BACKGROUND AND PURPOSE: Occlusion in cerebral vessels results in ischemic stroke and is followed by proliferation of microvessels, ie, angiogenesis. The process is particularly marked in the border zone of the infarct, known as the ischemic penumbra. This increase in vascularization is likely to be caused by the action of angiogenic factors, such as TGF-beta 1, which is a powerful regulator of angiogenesis. METHODS: In this study we examined 10 brain samples from patients who suffered from ischemic stroke for the expression of mRNA encoding TGF-beta 1. RESULTS: The ischemic penumbra contained the highest levels of TGF-beta 1 mRNA, whereas the normal contralateral hemispheres had the least (P < .001, Mann-Whitney U test). Unlike those from normal brain, protein extracts from infarcted tissue contained active TGF-beta 1 as a 25-kD band in Western blot analysis. Extracts from the penumbra also contained a 12.5-kD isoform of TGF-beta 1. Both penumbra and infarct contained TGF-beta 1 immunoreactive products as assessed with immunohistochemistry, whereas very weak staining was observed in the contralateral hemisphere. CONCLUSIONS: These results suggest that TGF-beta 1 is important in the pathogenesis of the angiogenic response in ischemic brain tissue and its modulation may be used for therapeutic purposes.
BACKGROUND AND PURPOSE: Occlusion in cerebral vessels results in ischemic stroke and is followed by proliferation of microvessels, ie, angiogenesis. The process is particularly marked in the border zone of the infarct, known as the ischemic penumbra. This increase in vascularization is likely to be caused by the action of angiogenic factors, such as TGF-beta 1, which is a powerful regulator of angiogenesis. METHODS: In this study we examined 10 brain samples from patients who suffered from ischemic stroke for the expression of mRNA encoding TGF-beta 1. RESULTS: The ischemic penumbra contained the highest levels of TGF-beta 1 mRNA, whereas the normal contralateral hemispheres had the least (P < .001, Mann-Whitney U test). Unlike those from normal brain, protein extracts from infarcted tissue contained active TGF-beta 1 as a 25-kD band in Western blot analysis. Extracts from the penumbra also contained a 12.5-kD isoform of TGF-beta 1. Both penumbra and infarct contained TGF-beta 1 immunoreactive products as assessed with immunohistochemistry, whereas very weak staining was observed in the contralateral hemisphere. CONCLUSIONS: These results suggest that TGF-beta 1 is important in the pathogenesis of the angiogenic response in ischemic brain tissue and its modulation may be used for therapeutic purposes.
Authors: Richard Milner; Stephanie Hung; Bernadette Erokwu; Paula Dore-Duffy; Joseph C LaManna; Gregory J del Zoppo Journal: Mol Cell Neurosci Date: 2008-02-13 Impact factor: 4.314