Effect of intracerebral norepinephrine depletion on outcome from severe forebrain ischemia in the rat

Manipulations of plasma catecholamine concentrations influence outcome from ischemic brain insults. It has been suggested that these effects are media ted by influences on brain catecholamine concentrations. This study examine d whether major changes in brain norepinephrine concentrations can alter ou tcome from severe forebrain ischemia. Sprague-Dawley rats were administered 50 mg/kg i.p. N-(chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) or were l eft untreated (control). One week later, these rats were subjected to eithe r 7 or 8 min of normothermic forebrain ischemia (bilateral carotid occlusio n and MABP = 30 mmHg) and allowed to recover for 4 days. Histologic damage was then evaluated. In other control and DSP-4-treated animals, hippocampal microdialysate norepinephrine concentrations were measured before, during and after 8 min of forebrain ischemia. Norepinephrine concentrations were a lso determined in brain homogenates from non-ischemic DSP-treated and contr ol rats. A 95% depletion of norepinephrine was observed in brain homogenate s from non-ischemic DSP-4-treated rats compared with control. During ischem ia, microdialysate norepinephrine concentrations increased in control but n ot in DSP-4-treated rats (P = 0.002). For plasma, intra-ischemic epinephrin e concentrations increased 8-10-fold and returned to baseline values post-i schemia with no differences between groups. Plasma norepinephrine values re mained unchanged in both groups. Histologic damage resulting from either 7 or 8 min of ischemia in hippocampal structures, caudoputamen, and neocortex was similar between DSP-4-treated and control groups. This study could not identify any effect of major changes in brain norepinephrine concentration s on ischemic brain damage. These data indicate that peripheral catecholami ne effects on near-complete forebrain ischemic outcome are unlikely to be m ediated by effects on central catecholamine concentrations. (C) 1999 Elsevi er Science B.V. All rights reserved.