Jiang J Y, Lyeth B G, Delahunty T M, Phillips L L, Hamm R J
Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0693.
Brain Res. 1994 Jul 18;651(1-2):123-8. doi: 10.1016/0006-8993(94)90687-4.
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.
实验室研究表明，创伤性脑损伤（TBI）时或损伤后不久毒蕈碱胆碱能受体（mAChRs）的激活显著导致行为发病。最近的研究表明，损伤前用毒蕈碱拮抗剂东莨菪碱治疗可显著减少TBI后11 - 15天的空间记忆缺陷。在本研究中，我们检测了未治疗和经东莨菪碱治疗的大鼠在中度（1.95 atm）液压冲击性TBI后15天脑区的mAChR结合动力学。检测了三组：未治疗的TBI组（n = 8）、损伤前经东莨菪碱治疗（1.0 mg/kg，腹腔注射，损伤前15分钟） 的TBI组（n = 11）和假损伤组（n = 7）。通过[3H]QNB结合测定海马、新皮层和脑干中mAChRs的亲和力（Kd）和最大结合位点数（Bmax）。与假损伤对照组相比，TBI动物海马（4061 +/- 494 fmol/mg蛋白）和新皮层（4272 +/- 640 fmol/mg蛋白）的Bmax值显著更高，但脑干（833 +/- 39 fmol/mg蛋白）无差异（海马：假损伤对照组2812 +/- 218 fmol/mg蛋白；新皮层：2850 +/- 129 fmol/mg蛋白；脑干：794 +/- 26 fmol/mg蛋白）（P < 0.05）。损伤后15天，损伤前经东莨菪碱治疗的TBI动物的mAChRs的Bmax值（海马：2850 +/- 129 fmol/mg蛋白；新皮层：2948 +/- 123 fmol/mg蛋白）与对照组无差异。在所有脑区，各组间Kd值无差异。这些结果表明，TBI可显著改变海马和新皮层中mAChRs的结合位点，且在TBI后长达15天。此外，这些结果表明，一种改善运动和记忆功能结果的药物治疗也使mAChRs生理学方面正常化。这些数据表明，TBI撞击时或撞击后不久mAChRs的过度激活导致TBI的长期病理生理过程。
