Mouse intracerebral hemorrhage models produce different degrees of initial and delayed damage, axonal sprouting, and recovery

Mouse intracerebral hemorrhage models produce different degrees of initial and delayed damage, axonal sprouting, and recovery
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DOI:
10.1038/jcbfm.2014.107
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发表时间:
2014-09-01
影响因子:
6.3
通讯作者:
Carmichael, S. Thomas
Carmichael, S. Thomas
中科院分区:
医学1区
文献类型:
--
作者:
Barratt, Harriet E.;Lanman, Tyler A.;Carmichael, S. Thomas

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脑出血(ICH)后延迟性损伤和恢复的机制仍不清楚。通常使用两种啮齿动物ICH模型:注射胶原酶(cICH)和注射自体血(bICH)。在小鼠中,我们比较了这两种模型对初始和延迟组织损伤、运动系统连接和行为恢复的影响。模型之间的病变尺寸没有差异。注射自体血引起更大的占位效应和早期死亡。然而,cICH会产生更严重的水肿、炎症和细胞死亡。注射胶原酶会导致皮质连接的更大损失和纹状体的继发性收缩。脑出血发生在纹状体的运动系统连接内。前肢运动区的投射映射显示仅在cICH中运动皮层投射中出现显著的萌芽。两种ICH模型均产生前肢运动控制缺陷。cICH中5周和bICH中9周时发生行为恢复。总之,cICH和bICH在初始和迟发性卒中病理生理学的几乎每个方面都不同,cICH比bICH产生更大的初始和继发性组织损伤以及更大的运动系统轴突发芽。两种模型中均发生运动恢复,表明cICH中运动系统轴突发芽与恢复无因果关系。
The mechanisms of delayed damage and recovery after intracerebral hemorrhage (ICH) remain poorly defined. Two rodent models of ICH are commonly used: injection of the enzyme collagenase (cICH) and injection of autologous blood (bICH). In mice, we compared the effects of these two models on initial and delayed tissue damage, motor system connections, and behavioral recovery. There is no difference in lesion size between models. Injection of autologous blood causes greater mass effect and early mortality. However, cICH produces greater edema, inflammation, and cell death. Injection of the enzyme collagenase causes greater loss of cortical connections and secondary shrinkage of the striatum. Intracerebral hemorrhage occurs within the motor system connections of the striatum. Mapping of the projections of the forelimb motor area shows a significant sprouting in motor cortex projections only in cICH. Both models of ICH produce deficits in forelimb motor control. Behavioral recovery occurs by 5 weeks in cICH and 9 weeks in bICH. In summary, cICH and bICH differ in almost every facet of initial and delayed stroke pathophysiology, with cICH producing greater initial and secondary tissue damage and greater motor system axonal sprouting than bICH. Motor recovery occurs in both models, suggesting that motor system axonal sprouting in cICH is not causally associated with recovery.