Collateral density, remodeling, and VEGF-A expression differ widely between mouse strains

Chalothorn, Dan; Clayton, Jason A.; Zhang, Hua; Pomp, Daniel; Faber, James E.

doi:10.1152/physiolgenomics.00047.2007

Cited by 188 publications

(308 citation statements)

References 62 publications

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“…Each hemisphere was divided into six grids of equal area and the total number of collaterals between the anterior, posterior, and middle cerebral arteries were counted manually (Chalothorn et al, 2007). A collateral was defined as an anastomosis between MCA and anterior or posterior cerebral arteries.…”

Section: Measurement Of Remodeling Indicesmentioning

confidence: 99%

Vascular Protection in Diabetic Stroke: Role of Matrix Metalloprotease-Dependent Vascular Remodeling

Elgebaly

Prakash

et al. 2010

J Cereb Blood Flow Metab

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Temporary focal ischemia causes greater hemorrhagic transformation (HT) in diabetic Goto-Kakizaki (GK) rats, a model with increased cerebrovascular matrix metalloprotease (MMP) activity and tortuosity. The objective of the current study was to test the hypotheses that (1) diabetes-induced cerebrovascular remodeling is MMP dependent and (2) prevention of vascular remodeling by glucose control or MMP inhibition reduces HT in diabetic stroke. Control and GK rats were treated with vehicle, metformin, or minocycline for 4 weeks, and indices of remodeling including vascular tortuosity index, lumen diameter, number of collaterals, and middle cerebral artery (MCA) MMP activity were measured. Additional animals were subjected to 3 hours MCA occlusion/21 hours reperfusion, and infarct size and HT were evaluated as indices of neurovascular injury. All remodeling markers including MMP-9 activity were increased in diabetes. Infarct size was smaller in minocycline-treated animals. Both metformin and minocycline reduced vascular remodeling and severity of HT in diabetes. These results provide evidence that diabetes-mediated stimulation of MMP-9 activity promotes cerebrovascular remodeling, which contributes to greater HT in diabetes. Metformin and minocycline offer vascular protection, which has important clinical implications for diabetes patients who are at a fourfold to sixfold higher risk for stroke.

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Section: Measurement Of Remodeling Indicesmentioning

confidence: 99%

Vascular Protection in Diabetic Stroke: Role of Matrix Metalloprotease-Dependent Vascular Remodeling

Elgebaly

Prakash

et al. 2010

J Cereb Blood Flow Metab

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“…Whether differences in collateral number or diameter, secondary to natural genetic variation or environmental factors, exist and contribute to this variability is unknown. We previously reported that the C57BL/6 and BALB/c mouse strains exhibit large differences in the density and diameter of native collaterals in several tissues, including the cerebral cortex, which are accompanied by large differences in infarct volume after occlusion (Chalothorn et al, 2007). We also identified two genes, Vegfa and Clic4, whose level of expression strongly influence-in multiple tissues-the formation of the collateral circulation, which occurs perinatally in mice (collaterogenesis), and severity of stroke (Clayton et al, 2008;).…”

Section: Introductionmentioning

confidence: 99%

Wide Genetic Variation in the Native Pial Collateral Circulation is a Major Determinant of Variation in Severity of Stroke

Zhang

Prabhakar

Sealock

et al. 2010

J Cereb Blood Flow Metab

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228

383

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Severity of stroke varies widely among individuals. Whether differences in the extent of the native (preexisting) pial collateral circulation exist and contribute to this variability is unknown. We addressed these questions and probed for potential genetic contributions using morphometric analysis of the collateral circulation in 15 inbred mouse strains recently shown to exhibit wide differences in infarct volume. Morphometrics were determined in the unligated left hemisphere (for native collaterals) and ligated right hemisphere (for remodeled collaterals) 6 days after permanent middle cerebral artery (MCA) occlusion. Variation among strains in native collateral number, diameter, MCA, anterior cerebral artery (ACA), and posterior cerebral artery (PCA) tree territories were, respectively: 56-fold, 3-fold, 42%, 56%, and 61%. Collateral length (P < 0.001) and the number of penetrating arterioles branching from them also varied (P < 0.05). Infarct volume correlated inversely with collateral number (P < 0.0001), diameter (P < 0.0001), and penetrating arteriole number (P < 0.05) and directly with MCA territory (P < 0.05). Relative collateral conductance and MCA territory, when factored together, strongly predicted infarct volume (P < 0.0001). Outward remodeling of collaterals in the ligated hemisphere varied B3-fold. These data show that the extent of the native pial collateral circulation and collateral remodeling after obstruction vary widely with genetic background, and suggest that this variability, due to natural polymorphisms, is a major contributor to variability in infarct volume.

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“…Visualization of vessels, therefore, can be accomplished either by filling with a fluorescent substance (e.g. PU4ii: a polyurethane resin 3 , or fluorescein infused dextran 26 ), or through non-filling methods, such as whole-mount immunodetection via either fluorescence or a histochemical chromogenic precipitate (e.g. BCIP/NBT) 23 .…”

Section: Discussionmentioning

confidence: 99%

Retrograde Perfusion and Filling of Mouse Coronary Vasculature as Preparation for Micro Computed Tomography Imaging

Weyers

Carlson

Murry

et al. 2012

JoVE

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Visualization of the vasculature is becoming increasingly important for understanding many different disease states. While several techniques exist for imaging vasculature, few are able to visualize the vascular network as a whole while extending to a resolution that includes the smaller vessels 1,2 . Additionally, many vascular casting techniques destroy the surrounding tissue, preventing further analysis of the sample [3][4][5] . One method which circumvents these issues is micro-Computed Tomography (μCT). μCT imaging can scan at resolutions <10 microns, is capable of producing 3D reconstructions of the vascular network, and leaves the tissue intact for subsequent analysis (e.g., histology and morphometry) [6][7][8][9][10][11] . However, imaging vessels by ex vivo μCT methods requires that the vessels be filled with a radiopaque compound. As such, the accurate representation of vasculature produced by μCT imaging is contingent upon reliable and complete filling of the vessels. In this protocol, we describe a technique for filling mouse coronary vessels in preparation for μCT imaging.Two predominate techniques exist for filling the coronary vasculature: in vivo via cannulation and retrograde perfusion of the aorta (or a branch off the aortic arch) [12][13][14] , or ex vivo via a Langendorff perfusion system [15][16][17] . Here we describe an in vivo aortic cannulation method which has been specifically designed to ensure filling of all vessels. We use a low viscosity radiopaque compound called Microfil which can perfuse through the smallest vessels to fill all the capillaries, as well as both the arterial and venous sides of the vascular network. Vessels are perfused with buffer using a pressurized perfusion system, and then filled with Microfil. To ensure that Microfil fills the small higher resistance vessels, we ligate the large branches emanating from the aorta, which diverts the Microfil into the coronaries. Once filling is complete, to prevent the elastic nature of cardiac tissue from squeezing Microfil out of some vessels, we ligate accessible major vascular exit points immediately after filling. Therefore, our technique is optimized for complete filling and maximum retention of the filling agent, enabling visualization of the complete coronary vascular network -arteries, capillaries, and veins alike. Video LinkThe video component of this article can be found at http://www.jove.com/video/3740/ Protocol 1. Preparations before starting Paraformaldehyde (PFA) in PBS, respectively. 2. Prepare a 1/2cc Insulin Syringe (with a permanently attached 29G ½" needle) by filling it with 0.1 ml of 1:100 Heparin (5000U/ml stock) and bending the needle to ~120 degree angle with the bevel up. Do the same with a 1 ml syringe (with a 26G ½" needle) filled with 0.3 ml saturated KCl solution.2. Exposing the heart and cannulating the aorta 1. Anesthetize the mouse using your anesthetic of choice. (We use an overdose of a Ketamine/Xylazine mixture: IP injection of 130 mg/kg Ketamine and 8.8 mg/kg Xylazine in saline.) 2...

show abstract

Collateral density, remodeling, and VEGF-A expression differ widely between mouse strains

Cited by 188 publications

References 62 publications

Vascular Protection in Diabetic Stroke: Role of Matrix Metalloprotease-Dependent Vascular Remodeling

Vascular Protection in Diabetic Stroke: Role of Matrix Metalloprotease-Dependent Vascular Remodeling

Wide Genetic Variation in the Native Pial Collateral Circulation is a Major Determinant of Variation in Severity of Stroke

Retrograde Perfusion and Filling of Mouse Coronary Vasculature as Preparation for Micro Computed Tomography Imaging

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