NOREPINEPHRINE AND TRAUMATIC BRAIN INJURY - A POSSIBLE ROLE IN POSTTRAUMATIC EDEMA

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.