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Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia
Published on: June 8, 2019
Microvessel changes after post-ischemic benign and malignant hyperemia: experimental study in rats
Haitao Lu1, Jungong Zhao, Minghua Li
1Department of Diagnostic and Interventinal Radiololgy, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200233, PR China.
Background:
The present investigation was designed to elucidate the use of dynamic contrast enhanced perfusion MR imaging (DCE pMRI) in characterizing hyperemia, including microvessel changes, and to examine whether DCE pMRI can predict benign or malignant hyperemia.
Methods:
Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO) by intraluminal suture placement. All rats were randomized to 4 groups: MCAO for 0.5 hours followed by saline treatment (10 ml/kg; group 1); MCAO for 3 hours followed by treatment with saline (group 2) or urokinase (25000 IU/kg; group 3); and MCAO for 6 hours followed by urokinase treatment (group 4). Relative cerebral blood volume (rCBV) and relative maximum slope of increase of the signal intensity time curve (rMSI) were quantitatively analyzed from MRI. Microvessel diameter and blood-brain barrier disruption obtained by laser scanning confocal microscopy (LSCM) as well as transmission electron microscopy (TEM) were obtained for correlative study.
Results:
Benign hyperemia was noticed only in group 1; malignant hyperemia was seen in group 3. Although the rCBV of malignant hyperemia was slightly higher than in benign hyperemia (P > 0.05), the rMSI, on the other hand, was significantly lower (P < 0.05). Fluoro-isothiocyanate dextran (FITC-dextran) extravasations, marked glial end-foot process swelling, and significant vasodilatation were seen in malignant hyperemia, while no or mild leakage of FITC-dextran and slight glial end-foot process swelling occurred in benign hyperemia.
Conclusion:
Our findings indicate that DCE pMRI can characterize post-ischemic hyperemia and correlates well with microvascular damage.
Insights
Dynamic contrast-enhanced perfusion MRI (DCE pMRI) effectively characterizes post-ischemic hyperemia and microvascular changes, differentiating between benign and malignant conditions in rats.
Area of Science:
- Neuroimaging
- Vascular Biology
- Ischemic Stroke Research
Background:
- Dynamic contrast-enhanced perfusion MRI (DCE pMRI) is explored for characterizing hyperemia.
- The study investigates microvessel changes and DCE pMRI's ability to predict hyperemia type (benign vs. malignant).
Purpose of the Study:
- To elucidate the utility of DCE pMRI in characterizing post-ischemic hyperemia.
- To examine the correlation between DCE pMRI metrics and microvascular integrity.
- To determine if DCE pMRI can predict benign versus malignant hyperemia.
Main Methods:
- Middle cerebral artery occlusion (MCAO) was induced in Sprague-Dawley rats.
- Rats were assigned to groups based on occlusion duration (0.5, 3, or 6 hours) and treatment (saline or urokinase).
- Quantitative MRI analysis (rCBV, rMSI) and microscopy (LSCM, TEM) were performed for correlative studies.
Main Results:
- Benign hyperemia observed in the 0.5-hour occlusion group (saline), malignant hyperemia in the 3-hour occlusion group (urokinase).
- Malignant hyperemia showed higher rCBV (not significant) and significantly lower rMSI compared to benign hyperemia.
- Malignant hyperemia correlated with FITC-dextran extravasation, glial swelling, and vasodilation; benign hyperemia showed minimal changes.
Conclusions:
- DCE pMRI is a valuable tool for characterizing post-ischemic hyperemia.
- DCE pMRI findings correlate well with observed microvascular damage and BBB disruption.
- The study demonstrates DCE pMRI's potential in differentiating hyperemia types post-ischemia.
