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 Wistar rats pretreated with DSP-4, (N-(chloroethyl)-N-ethyl-2-bromobenzylamine), to selectively deplete brain norepinephrine, were subjected to reversible filament occlusion of the middle cerebral artery for 75 min in the awake 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 mm(3), P = 0.04). Subcortical infarct volume was also smaller in the DSP-4 group (93 +/- 44 vs. 121 +/- 28 mm(3), P = 0.02). Cortical infarct volume was not statistically different between groups. Neurologic function correlated with infarct-size. These findings suggest that brain norepinephrine affects stroke development either by direct neuronal toxicity and/or through influences on the penumbral circulation. Dampening of the central stress response induced by the onset of stroke may thus be advantageous. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.