Traumatic brain injury elicits similar alterations in α7 nicotinic receptor density in two different experimental models.
Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. Previous studies have shown alterations in the central cholinergic neurotransmission after TBI. We therefore determined α7 nicotinic acetylcholine receptor (nAChR) densities in newborn piglets and adult rats after experimental TBI. Thirteen newborn piglets (post-TBI survival time: 6 h) underwent fluid percussion (FP) injury (n = 7) or sham operation (n = 6). Furthermore, adult rats randomized into three groups of post-TBI survival times (2, 24, 72 h) received controlled cortical impact injury (CCI, n = 8) or sham operation (n = 8). Brains were frozen, sagittally cut and incubated with the α7-specific radioligand [(125)I]α-bungarotoxin for autoradiography. In injured newborn piglets, decreased α7 receptor densities were observed in the hippocampus (-38%), the hippocampus CA1 (-40%), thalamus (-30%) and colliculus superior (-30%). In adult rats, CCI decreased the receptor densities (between -16 and -47%) in almost any brain region within 2 and 24 h. In conclusion, widespread and significantly lowered α7 nAChR densities were demonstrated in both TBI models. Our results suggest that a nearly similar TBI-induced decrease in the α7 density in the brain of immature and adult animals is found, even with the differences in species, age and experimental procedures. The alterations make the α7 nAChR a suitable target for drug development and neuroimaging after TBI.
Hoffmeister
Peter-Georg
PG
Institute of Radiopharmacy, Research Site Leipzig, Research Center Dresden-Rossendorf, Permoserstraße 15, 04318, Leipzig, Germany.
Donat
Cornelius K
CK
Schuhmann
Martin U
MU
Voigt
Cornelia
C
Walter
Bernd
B
Nieber
Karen
K
Meixensberger
Jürgen
J
Bauer
Reinhard
R
Brust
Peter
P
D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013552:Swine; D055815:Young Adult; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor