Changes in mACh, NMDA and GABA(A) receptor binding after lateral fluid-percussion injury: in vitro autoradiography of rat brain frozen sections

Research output: Contribution to journalArticle

Abstract

Adult rats were subjected to a moderate lateral fluid percussion injury (FPI), followed by survival periods of 2 and 12 h. Regional NMDA subtype glutamate, muscarinic acetylcholine and GABA(A) receptor binding in various brain regions was analysed by quantitative in vitro autoradiography and short-lived positron emission tomography tracers [11C]cyano-dizocilpine, 4-N-[11C]methylpiperidylbenzilate (4-N-[11C]MPB), and [11C]flumazenil, respectively. The binding potential (BP, Bmax/KD) was calculated. The data with [11C]cyano-dizocilpine showed a significant decrease in BP bilaterally for the frontoparietal cortex and hippocampus at both time points, in comparison with that of the sham-operated controls. At 12 h the decrease was significantly more prominent for the ipsilateral cortex and hippocampus than for the contralateral side. The BP of 4-N-[11C]MPB was significantly decreased after 2 h for the trauma-side hippocampus, and after 12 h it had decreased for the trauma-site cortex and the bilateral hippocampus. The [11C]flumazenil exhibited a significant decrease in BP for the trauma-site cortex and the underlying hippocampus by 2 h after the traumatic brain injury. After 12 h a significantly decreased BP was observed only for the trauma-site cortex. The finding of a decreased BP demonstrates the involvement of these receptor systems in the development of cellular dysfunction, which is widespread and not limited to the site of lateral FPI.

Details

Authors
  • S Sihver
  • N Marklund
  • L Hillered
  • B Långström
  • Y Watanabe
  • M Bergström
External organisations
  • Uppsala University
Research areas and keywords

Keywords

  • Animals, Autoradiography, Binding Sites, Brain, Brain Injuries, Cerebral Cortex, Dizocilpine Maleate, Flumazenil, Frozen Sections, Hippocampus, Humans, Kinetics, Male, Nitriles, Piperidines, Rats, Rats, Sprague-Dawley, Receptors, GABA-A, Receptors, Muscarinic, Receptors, N-Methyl-D-Aspartate, Tomography, Emission-Computed, Journal Article
Original languageEnglish
Pages (from-to)417-23
JournalJournal of Neurochemistry
Volume78
Issue number3
Publication statusPublished - 2001 Aug
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes