Delayed riluzole treatment is able to rescue injured rat spinal motoneurons
Delayed riluzole treatment is able to rescue injured rat spinal motoneurons
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DOI：
10.1016/j.neuroscience.2006.09.046
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发表时间：
2007-01
期刊：
影响因子：
3.3
通讯作者：
A. Nógrádi;A. Szabo;S. Pintér;G. Vrbóva
中科院分区：
文献类型：
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作者：
A. Nógrádi;A. Szabo;S. Pintér;G. Vrbóva
研究了延迟的2-氨基-6-三氟甲氧基-苯并噻唑（利鲁唑）治疗对损伤的运动神经元的影响。将成年大鼠L4前根撕脱并重新植入脊髓。手术后立即或延迟5、10、14或16天，用利鲁唑处理动物（每组n=5），而另外4只动物保持未处理。术后3个月，将荧光染料Fast Blue应用于L4脊神经切断的腹侧支的近端，以逆行标记再支配神经元。3天后取脊髓行逆行标记细胞计数，并行胆碱乙酰转移酶免疫组化染色，观察脊髓内胆碱能细胞。在未处理的动物中，20.4±1.6（±S.E.M.）逆行标记的神经元，而在前根撕脱后立即或5和10天用利鲁唑处理的动物中，标记的运动神经元的数量范围在763±36和815±50（S.E.M.）之间。在损伤后14天和16天开始的阿曲唑治疗导致显著较低数量的再神经支配运动神经元（67±4和52±3 S.E.M.，分别）。因此，利鲁唑不仅在损伤后立即开始治疗时，而且在利鲁唑治疗延迟长达10天的情况下，都显著增强了受损运动神经元的存活和神经再支配能力。这些结果表明，运动神经元注定要死亡后，前根撕脱后，编程生存一段时间后，损伤和利鲁唑是能够拯救他们在这段时间。
The effect of delayed 2-amino-6-trifluoromethoxy-benzothiazole (riluzole) treatment on injured motoneurons was studied. The L4 ventral root of adult rats was avulsed and reimplanted into the spinal cord. Immediately after the operation or with a delay of 5, 10, 14 or 16 days animals were treated with riluzole (n=5 in each group) while another four animals remained untreated. Three months after the operation the fluorescent dye Fast Blue was applied to the proximal end of the cut ventral ramus of the L4 spinal nerve to retrogradely label reinnervating neurons. Three days later the spinal cords were processed for counting the retrogradely labeled cells and choline acetyltransferase immunohistochemistry was performed to reveal the cholinergic cells in the spinal cords. In untreated animals there were 20.4±1.6 (±S.E.M.) retrogradely labeled neurons while in animals treated with riluzole immediately or 5 and 10 days after ventral root avulsion the number of labeled motoneurons ranged between 763±36 and 815±50 (S.E.M.). Riluzole treatment starting at 14 and 16 days after injury resulted in significantly lower number of reinnervating motoneurons (67±4 and 52±3 S.E.M., respectively). Thus, riluzole dramatically enhanced the survival and reinnervating capacity of injured motoneurons not only when treatment started immediately after injury but also in cases when riluzole treatment was delayed for up to 10 days. These results suggest that motoneurons destined to die after ventral root avulsion are programmed to survive for some time after injury and riluzole is able to rescue them during this period of time.