Harnessing hypoxic adaptation to prevent, treat, and repair stroke.
Harnessing hypoxic adaptation to prevent, treat, and repair stroke.
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DOI：
10.1007/s00109-007-0283-1
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发表时间：
2007-12
影响因子：
4.7
通讯作者：
LaManna, Joseph
中科院分区：
文献类型：
--
作者：
Ratan, Rajiv R.;Siddiq, Ambreena;Smirnova, Natalya;Karpisheva, Ksenia;Haskew-Layton, Renee;McConoughey, Stephen;Langley, Brett;Estevez, Alvaro;Huerta, Patricio T.;Volpe, Bruce;Roy, Sashwati;Sen, Chandan K.;Gazaryan, Irina;Cho, Sunghee;Fink, Matthew;LaManna, Joseph
大脑需要氧气和葡萄糖来履行其作为身体功能的主要调节器的角色，这些功能包括膀胱控制和创造性思维。在中风中，由于缺氧和低血糖，神经系统中的化学和电传递迅速中断。尽管其结构高度进化，但人类大脑似乎利用遗传学保守的稳态策略来对抗缺氧和缺血。具体来说，几个汇聚的调查线已经证明，转录因子缺氧诱导因子-1（HIF 1 - 1）介导激活的一个大的基因盒参与适应缺氧在中风后存活的神经元。因此，在其传感器之一（例如，HIF脯氨酰4羟化酶的抑制）导致脑组织的深度保留和增强的功能恢复。在这篇综述中，我们讨论了潜在的机制，可以subserve保护和恢复作用的增强缺氧适应的大脑。该策略似乎涉及HIF依赖性和HIF非依赖性途径以及70多种转录和转录后激活的基因和蛋白质，这些基因和蛋白质可以在细胞，局部和系统水平上起作用以补偿氧不足。这种自我平衡计划的广度和深度为目前对中风治疗的悲观情绪提供了一种有希望的替代方案。
The brain demands oxygen and glucose to fulfill its roles as the master regulator of body functions as diverse as bladder control and creative thinking. Chemical and electrical transmission in the nervous system is rapidly disrupted in stroke as a result of hypoxia and hypoglycemia. Despite being highly evolved in its architecture, the human brain appears to utilize phylogenetically conserved homeostatic strategies to combat hypoxia and ischemia. Specifically, several converging lines of inquiry have demonstrated that the transcription factor hypoxia-inducible factor-1 (HIF1-1) mediates the activation of a large cassette of genes involved in adaptation to hypoxia in surviving neurons after stroke. Accordingly, pharmacological or molecular approaches that engage hypoxic adaptation at the point of one of its sensors (e.g., inhibition of HIF prolyl 4 hydroxylases) leads to profound sparing of brain tissue and enhanced recovery of function. In this review, we discuss the potential mechanisms that could subserve protective and restorative effects of augmenting hypoxic adaptation in the brain. The strategy appears to involve HIF-dependent and HIF-independent pathways and more than 70 genes and proteins activated transcriptionally and post-transcriptionally that can act at cellular, local, and system levels to compensate for oxygen insufficiency. The breadth and depth of this homeostatic program offers a hopeful alternative to the current pessimism towards stroke therapeutics.
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影响因子：
50.3
作者：
Lee, S;Nakamura, E;Schlisio, S
通讯作者：
Schlisio, S
影响因子：
6.3
作者：
Cho, S;Park, EM;Iadecola, C
通讯作者：
Iadecola, C
影响因子：
5.3
作者：
Chavez, Juan C.;Baranova, Oxana;Pichiule, Paola
通讯作者：
Pichiule, Paola
影响因子：
5.5
作者：
Ito, Norimasa;DeMarco, Richard A.;Lotze, Michael T.
通讯作者：
Lotze, Michael T.
DOI：
10.1073/pnas.88.14.6368
发表时间：
1991-07-01
影响因子：
11.1
作者：
DAWSON, VL;DAWSON, TM;SNYDER, SH
通讯作者：
SNYDER, SH