Pre-ischemic depletion of brain norepinephrine decreases infarct size in normothermic rats exposed to transient focal cerebral ischemia

This study examined the importance of brain norepinephrine concentration on outcome from a focal ischemic insult. Fasted temperature-controlled male W istar rats pretreated with DSP-4, (N-(chloroethyl)-N-ethyl-2-bromobenzylami ne), to selectively deplete brain norepinephrine, were subjected to reversi ble filament occlusion of the middle cerebral artery for 75 min in the awak e state. After 3 days recovery, total infarct volume in DSP-4 treated rats (185 +/- 107 mm(3)) was reduced vs. untreated control animals (242 +/- 71 m m(3), P = 0.04). Subcortical infarct volume was also smaller in the DSP-4 g roup (93 +/- 44 vs. 121 +/- 28 mm(3), P = 0.02). Cortical infarct volume wa s not statistically different between groups. Neurologic function correlate d with infarct-size. These findings suggest that brain norepinephrine affec ts stroke development either by direct neuronal toxicity and/or through inf luences on the penumbral circulation. Dampening of the central stress respo nse induced by the onset of stroke may thus be advantageous. (C) 1999 Elsev ier Science Ireland Ltd. All rights reserved.