Suppr超能文献

肌球蛋白轻链激酶抑制减少创伤性脑损伤后脑水肿的形成。

Inhibition of myosin light chain kinase reduces brain edema formation after traumatic brain injury.

机构信息

Department of Anesthesiology, Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

出版信息

J Neurochem. 2010 Feb;112(4):1015-25. doi: 10.1111/j.1471-4159.2009.06514.x. Epub 2009 Nov 27.

Abstract

The role of the endothelial contractile apparatus in the process of brain edema formation after brain trauma is not characterized. Phosphorylation of myosin light chains by myosin light chain kinases (MLCK) activates endothelial contractile elements and results in a rearrangement of the cytoskeleton. This may enhance post-traumatic blood-brain barrier dysfunction. In order to investigate the role of the MLCK on brain edema formation and blood-brain barrier permeability after brain injury, mice were anesthetized and subjected to a controlled cortical impact (CCI). MLCK expression is significantly up-regulated after CCI with a maximum 12 h post-injury. Specific inhibition of MLCK by ML-7 resulted in a reduction of phosphorylation of myosin light chains and improved blood-brain-barrier integrity. Accordingly, ML-7 attenuated post-traumatic brain edema formation and intracranial hypertension 24 h after CCI. Prevention of brain edema formation did not translate into improved neurological outcome or reduced brain lesion. In conclusion, the results confirm that the endothelial contractile apparatus is activated by CCI and opens the endothelial barrier leading to vasogenic brain edema formation. Lack of neurological and histological improvement suggests that specific targeting of vasogenic brain edema at the endothelial level is not sufficient to limit secondary brain damage and has, therefore, to be combined with other potential neuroprotective strategies.

摘要

内皮细胞收缩装置在创伤性脑损伤后脑水肿形成过程中的作用尚不清楚。肌球蛋白轻链激酶(MLCK)使肌球蛋白轻链磷酸化,激活内皮收缩元件,导致细胞骨架重排。这可能会增强创伤后血脑屏障功能障碍。为了研究 MLCK 在创伤性脑损伤后脑水肿形成和血脑屏障通透性中的作用,对小鼠进行麻醉并进行皮质控制冲击(CCI)。CCI 后 MLCK 的表达明显上调,损伤后 12 小时达到最大值。ML-7 特异性抑制 MLCK 导致肌球蛋白轻链的磷酸化减少,并改善血脑屏障的完整性。因此,ML-7 可减轻 CCI 后 24 小时的创伤性脑水肿形成和颅内压升高。预防脑水肿形成并没有转化为改善神经功能或减少脑损伤。总之,这些结果证实,内皮细胞收缩装置在 CCI 作用下被激活,并打开内皮屏障,导致血管源性脑水肿形成。缺乏神经和组织学改善表明,内皮水平上针对血管源性脑水肿的特异性靶向治疗不足以限制继发性脑损伤,因此必须与其他潜在的神经保护策略相结合。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验