Unilateral cerebral contusion is associated with an early (30 min) inc
rease in norepinephrine (NE) turnover followed by a later (6-24 h) dep
ression of turnover which is bilateral and widespread throughout the b
rain. Blockade of NE function during the first few hours after traumat
ic brain injury (TBI) impedes subsequent recovery of function without
enlarging the size of the lesion. The current studies were carried out
to characterize further the timing of the switch from increased to de
creased NE turnover and to investigate the pathogenesis of the delayed
recovery of function associated with blocking NE function. Adult male
rats had unilateral somatosensory cortex contusions made with a 5 mm
diameter impact piston. They were killed after 2 h and their brains an
alyzed for NE turnover by HPLC with electrochemical detection. In gene
ral, NE turnover (the ratio of 3-methoxy-4-hyroxyphenylglycol to NE le
vels) had returned to sham-lesion control levels in most brain regions
by 2 h after either left or right sided contusions. The only exceptio
ns were a persistent 87% increase at the lesion site after right-sided
contusions and 22% and 32% increases in the contralateral cerebellum
after right- and left-sided contusions, respectively. Blockade of alph
a(1)-adrenoceptors by treatment with prazosin (3 mg/ kg, i.p.) 30 min
prior to TBI produced edema in the striatum and hippocampus at 24 h wh
ich was not seen saline-treated rats nor in rats where NE reuptake was
blocked with desmethylimipramine (DMI; 10 mg/kg, i.p.). DMI increased
edema at the lesion site at 24 h, however. These data suggest that th
e early increase in NE release following unilateral cerebral contusion
is protective and that this may act to stabilize the blood-brain barr
ier in areas adjacent to the injury site. Drugs that interfere with th
is enhanced noradrenergic function might enhance the damage caused by
TBI. (C) 1998 Elsevier Science B.V. All rights reserved.