Norepinephrine and traumatic brain injury: a possible role in post-traumatic edema.
Unilateral cerebral contusion is associated with an early (30 min) increase in norepinephrine (NE) turnover followed by a later (6-24 h) depression of turnover which is bilateral and widespread throughout the brain. Blockade of NE function during the first few hours after traumatic 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 decreased 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 analyzed for NE turnover by HPLC with electrochemical detection. In general, NE turnover (the ratio of 3-methoxy-4-hyroxyphenylglycol to NE levels) had returned to sham-lesion control levels in most brain regions by 2 h after either left or right sided contusions. The only exceptions 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 alpha1-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 which 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 the early increase in NE release following unilateral cerebral contusion is protective and that this may act to stabilize the blood-brain barrier in areas adjacent to the injury site. Drugs that interfere with this enhanced noradrenergic function might enhance the damage caused by TBI.
Neurology Service, (127C) VA Medical Center, East Orange, NJ 07018, USA.
A A
AA
Dunn-Meynell
M
M
Hassanain
B E
BE
Levin
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D001924:Brain Concussion / Q000378:metabolism / Q000503:physiopathology*; D001929:Brain Edema / Q000378:metabolism / Q000503:physiopathology*; D001933:Brain Stem / Q000378:metabolism / Q000503:physiopathology; D002531:Cerebellum / Q000378:metabolism / Q000503:physiopathology; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology; D007213:Indomethacin / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000378:metabolism / Q000503:physiopathology
D000317:Adrenergic alpha-Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; C034674:5-hydroxyindomethacin; D008734:Methoxyhydroxyphenylglycol; D009638:Norepinephrine; D011224:Prazosin; D007213:Indomethacin