title: Pre-ischemic depletion of brain norepinephrine decreases infarct size in normothermic rats exposed to transient focal cerebral ischemia.
abstract: 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 mm3) was reduced vs. untreated control animals (242 +/- 71 mm3, P = 0.04). Subcortical infarct volume was also smaller in the DSP-4 group (93 +/- 44 vs. 121 +/- 28 mm3, 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.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: B
authors.initials: B
authors.lastname: Nellgård
authors.forename: G B
authors.initials: GB
authors.lastname: Mackensen
authors.forename: S
authors.initials: S
authors.lastname: Sarraf-Yazdi
authors.forename: Y
authors.initials: Y
authors.lastname: Miura
authors.forename: R
authors.initials: R
authors.lastname: Pearlstein
authors.forename: D S
authors.initials: DS
authors.lastname: Warner
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002544:Cerebral Infarction / Q000209:etiology / Q000517:prevention & control*; D004837:Epinephrine / Q000097:blood; D002546:Ischemic Attack, Transient / Q000150:complications / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001596:Benzylamines; D014179:Neurotransmitter Uptake Inhibitors; C012102:DSP 4; D009638:Norepinephrine; D004837:Epinephrine