Protection after stroke: cellular effectors of neurovascular unit integrity.
Protection after stroke: cellular effectors of neurovascular unit integrity.
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DOI：
10.3389/fncel.2014.00231
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发表时间：
2014
影响因子：
5.3
通讯作者：
Cardona-Gomez GP
中科院分区：
文献类型：
--
作者：
Posada-Duque RA;Barreto GE;Cardona-Gomez GP
神经性疾病在世界范围内很普遍。脑血管疾病(CVD)占所有神经系统疾病的55%，是导致永久性残疾、认知和运动障碍以及痴呆的主要原因。卒中影响血脑屏障的功能和结构、脑血流调节的丧失、氧化应激、炎症和神经联系的丧失。目前，除了急性治疗窗口外，尚无金标准治疗方法可用于改善中风患者的预后。一些有希望的候选靶点已被确定为改善卒中后长期康复的靶点，如Rho GTP酶、细胞黏附蛋白、激酶和磷酸酶。我们实验室以前的研究表明，Rho GTP酶(RAC和RhoA)参与了组织损伤和存活，因为这些蛋白对神经元、星形胶质细胞和内皮细胞的形态和运动是必不可少的，因此在细胞生存和死亡之间的平衡中发挥着关键作用。用RhoA/ROCK的药物抑制剂治疗可以阻止神经退行性变级联反应的激活。此外，RAC和突触黏附蛋白(p120连环蛋白和N-连环蛋白)通过支持神经血管单位和细胞骨架重塑活动来维持脑实质的完整性，在脑梗塞的保护和恢复中发挥关键作用。有趣的是，神经保护剂，如阿托伐他汀，在脑缺血后和谷氨酸诱导的兴奋性毒性模型中，CDK5的沉默可能作用于相同的细胞效应器，以恢复神经血管单位的完整性。因此，今后的研究工作必须针对脑缺血后神经血管单位的各个效应器的结构和功能作用，以及神经和非神经细胞之间的相互作用，解决如何在短、中、长期促进或防止内稳态的恢复或丧失。
Neurological disorders are prevalent worldwide. Cerebrovascular diseases (CVDs), which account for 55% of all neurological diseases, are the leading cause of permanent disability, cognitive and motor disorders and dementia. Stroke affects the function and structure of blood-brain barrier, the loss of cerebral blood flow regulation, oxidative stress, inflammation and the loss of neural connections. Currently, no gold standard treatments are available outside the acute therapeutic window to improve outcome in stroke patients. Some promising candidate targets have been identified for the improvement of long-term recovery after stroke, such as Rho GTPases, cell adhesion proteins, kinases, and phosphatases. Previous studies by our lab indicated that Rho GTPases (Rac and RhoA) are involved in both tissue damage and survival, as these proteins are essential for the morphology and movement of neurons, astrocytes and endothelial cells, thus playing a critical role in the balance between cell survival and death. Treatment with a pharmacological inhibitor of RhoA/ROCK blocks the activation of the neurodegeneration cascade. In addition, Rac and synaptic adhesion proteins (p120 catenin and N-catenin) play critical roles in protection against cerebral infarction and in recovery by supporting the neurovascular unit and cytoskeletal remodeling activity to maintain the integrity of the brain parenchyma. Interestingly, neuroprotective agents, such as atorvastatin, and CDK5 silencing after cerebral ischemia and in a glutamate-induced excitotoxicity model may act on the same cellular effectors to recover neurovascular unit integrity. Therefore, future efforts must focus on individually targeting the structural and functional roles of each effector of neurovascular unit and the interactions in neural and non-neural cells in the post-ischemic brain and address how to promote the recovery or prevent the loss of homeostasis in the short, medium and long term.
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DOI：
10.1111/j.1538-7836.2008.03087.x
发表时间：
2008-09
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Aghajanian A;Wittchen ES;Allingham MJ;Garrett TA;Burridge K
通讯作者：
Burridge K
影响因子：
8.3
作者：
Alkayed, NJ;Birks, EK;Harder, DR
通讯作者：
Harder, DR
影响因子：
5.3
作者：
Alexander, K;Yang, HS;Hinds, PW
通讯作者：
Hinds, PW
影响因子：
4.7
作者：
Andersson, AK;Rönnbäck, L;Hansson, E
通讯作者：
Hansson, E
影响因子：
3.7
作者：
Barreto GE;Sun X;Xu L;Giffard RG
通讯作者：
Giffard RG