Doccol线栓;大鼠MCAO线栓;MCAO栓线;脑缺血线栓

Doccol线拴是国际脑缺血研究中常用线拴，是Nature，Stroke，J Neurosci 等杂志报道最多的线拴。根据谷歌学术的搜索结果，截止至目前，已经有数千篇研究脑缺血的文献引用了Doccol线栓。仅2024年1月至12月就有347篇，文献目录见我们的网站。美国的Doccol线拴是脑缺血MCAO模型稳定的保证，可将脑梗塞体积标准差减少至5%，并避免蛛网膜下腔出血，不需要激光多普勒检测血流也能获得极为稳定的结果。同时，每只鼠MCAO的线栓成本最低仅为30-50元（可重复使用型号，视重复使用次数决定）。我们是Doccol线栓中国总代理，我们推荐使用下表的型号，推荐型号备有现货。访问我们的网站，可观摩大小鼠MCAO模型视频。

种属	体重（g）	推荐型号（可重复用）	线号	外径（mm）	包被长度（mm）
小鼠	15-20	701934PK5Re	7-0	0.19	3-4
		701956PK5Re	7-0	0.19	5-6
	20-25	602156PK5Re	6-0	0.21	5-6
		602256PK5Re	6-0	0.22	5-6
	25-30	602256PK5Re	6-0	0.22	5-6
		602356PK5Re	6-0	0.23	5-6
	30-35	602356PK5Re	6-0	0.23	5-6
大鼠	<200	503356PK5Re	5-0	0.33	5-6
	200-250	403556PK5Re	4-0	0.35	5-6
	250-280	403756PK5Re	4-0	0.37	5-6
	280-330	403956PK5Re	4-0	0.39	5-6
	330-400	404156PK5Re	4-0	0.41	5-6
	>400	404356PK5Re	4-0	0.43	5-6

 

注：（1）型号的命名根据线号、外径、硅胶包被长度、一个包装中的线拴数量、是否可重复使用确定。如“701956PK5Re”为7号线，0.19mm外径，硅胶包被长度5-6mm，PK5一个包装中的数量是5根，Re可重复使用。（2）在美国，绝大多数的实验者都选用上表推荐的可重复使用型号，即所谓“starter kits”。Doccol线栓所有型号列表及选择原则见我司网站。（3）一次性线栓（名称中不带Re字样）每管10根，价格与可重复型号相同。（4）Re型号重复使用的次数，每位实验者差别很大，2-10次不等。

Doccol MCAO线拴可以将脑梗塞体积标准差减少至5%

成功的MCAO模型的脑血流在插入线拴时会有断崖式下降；在拔出线拴后，激光多普勒检测的血流会很快恢复（图A）。采用硬质尼龙鱼线线拴，极易戳破血管，造成蛛网膜下腔出血（Subarachnoid hemorrhage，图B）。手术过程中血管如果被线拴戳破，脑血流不会有断崖式下降，而是缓慢下降；在拔出线拴后，脑血流也不会恢复。造成脑梗塞体积变异的原因还有，不完全的梗塞血管或线拴移位造成的血流下降程度不均一及提前灌注。因此，线栓的质地是MCAO模型稳定的关键。



对于MCAO模型来说，主要有两种线拴，无包被的火焰熔烫圆头线拴及硅胶包被线拴。研究表明(Tsuchiya et al. 2003)，无包被的圆头线拴在MCAO实验过程中可能导致高达40%的蛛网膜下腔出血，而其标准差可能比平均值的50%还要大。另一项技术文章表明(Shimamura et al. 2006a)，硅胶包被线拴要远好于无包被的圆头线拴，其结果更为稳定，即使对于没有经验的实验者来说也是如此。而多聚赖氨酸包被的线拴只能增加死亡率，不能减少梗赛体积的变异程度(Huang et al. 1998)。

Doccol MCAO线拴全部为硅胶包被，圆润、柔软、包被均匀，即使在没有激光多普勒实时检测的情况，也不会将血管戳破。使用自制的硅胶包被的线拴，大鼠(Schmid-Elsaesser et al. 1998)及小鼠(Shah et al. 2006)的脑梗塞体积的标准差均在30%左右。而使用Doccol MCAO线拴可以得到更好的结果。对于大鼠MCAO模型来说，使用Doccol MCAO线拴得到的结果的标准差可达10%-20% （Ruscher et al.2012；Ishizaka et al.2013；Sakata et al.2012；Candelario-Jalil et al. 2008；Khan et al. 2006；Liu et al. 2006；Shimamura et al. 2006b；Solaroglu et al. 2006；Tsubokawa et al. 2007；Tsubokawa et al. 2006a；Tsubokawa et al. 2006b)。对于小鼠来说，使用Doccol MCAO线拴得到的结果的标准差可达5%-10%(Chen et al.2014; Bae et al.2013; Jin et al.2011; Gu et al.2012; Kleinschnitz et al. 2007; Maysami et al. 2008; Pignataro et al. 2007b; Pignataro et al. 2007c)。

References

1. Bae ON, Serfozo K, Baek SH, et al. (2013) Safety and efficacy evaluation of carnosine, an endogenous neuroprotective agent for ischemic stroke. Stroke 44(1):205-12.

2. Candelario-Jalil E, Munoz E, Fiebich BL. (2008) Detrimental effects of tropisetron on permanent ischemic stroke in the rat. BMC Neurosci 9:19

3. Chen HZ, Guo S, Li ZZ, et al. (2014) A critical role for interferon regulatory factor 9 in cerebral ischemic stroke.J Neurosci.34(36):11897-912.

4. Huang J, Kim LJ, Poisik A, Pinsky DJ, Connolly ES, Jr. (1998) Does poly-L-lysine coating of the middle cerebral artery occlusion suture improve infarct consistency in a murine model? J Stroke Cerebrovasc Dis 7:296-301

5. Gu L, Xiong X, Zhang H, et al. (2012) Distinctive Effects of T Cell Subsets in Neuronal Injury Induced by Cocultured Splenocytes In Vitro and by In Vivo Stroke in Mice. Stroke 43:1941-1946.

6. Ishizaka S, Horie N, Satoh K, et al. (2013) Intra-arterial Cell Transplantation Provides Timing-Dependent Cell Distribution and Functional Recovery After Stroke. Stroke 44:720-726.

7. Jin R, Song Z, Yu S, et al. (2011) Phosphatidylinositol-3-kinase gamma plays a central role in blood-brain barrier dysfunction in acute experimental stroke.Stroke 42(7):2033-44.

8. Khan M, Jatana M, Elango C, Paintlia AS, Singh AK, Singh I. (2006) Cerebrovascular protection by various nitric oxide donors in rats after experimental stroke. Nitric Oxide 15:114-124

9. Kleinschnitz C, Pozgajova M, Pham M, Bendszus M, Nieswandt B, Stoll G. (2007) Targeting platelets in acute experimental stroke: impact of glycoprotein Ib, VI, and IIb/IIIa blockade on infarct size, functional outcome, and intracranial bleeding. Circulation 115:2323-2330

10. Koizumi J, Yoshida Y, Nakazawa T, Ooneda G. (1986) Experimental studies of ischemic brain edema, I: a new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jpn J Stroke 8:1-8

11. Liu S, Liu W, Ding W, Miyake M, Rosenberg GA, Liu KJ. (2006) Electron paramagnetic resonance-guided normobaric hyperoxia treatment protects the brain by maintaining penumbral oxygenation in a rat model of transient focal cerebral ischemia. J Cereb Blood Flow Metab 26:1274-1284

12. Longa EZ, Weinstein PR, Carlson S, Cummins R. (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84-91

13. Maysami S, Lan JQ, Minami M, Simon RP. (2008) Proliferating progenitor cells: a required cellular element for induction of ischemic tolerance in the brain. J Cereb Blood Flow Metab 28:1104-1113

14. Pignataro G, Simon RP, Boison D. (2007a) Transgenic overexpression of adenosine kinase aggravates cell death in ischemia. J Cereb Blood Flow Metab 27:1-5

15. Pignataro G, Simon RP, Xiong ZG. (2007b) Prolonged activation of ASIC1a and the time window for neuroprotection in cerebral ischaemia. Brain 130:151-158

16. Pignataro G, Studer FE, Wilz A, Simon RP, Boison D. (2007c) Neuroprotection in ischemic mouse brain induced by stem cell-derived brain implants. J Cereb Blood Flow Metab 27:919-927

17. Ruscher K, Kuric E, Wieloch T, et al. (2012) Levodopa Treatment Improves Functional Recovery After Experimental Stroke. Stroke 43:507-513.

18. Sakata H, et al. (2012) Minocycline-Preconditioned Neural Stem Cells Enhance Neuroprotection after Ischemic Stroke in Rats. J Neurosci. 32(10):3462–3473.

19 Schmid-Elsaesser R, Zausinger S, Hungerhuber E, Baethmann A, Reulen HJ. (1998) A critical reevaluation of the intraluminal thread model of focal cerebral ischemia: evidence of inadvertent premature reperfusion and subarachnoid hemorrhage in rats by laser-Doppler flowmetry. Stroke 29:2162-2170

20. Shah ZA, Namiranian K, Klaus J, Kibler K, Dore S. (2006) Use of an optimized transient occlusion of the middle cerebral artery protocol for the mouse stroke model. J Stroke Cerebrovasc Dis 15:133-138

21. Shimamura N, Matchett G, Tsubokawa T, Ohkuma H, Zhang J. (2006a) Comparison of silicon-coated nylon suture to plain nylon suture in the rat middle cerebral artery occlusion model. J Neurosci Methods 156:161-165

22. Shimamura N, Matchett G, Yatsushige H, Calvert JW, Ohkuma H, Zhang J. (2006b) Inhibition of integrin alphavbeta3 ameliorates focal cerebral ischemic damage in the rat middle cerebral artery occlusion model. Stroke 37:1902-1909

23. Solaroglu I, Tsubokawa T, Cahill J, Zhang JH. (2006) Anti-apoptotic effect of granulocyte-colony stimulating factor after focal cerebral ischemia in the rat. Neuroscience 143:965-974

24. Tsubokawa T, Jadhav V, Solaroglu I, Shiokawa Y, Konishi Y, Zhang JH. (2007) Lecithinized superoxide dismutase improves outcomes and attenuates focal cerebral ischemic injury via antiapoptotic mechanisms in rats. Stroke 38:1057-1062

25. Tsubokawa T, Solaroglu I, Yatsushige H, Cahill J, Yata K, Zhang JH. (2006a) Cathepsin and calpain inhibitor E64d attenuates matrix metalloproteinase-9 activity after focal cerebral ischemia in rats. Stroke 37:1888-1894

26. Tsubokawa T, Yamaguchi-Okada M, Calvert JW, Solaroglu I, Shimamura N, Yata K, Zhang JH. (2006b) Neurovascular and neuronal protection by E64d after focal cerebral ischemia in rats. J Neurosci Res 84:832-840

27. Tsuchiya D, Hong S, Kayama T, Panter SS, Weinstein PR. (2003) Effect of suture size and carotid clip application upon blood flow and infarct volume after permanent and temporary middle cerebral artery occlusion in mice. Brain Res 970:131-139