Vascular changes after stroke in the rat: a longitudinal study using optimized magnetic resonance imaging

Abstract

During stroke, the reduction of blood flow leads to undersupply of oxygen and nutrients and, finally, to cell death, but also to upregulation of pro-angiogenic molecules and vascular remodeling. However, the temporal profile of vascular changes after stroke is still poorly understood. Here, we optimized steady-state contrast-enhanced magnetic resonance imaging (SSCE MRI) and followed the dynamic changes in vascular architecture for up to 4 weeks after transient middle cerebral artery occlusion (MCAO) in rats. Using MRI diffusion measurements and the changes of transversal relaxation rates ΔR2 and ΔR2* after injection of a superparamagnetic contrast agent, SSCE MRI provided several hemodynamic parameters: relative cerebral blood volume (rCBV), rCBV in small vessels, microvascular density, and relative vessel size. Six rats underwent SSCE MRI before MCAO and at 7, 14, 21 and 28 days after surgery. 5-Bromo-2'deoxyuridine (BrdU) was injected between days 2 and 7 to label proliferating cells during this time. SSCE MRI depicted a decrease in microvessel density and an increase in vessel size in the ischemic striatum after stroke. A persistently decreased MRI vessel density was confirmed with histology at 28 days. BrdU + endothelial cells were found in regions close to the infarct indicating endothelial cell proliferation during the first week after MCAO; however, late-stage angiogenesis, as would be reflected by increased vessel density, was not detected. The optimized SSCE MRI protocol was used to follow spatio-temporal changes of important vessel characteristics, which may contribute to a better understanding of the role of angiogenesis at different stages after stroke.

Microvascular Plasticity After Experimental Stroke: A Molecular and MRI Study

“…1a) confirms the occurrence of angiogenesis in the damaged hemisphere. These results are in line with Lin et al and Strbian et al [21,30] but not with Boehm-Sturm et al [24] who did not detect change in microvessel density or caliber. This discrepancy might be ascribed to difference in MRI methodology (use of multi-echo vs. single-echo to map change in T 2 ) or animal model (60- vs. 90-min transient MCAo).…”

“…We observed a decreased vascular density with increased CBV and vessel caliber (VSI) in conjunction with a major BBB permeability at D3. Similar evolutions of CBV and perfused vessel caliber have been reported in a three-vessel occlusion model [21] and in an MCAo model (transient 60 min) [24]. For BBB permeability, similar observations were obtained in an MCAo model (transient 90 min) [30].…”

“…Data have been collected using a transient (60 min) three-vessel occlusion model in rats [21], a permanent embolic stroke model in rats [22,23], and a transient (60 min) intraluminal occlusion model in rats [24]. …”

Gaining Mechanistic Insights into Cell Therapy Using Magnetic Resonance Imaging

“…The characterization of the microenvironment can be achieved using advanced MRI techniques, such as diffusion MR histology and microtractography [23], as well as blood flow measurements and microvasculature [24]. However, in contrast, to define the determinants of the transplanted cell therapeutic efficacy, their distribution within the tissue and their sphere of spatial activity require serial monitoring.…”

MRI Visualization of Whole Brain Macro- and Microvascular Remodeling in a Rat Model of Ischemic Stroke: A Pilot Study

“…To obtain morphological information about the microvasculature, vessel size index (VSI) and microvessel density indices (Q and MVD) can be measured. VSI, Q, and MVD values obtained through alteration of transverse relaxation rates (ΔR 2 and ΔR 2 * ) due to the administration of contrast agent 20-23 can be used to map morphological microvascular alterations after ischemic stroke [24][25][26][27][28][29][30] . As arteriogenesis and angiogenesis are likely to correlate with recovery after ischemic stroke, the association between vessel morphology and corresponding tissue ischemic edema status (via apparent diffusion coefficient [ADC]) can be verified by simultaneous assessment of total macro-and microvascular remodeling in the ischemic brain.In this pilot study, we performed dual contrast MRI using superparamagnetic iron oxide nanoparticles (SPION) as a single contrast agent 18,19 .…”