头孢曲松可降低 6-羟多巴胺帕金森病模型中左旋多巴诱导的运动障碍严重程度。
Ceftriaxone reduces L-dopa-induced dyskinesia severity in 6-hydroxydopamine parkinson's disease model.
机构信息
Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, New York, USA.
出版信息
Mov Disord. 2017 Nov;32(11):1547-1556. doi: 10.1002/mds.27077. Epub 2017 Jun 20.
BACKGROUND
Increased extracellular glutamate may contribute to l-dopa induced dyskinesia, a debilitating side effect faced by Parkinson's disease patients 5 to 10 years after l-dopa treatment. Therapeutic strategies targeting postsynaptic glutamate receptors to mitigate dyskinesia may have limited success because of significant side effects. Increasing glutamate uptake may be another approach to attenuate excess glutamatergic neurotransmission to mitigate dyskinesia severity or prolong the time prior to onset. Initiation of a ceftriaxone regimen at the time of nigrostriatal lesion can attenuate tyrosine hydroxylase loss in conjunction with increased glutamate uptake and glutamate transporter GLT-1 expression in a rat 6-hydroxydopamine model. In this article, we examined if a ceftriaxone regimen initiated 1 week after nigrostriatal lesion, but prior to l-dopa, could reduce l-dopa-induced dyskinesia in an established dyskinesia model.
METHODS
Ceftriaxone (200 mg/kg, intraperitoneal, once daily, 7 consecutive days) was initiated 7 days post-6-hydroxydopamine lesion (days 7-13) and continued every other week (days 21-27, 35-39) until the end of the study (day 39 postlesion, 20 days of l-dopa).
RESULTS
Ceftriaxone significantly reduced abnormal involuntary movements at 5 time points examined during chronic l-dopa treatment. Partial recovery of motor impairment from nigrostriatal lesion by l-dopa was unaffected by ceftriaxone. The ceftriaxone-treated l-dopa group had significantly increased striatal GLT-1 expression and glutamate uptake. Striatal tyrosine hydroxylase loss in this group was not significantly different when compared with the l-dopa alone group.
CONCLUSIONS
Initiation of ceftriaxone after nigrostriatal lesion, but prior to and during l-dopa, may reduce dyskinesia severity without affecting l-dopa efficacy or the reduction of striatal tyrosine hydroxylase loss. © 2017 International Parkinson and Movement Disorder Society.
背景
细胞外谷氨酸的增加可能导致左旋多巴诱导的运动障碍，这是帕金森病患者在接受左旋多巴治疗 5 至 10 年后面临的一种衰弱的副作用。针对突触后谷氨酸受体的治疗策略可能无法成功缓解运动障碍，因为其会产生显著的副作用。增加谷氨酸摄取可能是另一种减轻谷氨酸能神经传递过度的方法，从而减轻运动障碍的严重程度或延长发病前的时间。在黑质纹状体损伤时开始头孢曲松治疗，可以减轻酪氨酸羟化酶的损失，同时增加谷氨酸摄取和谷氨酸转运体 GLT-1 在大鼠 6-羟多巴胺模型中的表达。在本文中，我们研究了在黑质纹状体损伤后 1 周开始头孢曲松治疗，但在左旋多巴之前，是否可以在已建立的运动障碍模型中减少左旋多巴诱导的运动障碍。
方法
头孢曲松（200mg/kg，腹腔内，每天 1 次，连续 7 天）在 6-羟多巴胺损伤后 7 天（第 7-13 天）开始，并每隔一周继续（第 21-27 天，第 35-39 天），直到研究结束（损伤后第 39 天，左旋多巴 20 天）。
结果
头孢曲松显著减少了慢性左旋多巴治疗期间检查的 5 个时间点的异常不自主运动。左旋多巴对黑质纹状体损伤引起的运动障碍的部分恢复不受头孢曲松的影响。与单独使用左旋多巴组相比，头孢曲松治疗的左旋多巴组纹状体 GLT-1 表达和谷氨酸摄取显著增加。该组纹状体酪氨酸羟化酶的损失与单独使用左旋多巴组无显著差异。
结论
在黑质纹状体损伤后、左旋多巴治疗前和治疗期间开始使用头孢曲松，可能会减轻运动障碍的严重程度，而不会影响左旋多巴的疗效或减少纹状体酪氨酸羟化酶的损失。© 2017 国际帕金森病和运动障碍学会。
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