(Stroke. 1997;28:2018-2024.)
© 1997 American Heart Association, Inc.
Articles |
Superior Neuroprotective Efficacy of a Novel Antioxidant (U-101033E) With Improved Blood-Brain Barrier Permeability in Focal Cerebral Ischemia
From the Department of Neurosurgery (R.S.-E., S.Z., H.-J.R) and Institute for Surgical Research (E.H., N.P., A.B.), Klinikum Großhadern, Ludwig-Maximilians-University, Munich, Germany.
Correspondence to Dr Robert Schmid-Elsaesser, Department of Neurosurgery, Ludwig Maximilians University, Klinikum Grosshadern, Marchioninistr 15, 81377 Munich, Germany.
Background and Purpose The vascular endothelium and parenchyma of the brain have the potential to generate free radicals under pathological conditions, but it is unclear which of these two sites prevails in the production of free radicals and should be the primary target of therapeutic intervention. To clarify this issue, we compared the neuroprotective properties of a 21-aminosteroid (U-74389G) that acts on the microvasculature and a pyrrolopyrimidine (U-101033E), a novel antioxidant compound that has significantly improved potential to enter the brain parenchyma.
Methods In Sprague-Dawley rats the middle cerebral artery was occluded for 90 minutes by an intraluminal filament. Local cortical blood flow was recorded by bilateral laser Doppler flowmetry throughout ischemia and 1 hour of reperfusion. Three groups of rats were studied: controls that received vehicle only and animals that received either U-74389G or U-101033E. Neurological examinations were performed daily, and infarct size was assessed histologically 7 days after ischemia.
Results U-101033E reduced infarct volume significantly by 51%, whereas U-74389G led to a nonsignificant decrease in infarct volume. U-101033E improved neurological function immediately after ischemia, whereas U-74389G led to improvement only at the end of the observation period. Laser Doppler measurements showed no significant difference in local cortical blood flow among the treatment groups.
Conclusions We conclude that for treatment of transient focal ischemia, an antioxidant that crosses the blood-brain barrier might be superior to agents that predominantly act on the endothelium of the cerebral microvasculature.
Key Words: cerebral ischemia, focal • free radicals • lipid peroxidation • neuroprotection • rats
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