Muscarinic cholinergic receptor binding in rat brain at 15 days following traumatic brain injury.
Laboratory studies indicate that activation of muscarinic cholinergic receptors (mAChRs) at or soon after traumatic brain injury (TBI) significantly contributes to behavioral morbidity. Recent research has demonstrated that pre-injury treatment with the muscarinic antagonist scopolamine significantly reduces spatial memory deficits at 11-15 days post-TBI. In the present study, we examined mAChR binding kinetics in brain regions at 15 days after moderate (1.95 atm) fluid percussion TBI in untreated and scopolamine-treated rats. Three groups were examined: untreated TBI (n = 8), TBI with pre-injury scopolamine treatment (1.0 mg/kg, i.p., 15 min prior to injury) (n = 11), and sham-injury (n = 7). The affinity (Kd) and maximum number of binding sites (Bmax) of mAChRs in hippocampus, neocortex, and brainstem were determined by [3H]QNB binding. Bmax values in TBI animals were significantly higher in hippocampus (4061 +/- 494 fmol/mg protein) and neocortex (4272 +/- 640 fmol/mg protein), but not in brainstem (833 +/- 39 fmol/mg protein) compared to sham-injured controls (hipp. 2812 +/- 218 fmol/mg/protein; neoctx. 2850 +/- 129 fmol/mg protein; brainstem 794 +/- 26 fmol/mg protein) (P < 0.05). At 15 days after injury, Bmax values of mAChRs in TBI animals with pre-injury scopolamine treatment (hipp. 2850 +/- 129 fmol/mg protein; neoctx. 2948 +/- 123 fmol/mg protein) did not differ from control. In all brain regions, Kd values did not differ between groups. These results demonstrate that TBI significantly alters the binding sites of mAChRs in hippocampus and neocortex for as long as 15 days after TBI. Furthermore, these results indicate that a pharmacological treatment that improves motor and memory function outcome also normalizes aspects of mAChRs physiology. These data suggest that excessive activation of mAChRs at or soon after TBI impact contributes to long-term pathophysiological processes in TBI.
Jiang
J Y
JY
Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0693.
Lyeth
B G
BG
Delahunty
T M
TM
Phillips
L L
LL
Hamm
R J
RJ
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013997:Time Factors
D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate