Department of Neurology, University of Münster, Münster, Germany.
Stroke. 2012 Jul;43(7):1931-40. doi: 10.1161/STROKEAHA.112.654806. Epub 2012 May 10.
The neuroprotective potential of citicoline in acute ischemic stroke has been shown in many experimental studies and, although the exact mechanisms are still unknown, a clinical Phase III trial is currently underway. Our present study was designed to check whether citicoline also enhances neuroregeneration after experimental stroke.
Forty Wistar rats were subjected to photothrombotic stroke and treated either with daily injections of citicoline (100 mg/kg) or vehicle for 10 consecutive days starting 24 hours after ischemia induction. Sensorimotor tests were performed after an adequate training period at Days 1, 10, 21, and 28 after stroke. Then brains were removed and analyzed for infarct size, glial scar formation, neurogenesis, and ligand binding densities of excitatory and inhibitory neurotransmitter receptors.
Animals treated with citicoline showed a significantly better neurological outcome at Days 10, 21, and 28 after ischemia, which could not be attributed to differences in infarct volumes or glial scar formation. However, neurogenesis in the dentate gyrus, subventricular zone, and peri-infarct area was significantly increased by citicoline. Furthermore, enhanced neurological outcome after citicoline treatment was associated with a shift toward excitation in the perilesional cortex.
Our present data demonstrate that, apart from the well-known neuroprotective effects in acute ischemic stroke, citicoline also possesses a substantial neuroregenerative potential. Thanks to its multimodal effects, easy applicability, and history as a well-tolerated drug, promising possibilities of neurological treatment including chronic stroke open up.
胞磷胆碱在急性缺血性卒中中的神经保护作用已在许多实验研究中得到证实，尽管确切机制尚不清楚，但目前正在进行一项临床 III 期试验。我们的本研究旨在检查胞磷胆碱是否也能增强实验性卒中后的神经再生。
40 只 Wistar 大鼠接受光血栓性卒中，并在缺血诱导后 24 小时开始连续 10 天每天接受胞磷胆碱（100mg/kg）或载体治疗。在卒中后第 1、10、21 和 28 天进行了充分的训练期后，进行了感觉运动测试。然后取出大脑，分析梗死体积、神经胶质瘢痕形成、神经发生以及兴奋性和抑制性神经递质受体的配体结合密度。
接受胞磷胆碱治疗的动物在缺血后第 10、21 和 28 天的神经功能结果明显更好，这不能归因于梗死体积或神经胶质瘢痕形成的差异。然而，齿状回、室下区和梗死周围区的神经发生明显增加。此外，胞磷胆碱治疗后的神经功能改善与皮质下皮层向兴奋的转变有关。
我们目前的数据表明，除了在急性缺血性卒中中具有众所周知的神经保护作用外，胞磷胆碱还具有显著的神经再生潜力。由于其多模式作用、易于应用以及作为一种耐受性良好的药物的历史，为包括慢性中风在内的神经治疗开辟了有希望的可能性。
