Department of Neurosurgery, Aristotle University of Thessaloniki, Ippokrateio Hospital, Thessaloniki, Greece.
Neuroscience. 2011 Jun 2;183:171-7. doi: 10.1016/j.neuroscience.2011.03.069. Epub 2011 Apr 7.
The aim of this study is to investigate the neuroprotective effects of the anticonvulsant topiramate in a new model of traumatic brain injury in rats. A new model of traumatic brain injury, based on the weight-drop technique, was developed for the purpose of this study. Seventy-five male Wistar rats weighing 320-470 g were studied. All rats were anesthetized, subsequently submitted to a round craniectomy in the left parietal region and a weight of 50 g was used for the production of a cortical contusion. In study I, 44 rats were randomized in three groups to receive either topiramate 40 mg/kg (n=13), topiramate 60 mg/kg (n=14), or water for injection (n=17) i.p. 30 min after the injury and every 12 h thereafter for 3 days. The rats were tested clinically 24 h, 72 h, 10 days and 20 days after the injury. On day 21 the animals were sacrificed and the brains were removed and prepared for histopathological analysis. In study II, 19 rats were randomized to receive either topiramate 60 mg/kg (n=10) or water for injection (n=9) i.p. 30 min after the injury and every 12 h (four doses in total). 48 h after the injury the animals were sacrificed and the brains were rapidly removed and analyzed for water content with the dry-wet weight technique. The animals that received topiramate performed significantly better in neurological tests compared to the animals that received vehicle ten (P<0.05) and 20 (P<0.001) days after the injury. There was no difference between the high and the low dose of the drug. Topiramate had no effect on the anatomic volume of the lesion. The animals that received topiramate had a tendency to present with less cerebral edema formation, but the difference was not statistically significant (P>0.05). These findings suggest that topiramate promotes neurological recovery in rats after traumatic brain injury without affecting the final size of the traumatic lesion and that it might play a role in the reduction of post-traumatic cerebral edema.
本研究旨在探讨抗惊厥药托吡酯在大鼠创伤性脑损伤新模型中的神经保护作用。为了进行本研究，开发了一种基于落体技术的新的创伤性脑损伤模型。75 只雄性 Wistar 大鼠（体重 320-470 克）被纳入研究。所有大鼠均接受麻醉，随后在左侧顶骨区域进行圆形颅骨切除术，并使用 50 克的重量制作皮质挫伤。在研究 I 中，44 只大鼠随机分为三组，分别接受托吡酯 40mg/kg（n=13）、托吡酯 60mg/kg（n=14）或注射用水（n=17）腹腔注射，于损伤后 30 分钟及此后每 12 小时一次，共 3 天。大鼠在损伤后 24 小时、72 小时、10 天和 20 天进行临床测试。第 21 天，处死动物，取出大脑，准备进行组织病理学分析。在研究 II 中，19 只大鼠随机分为两组，分别接受托吡酯 60mg/kg（n=10）或注射用水（n=9）腹腔注射，于损伤后 30 分钟及此后每 12 小时一次，共 4 次。损伤后 48 小时，处死动物，迅速取出大脑，用干湿重法分析含水量。与接受载体的动物相比，接受托吡酯的动物在神经学测试中表现明显更好（P<0.05）和 20（P<0.001）天。药物高剂量和低剂量之间没有差异。托吡酯对病变的解剖体积没有影响。接受托吡酯的动物脑水肿形成倾向减少，但差异无统计学意义（P>0.05）。这些发现表明，托吡酯可促进大鼠创伤性脑损伤后的神经恢复，而不影响创伤性病变的最终大小，并且可能在减少创伤后脑水肿方面发挥作用。
