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表面活性剂泊洛沙姆188对大鼠颅内出血模型的神经保护作用。

Neuroprotective effect of the surfactant poloxamer 188 in a model of intracranial hemorrhage in rats.

作者信息

Cadichon Sandra B, Le Hoang M, Wright David A, Curry Daniel J, Kang Un, Frim David M

机构信息

Section of Neonatology, The University of Chicago, Chicago, Illinois 60637, USA.

出版信息

J Neurosurg. 2007 Jan;106(1 Suppl):36-40. doi: 10.3171/ped.2007.106.1.36.

Abstract

OBJECT

Neuronal injury remains a leading cause of morbidity in both neonates and adults with injuries induced by intracranial hemorrhage, ischemia-reperfusion, and excitotoxicity. To date, a number of neuroprotective strategies have been evaluated, but they have shown little benefit. Poloxamer 188 (P-188), a membrane-active triblock copolymer, has been studied extensively as a cell-membrane sealant. The authors used an animal model to study the neuroprotectant effects of P-188 administered by intracisternal (IC) injection after experimentally induced intraparenchymal hemorrhage.

METHODS

Sprague-Dawley rats received an IC injection of either P-188 or vehicle (artificial cerebrospinal fluid) 10 minutes after striatal infusion of 50 microl of autologous blood. Animals from both treatment groups were killed either 2 or 7 days later. In a second experiment, after striatal blood infusion and early IC injection of either P-188 or vehicle, animals received daily IC injections of either P- 188 or vehicle for 5 days, and were killed 7 days after induction of the experimental hemorrhage. Striatal tissues were histologically analyzed for neuronal loss, and lesion volumes were determined. Lesion volumes in the animals that received a single dose of P-188 were significantly smaller (mean+/-standard deviation 18.3+/-4.3 mm(3), six rats; p = 0.04) than those in the control group (31.4+/-4.3 mm(3), seven rats) when measured 2 days postinjection; however, no difference in lesion volumes was present 7 days postinjection. Lesion volumes in the animals who received 5 days of daily P-188 injections were significantly smaller (1.50+/-0.58 mm(3), 10 rats; p = 0.04) than those in the corresponding control group (5.04+/-1.85 mm(3), eight rats) when measured at 7 days.

CONCLUSIONS

A single dose of P- 188 protects against early neuronal loss after hemorrhage but has no effect on long-term hemorrhage-induced neuronal loss. However, repeated daily P-188 treatment appears to produce effective long-term neuronal protection.

摘要

目的

在因颅内出血、缺血再灌注和兴奋性毒性导致损伤的新生儿和成人中,神经元损伤仍然是发病的主要原因。迄今为止,已经评估了许多神经保护策略,但收效甚微。泊洛沙姆188(P-188)是一种具有膜活性的三嵌段共聚物,作为一种细胞膜密封剂已被广泛研究。作者使用动物模型研究实验性脑实质内出血后经脑池内(IC)注射给予P-188的神经保护作用。

方法

在向纹状体注入50微升自体血10分钟后,对斯普拉格-道利大鼠进行IC注射P-188或赋形剂(人工脑脊液)。两个治疗组的动物在2天或7天后处死。在第二个实验中,在纹状体注入血液并早期IC注射P-188或赋形剂后,动物每天接受IC注射P-188或赋形剂,持续5天,并在实验性出血诱导后7天处死。对纹状体组织进行组织学分析以评估神经元损失,并测定损伤体积。注射后2天测量时,接受单剂量P-188的动物的损伤体积明显小于对照组(平均值±标准差18.3±4.3立方毫米,6只大鼠;p = 0.04)(31.4±4.3立方毫米,7只大鼠);然而,注射后7天损伤体积没有差异。在7天时测量,接受5天每日P-188注射的动物的损伤体积明显小于相应对照组(1.50±0.58立方毫米,10只大鼠;p = 0.04)(5.04±1.85立方毫米,8只大鼠)。

结论

单剂量P-188可防止出血后早期神经元损失,但对长期出血诱导的神经元损失没有影响。然而,每日重复给予P-188治疗似乎能产生有效的长期神经元保护作用。

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