Changes in mACh, NMDA and GABA(A) receptor binding after lateral fluid-percussion injury: in vitro autoradiography of rat brain frozen sections.
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.
Sihver
S
S
Department of Neuroscience, Unit of Pharmacology, Faculty of Medicine, University of Uppsala, Uppsala, Sweden.
Marklund
N
N
Hillered
L
L
Långström
B
B
Watanabe
Y
Y
Bergström
M
M
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000031:analogs & derivatives / Q000378:metabolism; D005442:Flumazenil; D005629:Frozen Sections; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D009570:Nitriles / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D009570:Nitriles; D010880:Piperidines; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; C433774:cyano-diczocilpine; C433775:methylpiperidylbenzilate; D005442:Flumazenil; D016291:Dizocilpine Maleate