Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease
Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease
复制标题
DOI：
10.1590/s0100-879x2006005000053
复制
发表时间：
2007-01-01
影响因子：
2.3
通讯作者：
Da Cunha, C.
中科院分区：
文献类型：
--
作者：
Ferro, M.M.;Angelucci, M.E.M.;Da Cunha, C.
在文献中有一个很大的关注神经保护药物治疗帕金森氏病的发展。由于麻醉药物具有超极化特性，它们可能起神经保护剂的作用。在本研究中，我们研究了氯胺酮（85 mg/kg）和甲苯噻嗪（3 mg/kg）的混合物（K/X）对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）或6-羟基多巴胺（6-OHDA）帕金森病大鼠模型的神经保护作用。在硫喷妥钠麻醉下，将MPTP（100 μ g/侧）或6-OHDA（10 μ g/侧）双侧输注到成年雄性Wistar大鼠的黑质延髓部，分别引起酪氨酸羟化酶免疫染色细胞的中度（类似于67%）或重度（类似于91%）损失。另一方面，在手术前5 min用K/X麻醉大鼠时观察到明显的神经保护作用。这种处理导致仅33%的黑质酪氨酸羟化酶免疫染色细胞由于MPTP输注而损失，51%由于6-OHDA输注而损失。K/X的这种神经保护作用也通过用这些神经毒素处理的动物中纹状体多巴胺水平的不太严重的降低而被提出。在Morris水迷宫任务的工作记忆版本中，与对照动物相比，MPTP和6-OHDA损伤的动物在硫喷妥钠麻醉下注入神经毒素的组中花费了近10秒的时间来找到隐藏的平台。在K/X麻醉下输注神经毒素的大鼠中未观察到这种遗忘作用。这些结果表明，具有与K/X相似的药理学特征的药物可能有助于延缓帕金森病的进展。
There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg) and xylazine (3 mg/kg) (K/X) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease. The bilateral infusion of MPTP (100 mu g/side) or 6-OHDA (10 mu g/side) into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (similar to 67%) or severe (similar to 91%) loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33% of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51% due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.