Abstract TP108: Blood Occludin Level Indicates the Extent of Early Blood Brain Barrier Damage in Ischemic Stroke

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Abstract

Background and Purpose: Fear of symptomatic intracerebral hemorrhage (ICH) has been the primary reason for withholding tPA thrombolysis from acute ischemic stroke patients. Early blood brain barrier (BBB) damage is appreciated to be closely associated with post-thrombolysis ICH, while it remains a technical challenge for rapid assessment of BBB damage before tPA administration. Our recent data showed that cerebral ischemia induced rapid degradation of tight junction protein occludin in ischemic cerebromicrovessels. This study further investigates whether the cleaved occludin is released into the blood stream and how blood occludin levels correlate to the extent of ischemic BBB damage.

Methods: Male Sprague Dawley rats were subjected to 1.5, 3, 4.5, 12 and 24 hours of middle cerebral artery occlusion (MCAO), followed by 5-min reperfusion. Blood samples were taken before and after MCAO. Blood occludin was assessed by ELISA. BBB permeability was measured by Evans blue dye leakage. Occludin cleavage was identified on immunoblots.

Results: MCAO induced Evans blue dye leakage and blood occludin increase in a duration-dependent manner. Blood occludin increase concurrently occurred with the loss of occludin from ischemic cerebral microvessels. Western blot analysis identified two cleaved occludin fragments (31- and 55- kDa) in the blood. Lastly, blood occludin levels remained significantly higher than its basal level within the first 24 hours after MCAO onset.

Conclusions: Our results indicate that blood occludin levels correlate well with the extents of BBB damage and thus may serve as a potential biomarker for evaluating the risk of hemorrhagic transformation before tPA administration.

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