Magnetic resonance imaging investigation of axonal remodeling and angiogenesis after embolic stroke in sildenafil-treated rats
Open accessAbstract
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. T* 2 -weighted imaging, cerebral blood flow (CBF), and diffusion tensor imaging (DTI) measurements were performed from 24 h to 6 weeks after embolization. T* 2 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.
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In rodents, survival of ischaemic pyramidal tract axons can be improved by pharmacological and cell-based treatments.
“In rodents, the survival of ischaemic pyramidal tract axons can be improved by pharmacological and cell-based treatments.26–28”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [27]
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- Authors
- Ding, G., Jiang, Q., Li, L., Zhang, L., Zhang, Z. G., Ledbetter, K. A., Panda, S., Davarani, S. P., Athiraman, H., Li, Q., Ewing, J. R., & Chopp, M.
- Affiliations
- Henry Ford Health (US)
- Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA
- Corresponding author
- Chopp, Michael
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2008-04-16
- Volume
- 28
- Issue
- 8
- Pages
- 1440-1448
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC2575653
- OpenAlex
- W2032477901
- Cited by
- 138
- References
- 36
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 12 · 2017: 9 · 2016: 9 · 2015: 12 · 2014: 6 · 2013: 9 · 2012: 12
- FWCI
- 9.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 64766, R01HL064766)
- National Institute of Neurological Disorders and Stroke (P01NS23393, R01NS062832, P01NS023393, P01NS42345, P50NS023393, R01 NS48349, R01NS043324, R01 NS 38292, R01NS048349, P01NS042345, R01NS038292, R01 NS 43324)
- National Center for Research Resources (S10RR019245)
- Topics
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- embolic stroke, sildenafil, axonal remodeling, angiogenesis, cerebral blood flow, fractional anisotropy, diffusion tensor imaging, T2-weighted imaging, stroke recovery, neurovascular interactions
- MeSH terms
- Sildenafil Citrate, Animals, Axons, Brain, Cerebrovascular Circulation, Male, Piperazines, Purines, Sulfones, Time Factors, Vasodilator Agents, Rats, Wistar, Magnetic Resonance Angiography, Neovascularization, Physiologic, Recovery of Function, Stroke, Intracranial Embolism, Rats
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