Original Article
Journal of Cerebral Blood Flow & Metabolism (2008) 28, 1440–1448; doi:10.1038/jcbfm.2008.33; published online 16 April 2008
Magnetic resonance imaging investigation of axonal remodeling and angiogenesis after embolic stroke in sildenafil-treated rats
This work was supported by NINDS Grants PO1 NS23393, PO1 NS42345, RO1 NS38292, RO1 NS48349, RO1 NS43324, and HL64766.
Guangliang Ding1, Quan Jiang1, Lian Li1, Li Zhang1, Zheng Gang Zhang1, Karyn A Ledbetter1, Swayamprava Panda1, Siamak P N Davarani1,2, Hemanthkumar Athiraman1,3, Qingjiang Li1, James R Ewing1 and Michael Chopp1,3
- 1Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA
- 2Department of Electrical Engineering, University of Michigan, Ann Arbor, Michigan, USA
- 3Department of Physics, Oakland University, Rochester, Michigan, USA
Correspondence: Dr M Chopp, Henry Ford Hospital, Neurology Department, E&R 3056, 2799 West Grand Boulevard, Detroit MI 48202, USA. E-mail: chopp@neuro.hfh.edu
Received 31 January 2008; Revised 17 March 2008; Accepted 24 March 2008; Published online 16 April 2008.
Abstract
Interaction between angiogenesis and axonal remodeling after stroke was dynamically investigated by MRI in rats with or without sildenafil treatments. Male Wistar rats were subjected to embolic stroke and treated daily with saline (n=10) or with sildenafil (n=11) initiated at 24 h and subsequently for 7 days after onset of ischemia. T2*-weighted imaging, cerebral blood flow (CBF), and diffusion tensor imaging (DTI) measurements were performed from 24 h to 6 weeks after embolization. T2* and fractional anisotropy (FA) maps detected angiogenesis and axonal remodeling after stroke, respectively, starting from 1 week in sildenafil-treated rats. Areas demarcated by MRI with enhanced angiogenesis, elevated local CBF, and augmented axonal remodeling were spatially and temporally matched, and FA values were significantly correlated with the corresponding CBF values (R=0.66, P<4
10-5) at 6 weeks after stroke. Axonal projections were reorganized along the ischemic boundary after stroke. These MRI measurements, confirmed by histology, showed that sildenafil treatment simultaneously enhanced angiogenesis and axonal remodeling, which were MRI detectable starting from 1 week after stroke in rats. The spatial and temporal consistency of MRI metrics and the correlation between FA and local CBF suggest that angiogenesis, by elevating local CBF, promotes axonal remodeling after stroke.
Keywords:
angiogenesis, axonal remodeling, cerebral blood flow, diffusion tensor imaging, embolic stroke, magnetic resonance imaging
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