title: Decreased alpha 1-adrenergic receptors after experimental brain injury.
abstract: The magnitude of neuronal damage in central nervous system (CNS) injury may be related, in part, to alterations in the balance between excitatory and inhibitory neurotransmitters. Previous studies have implicated a role of central inhibitory noradrenergic mechanisms in the pathophysiologic sequelae of traumatic brain injury. In the present study, we examined alpha 1-adrenergic receptor binding after parasaggital lateral fluid percussion (FP) brain injury of moderate severity (2.3 atm) in the rat. At 30 min following injury, the specific binding of [3H]prazosin to membranes isolated from left cortex (injury site) was reduced by 37% in brain-injured animals when compared to sham-operated noninjured animals (p < 0.05). However, there were no significant differences in [3H]prazosin binding to membranes of either contralateral (right) cortex or left and right hippocampi between brain-injured and sham-operated animals. Conversely, at 24 h posttrauma, specific binding to membranes of left cortex, cortex adjacent to injury site, contralateral (right) cortex, and left hippocampus was reduced by 25%, 16%, 27%, and 24%, respectively (all p < 0.05). Scatchard analysis revealed that a reduction of [3H]prazosin binding to membranes of injured animals resulted from a decrease in alpha 1-receptor binding density (B-max) but not from changes in ligand affinity. Histopathologic assessment of neuronal damage at 24 h postinjury revealed neuronal loss within injury site cortex and left hippocampus but no clearly discernible cell loss in contralateral right cortex, suggesting that the decrease in B-max might be a consequence of early pathophysiology of trauma rather than of neuronal cell loss. We suggest that alterations in alpha 1-adrenergic receptors after brain injury may result in decreased inhibitory neurotransmitter action of norepinephrine and may thus contribute to the pathophysiology of traumatic brain injury.
authors.affiliation: Department of Surgery, University of Kentucky Medical Center, Lexington.
authors.forename: M R
authors.initials: MR
authors.lastname: Prasad
authors.forename: C M
authors.initials: CM
authors.lastname: Tzigaret
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.forename: H
authors.initials: H
authors.lastname: Soares
authors.forename: T K
authors.initials: TK
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
chemical_list: D011942:Receptors, Adrenergic, alpha; D011224:Prazosin