Real-time Estimation of Mannitol-Induced Blood-Brain-Barrier Disruption by Microdialysis

ABSTRACT

We have done a study for the real-time changes of blood-brain-barrier disruption(BBBD) with brain cortical microdialysis induced by intra-carotid mannitol infusion and of cortical blood flow with laser Doppler flowmetry. A microdialysis probe was established on the right parietal cortex with 99mTc-DTPA(500 Da) as a marker, and two laser Doppler probes on the bilateral frontal cortex. Intra-carotid administration of mannitol was followed in 3 rats and intra-arterial infusion of isotonic saline in 3 control rats. Cortical blood flows were increased dramatically by about 270% to 310% from the preinfusion state within 5 minutes after mannitol infusion as compared to an average of 150% increase in saline controls. BBBd-induced extravascular leakage of 99mTc-DTPA sampled by microdialysis and estimated by high pressure liquid chromatography increased dramatically within 2 minutes, maximally about 10 times that of the pre-infusion state within 5-10 minutes after infusion, and decreased rapidly about next 20 minutes but was still more than 4 times the pre-infusion state, and slowed to near preinfusion state during the next 40-60 minutes. This result suggests the real changes of BBBD estimated by brain cortical microdialysis were relatively comparable to previous radioisotope measurement and the first 20 minutes was significantly valuable for administration of certain molecules using BBBD induced by intra-arterial mannitol infusion.