Thrombospondins 1 and 2 are necessary for synaptic plasticity and functional recovery after stroke

被引:226
作者
Liauw, Jason [1 ]
Hoang, Stanley [1 ]
Choi, Michael [1 ]
Eroglu, Cagla [2 ]
Choi, Matthew [1 ]
Sun, Guo-hua [1 ]
Percy, Matthew [1 ]
Wildman-Tobriner, Benjamin [1 ]
Bliss, Tonya [1 ]
Guzman, Raphael G. [1 ]
Barres, Ben A. [2 ]
Steinberg, Gary K. [1 ,3 ]
机构
[1] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA
[3] Stanford Univ, Sch Med, Stanford Stroke Ctr, Stanford, CA 94305 USA
关键词
stroke; thrombospondin; synaptogenesis; functional recovery; structural plasticity; axonal sprouting;
D O I
10.1038/jcbfm.2008.65
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Thrombospondins 1 and 2 (TSP-1/2) belong to a family of extracellular glycoproteins with angiostatic and synaptogenic properties. Although TSP-1/2 have been postulated to drive the resolution of postischemic angiogenesis, their role in synaptic and functional recovery is unknown. We investigated whether TSP-1/2 are necessary for synaptic and motor recovery after stroke. Focal ischemia was induced in 8- to 12-week-old wild-type (WT) and TSP-1/2 knockout (KO) mice by unilateral occlusion of the distal middle cerebral artery and the common carotid artery (CCA). Thrombospondins 1 and 2 increased after stroke, with both TSP-1 and TSP-2 colocalizing mostly to astrocytes. Wild-type and TSP-1/2 KO mice were compared in angiogenesis, synaptic density, axonal sprouting, infarct size, and functional recovery at different time points after stroke. Using the tongue protrusion test of motor function, we observed that TSP-1/2 KO mice exhibited significant deficit in their ability to recover function (P < 0.05) compared with WT mice. No differences were found in infarct size and blood vessel density between the two groups after stroke. However, TSP-1/2 KO mice exhibited significant synaptic density and axonal sprouting deficits. Deficiency of TSP-1/2 leads to impaired recovery after stroke mainly due to the role of these proteins in synapse formation and axonal outgrowth.
引用
收藏
页码:1722 / 1732
页数:11
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