Pike B R, Hamm R J
Department of Psychology, Virginia Commonwealth University, Richmond 23284-2018, USA.
Pharmacol Biochem Behav. 1997 Aug;57(4):785-91. doi: 10.1016/s0091-3057(96)00453-4.
Cognitive impairment after traumatic brain injury (TBI) is correlated with decreased cholinergic markers of neuronal viability. The purpose of this experiment was to test the hypothesis that pharmacological activation of the muscarinic cholinergic system during the recovery period after TBI will improve cognitive performance. LU 25-109-T is a partial muscarinic M1 agonist that also acts as an antagonist at presynaptic M2 autoreceptors (thus increasing ACh release). Injured rats were injected subcutaneously daily for 15 days with either 0.0, 3.6, or 15 mumol/kg of LU 25-109-T beginning 24 h after a receiving a moderate (2.1 +/- 0.1 atm) level of central fluid percussion brain injury. Cognitive performance was assessed on days 11-15 postinjury in a Morris water maze (MWM). Injured rats treated with 15 mumol/kg, but not those treated with 3.6 mumol/kg, showed a significant improvement (p < 0.01) in MWM performance as compared with injured vehicle-treated rats. This result supports the hypotheses that a decrease in posttraumatic cholinergic neurotransmission contributes to TBI-induced cognitive deficits and that increasing cholinergic tone during the recovery period following TBI will improve cognitive performance.
创伤性脑损伤（TBI）后的认知障碍与神经元活力的胆碱能标志物减少有关。本实验的目的是检验以下假设：在TBI后的恢复期，毒蕈碱胆碱能系统的药理学激活将改善认知表现。LU 25-109-T是一种部分毒蕈碱M1激动剂，它在突触前M2自身受体处也作为拮抗剂起作用（从而增加乙酰胆碱释放）。在接受中度（2.1±0.1大气压）水平的中心流体冲击性脑损伤24小时后，受伤大鼠每天皮下注射0.0、3.6或15 μmol/kg的LU 25-109-T，持续15天。在损伤后第11 - 15天，在莫里斯水迷宫（MWM）中评估认知表现。与接受溶剂处理的受伤大鼠相比，用15 μmol/kg处理的受伤大鼠，但不是用3.6 μmol/kg处理的大鼠，在MWM表现上有显著改善（p < 0.01）。这一结果支持了以下假设：创伤后胆碱能神经传递的减少导致了TBI诱导的认知缺陷，并且在TBI后的恢复期增加胆碱能张力将改善认知表现。
