title: Influence of norepinephrine and dopamine on cortical perfusion, EEG activity, extracellular glutamate, and brain edema in rats after controlled cortical impact injury.
abstract: Following traumatic brain injury, catecholamines given to ameliorate cerebral perfusion may induce brain damage via cerebral arteriolar constriction and increased neuronal excitation. In the present study the acute effects of norepinephrine and dopamine on pericontusional cortical perfusion (rCBF), electroencephalographic (EEG) activity, extracellular glutamate, and brain edema were investigated in rats following controlled cortical impact injury (CCI). rCBF, cerebral perfusion pressure (CPP), EEG activity, and glutamate were determined before, during, and after infusing norepinephrine or dopamine, increasing MABP to 120 mm Hg for 90 min at 4 h after CCI. Control rats received physiological saline. At 8 h after CCI, hemispheric swelling and water content were determined gravimetrically. Following CCI, rCBF was significantly decreased. In parallel to elevating MABP and CPP, rCBF was significantly increased by norepinephrine and dopamine, being mostly pronounced with norepinephrine (+44% vs. +29%). In controls, rCBF remained diminished (-45%). EEG activity was significantly increased by norepinephrine and dopamine, while pericontusional glutamate was only elevated by norepinephrine (28 +/- 6 vs. 8 +/- 4 microM). Brain edema was not increased compared to control rats. Despite significantly increasing MABP and CPP to the same extent, norepinephrine and dopamine seem to differentially influence pericontusional cortical perfusion and glutamatergic transmission. In addition to the pressure-passive increase in CPP local cerebral effects seem to account for the sustained norepinephrine-induced increase in pericontusional cortical perfusion. The significantly elevated pericontusional glutamate concentrations in conjunction with the increased EEG activity suggest a sustained metabolically driven increase in cortical perfusion during norepinephrine infusion.
authors.affiliation: Department of Neurosurgery, Charité, Virchow Medical Center, Humboldt University Berlin, Berlin, Germany. skroppen@charite.de
authors.forename: Stefan-Nikolaus
authors.initials: SN
authors.lastname: Kroppenstedt
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Sakowitz
authors.forename: Ulrich-Wilhelm
authors.initials: UW
authors.lastname: Thomale
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Unterberg
authors.forename: John F
authors.initials: JF
authors.lastname: Stover
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D004569:Electroencephalography / Q000187:drug effects*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology
chemical_list: D018698:Glutamic Acid; D004298:Dopamine; D009638:Norepinephrine