Vascular endothelial growth factor induces contralesional corticobulbar plasticity and functional neurological recovery in the ischemic brain

被引:68
作者
Reitmeir, Raluca [1 ]
Kilic, Ertugrul [2 ]
Reinboth, Barbara S. [1 ]
Guo, Zeyun [1 ]
ElAli, Ayman [1 ]
Zechariah, Anil [1 ]
Kilic, Ulkan [3 ]
Hermann, Dirk M. [1 ]
机构
[1] Univ Hosp Essen, Dept Neurol, D-45122 Essen, Germany
[2] Yeditepe Univ Istanbul, Dept Physiol, Istanbul, Turkey
[3] Vakif Univ Istanbul, Dept Med Biol, Istanbul, Turkey
关键词
Anterograde tract tracing; Axonal sprouting; Ischemic stroke; Guidance cues; Neurovascular remodeling; FOCAL CEREBRAL-ISCHEMIA; POSTISCHEMIC NEUROPROTECTION; EXPERIMENTAL STROKE; MOTOR AREAS; NOGO-A; ANGIOGENESIS; RATS; PROTEIN; GENE; NEUROGENESIS;
D O I
10.1007/s00401-011-0914-z
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, which also has neuroprotective activity. In view of these dual actions on vessels and neurons, we were interested whether VEGF promotes long distance axonal plasticity in the ischemic brain. Herein, we show that VEGF promotes neurological stroke recovery in mice when delivered in a delayed way starting 3 days after middle cerebral artery occlusion. Using anterograde tract-tracing experiments that we combined with histochemical and molecular biological studies, we demonstrate that although VEGF promoted angiogenesis predominantly in the ischemic hemisphere, pronounced axonal sprouting was induced by VEGF in the contralesional, but not the ipsilesional corticobulbar system. Corticobulbar plasticity was accompanied by the deactivation of the matrix metalloproteinase MMP9 in the lesioned hemisphere and the transient downregulation of the axonal growth inhibitors NG2 proteoglycan and brevican and the guidance molecules ephrin B1/2 in the contralesional hemisphere. The regulation of matrix proteinases, growth inhibitors, and guidance molecules offers insights how brain plasticity is controlled in the ischemic brain.
引用
收藏
页码:273 / 284
页数:12
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