Reduced evoked release of acetylcholine in the rodent hippocampus following traumatic brain injury
Reduced evoked release of acetylcholine in the rodent hippocampus following traumatic brain injury
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DOI：
10.1016/0091-3057(95)02069-1
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发表时间：
1996-03-01
影响因子：
3.6
通讯作者：
Hayes, RL
中科院分区：
文献类型：
--
作者：
Dixon, CE;Bao, JL;Hayes, RL
通过体内微透析评估创伤性脑损伤对乙酰胆碱释放的慢性影响。在侧向控制皮质冲击 (n = 10) 或假手术 (n = 10) 2 周后，测量麻醉大鼠海马中的乙酰胆碱释放。在微透析之前，对运动和空间记忆进行行为评估。皮质撞击（6 米/秒，2 毫米变形）导致受伤后持续 1 天的横梁平衡缺陷和持续 3 天的横梁行走缺陷。此外，通过莫里斯水迷宫中的游泳潜伏期测量的空间记忆在受伤后 10-14 天内受到损害。行为测试后，立即用氟烷麻醉动物，并将微透析探针置于背海马体中。 160 分钟平衡期后，在腹腔内施用东莨菪碱 (1 mg/kg) 之前和之后测量细胞外乙酰胆碱水平，东莨菪碱通过阻断自身受体引起乙酰胆碱释放。在施用东莨菪碱之前，受伤动物和假手术动物之间的细胞外乙酰胆碱水平没有差异。然而，与假手术对照组相比，受伤动物中东莨菪碱引起的海马乙酰胆碱释放显着减少。在单独的对照组中，单独施用盐水不会改变受伤（n = 5）或假手术（n = 5）动物的海马乙酰胆碱释放。这项研究首次应用体内微透析来评估 TBI 后的慢性神经传递缺陷。本研究表明，足以产生空间记忆缺陷的创伤性脑损伤（TBI）会导致海马内东莨菪碱诱发的乙酰胆碱释放减少。数据进一步表明，介导乙酰胆碱释放的突触前机制可能在 TBI 后胆碱能神经传递缺陷中发挥重要作用。
The chronic effects of traumatic brain injury on acetylcholine release were evaluated by using in vivo microdialysis. Acetylcholine release was measured in the hippocampus of anesthetized rats 2 weeks after lateral controlled cortical impact (n = 10) or sham surgery (n = 10). Prior to microdialysis, behavioral assessments of motor and spatial memory were performed. Cortical impact (6 meter/s, 2 mm deformation) produced beam balance deficits that persisted for 1 day and beam walking deficits that persisted for 3 days after injury. In addition, spatial memory, as measured by swim latencies in a Morris water maze, was compromised between 10-14 days after injury. Immediately following behavioral testing, the animals were anesthetized with halothane, and a microdialysis probe was placed into the dorsal hippocampus. After a 160 min equilibration period, extracellular levels of acetylcholine were measured prior to and after an intraperitoneal administration of scopolamine (1 mg/kg), which evokes acetylcholine release by blocking autoreceptors. Prior to scopolamine administration, there were no differences in extracellular levels of acetylcholine between injured and sham animals. However, there was a significant reduction of hippocampal acetylcholine release evoked by scopolamine in injured animals as compared to sham controls. In separate control groups, saline administration alone did not change hippocampal acetylcholine release in injured(n = 5) or sham (n = 5) animals. This study represents the first application of in vivo microdialysis to evaluate chronic neurotransmission deficits following TBI. The present study demonstrates that a magnitude of traumatic brain injury (TBI) sufficient to produce spatial memory deficits can result in a reduction in scopolamine-evoked release of acetylcholine within the hippocampus. The data further suggest that presynaptic mechanisms mediating release of acetylcholine could play a significant role in cholinergic neurotransmission deficits following TBI.