and barrier functions of the blood-brain barrier should be evaluated separately. The radioligand 125I-3-iodo-alpha-methyl-L-tyrosine may serve as a useful tool to evaluate the carrier function of the blood-brain barrier after transient cerebral ischemia in rats.