scholarly journals Angiopoietin-2 is Vasoprotective in the Acute Phase of Cerebral Ischemia

2012 ◽  
Vol 33 (3) ◽  
pp. 389-395 ◽  
Author(s):  
Léna Marteau ◽  
Samuel Valable ◽  
Didier Divoux ◽  
Simon A Roussel ◽  
Omar Touzani ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Acute Phase ◽  
Focal Cerebral Ischemia ◽  
Neurovascular Unit ◽  
Protective Role ◽  
Lesion Volume ◽  
Ischemic Lesion ◽  
Vessel Growth ◽  
Angiopoietin 2

Most forms of cerebral ischemia are characterized by damage to the entire neurovascular unit, which leads to an increase in the permeability of the blood–brain barrier (BBB). In response to permanent focal cerebral ischemia in mice, we detected an early concomitant increase in the expression of the vascular endothelial growth factor (VEGF), a key inducer of vascular leakage and pathological blood vessel growth, and of angiopoietin-2 (Ang2), which is closely associated with VEGF in vascular remodeling. Thus, the aim of this study was to evaluate the role of Ang2 alone, or in combination with VEGF, in the acute phase of cerebral ischemia. The effect of these angiogenic factors on the ischemic lesion volume was evaluated by magnetic resonance imaging. We observed that timely administration of VEGF exacerbates ischemic damage. In contrast, Ang2 decreases the ischemic volume and this beneficial effect is maintained in the presence of VEGF. This investigation reports, for the first time, a protective role of Ang2 following cerebral ischemia, an action associated with a reduced BBB permeability. We propose that Ang2 represents a pertinent molecular target for the treatment of cerebral ischemia since acute brain damage may be limited by a pharmacological protection of the vascular compartment.

scholarly journals Involvement of caveolin-1 in neurovascular unit remodeling after stroke: Effects on neovascularization and astrogliosis

2018 ◽  
Vol 40 (1) ◽  
pp. 163-176 ◽  
Author(s):  
Camille Blochet ◽  
Lara Buscemi ◽  
Tifenn Clément ◽  
Sabrina Gehri ◽  
Jérôme Badaut ◽  
...  
Keyword(s):  
Neurovascular Unit ◽  
Protective Role ◽  
Artery Occlusion ◽  
Lesion Volume ◽  
Post Injury ◽  
Caveolin 1 ◽  
Molecular Events ◽  
Cerebral Artery Occlusion ◽  
Precise Role

Complex cellular and molecular events occur in the neurovascular unit after stroke, such as blood–brain barrier (BBB) dysfunction and inflammation that contribute to neuronal death, neurological deterioration and mortality. Caveolin-1 (Cav-1) has distinct physiological functions such as caveolae formation associated with endocytosis and transcytosis as well as in signaling pathways. Cav-1 has been proposed to be involved in BBB dysfunction after brain injury; however, its precise role is poorly understood. The goal of this study was to characterize the expression and effect of Cav-1 deletion on outcome in the first week in a transient Middle Cerebral Artery Occlusion stroke model. We found increased Cav-1 expression in new blood vessels in the lesion and in reactive astrocytes in the peri-lesion areas. In Cav-1 KO mice, the lesion volume was larger and the behavioral outcome worse than in WT mice. Cav-1 KO mice exhibited reduced neovascularization and modified astrogliosis, without formation of a proper glial scar around the lesion at three days post injury, coinciding with aggravated outcomes. Altogether, these results point towards a potential protective role of endogenous Cav-1 in the first days after ischemia by promoting neovascularization, astrogliosis and scar formation.

scholarly journals Protective role of isoflurane pretreatment in rats with focal cerebral ischemia and the underlying molecular mechanism

2012 ◽  
Vol 12 (1) ◽  
pp. 675-683 ◽  
Author(s):  
ZHIBIN XIAO ◽  
PENGCHENG REN ◽  
YANG CHAO ◽  
QIANYUN WANG ◽  
JIANKE KUAI ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Molecular Mechanism ◽  
Focal Cerebral Ischemia ◽  
Protective Role

scholarly journals Secondary Deterioration of Apparent Diffusion Coefficient After 1-Hour Transient Focal Cerebral Ischemia in Rats

2000 ◽  
Vol 20 (10) ◽  
pp. 1474-1482 ◽  
Author(s):  
Laszlo Olah ◽  
Stefan Wecker ◽  
Mathias Hoehn
Keyword(s):  
Diffusion Coefficient ◽  
Energy Metabolism ◽  
Cerebral Ischemia ◽  
Apparent Diffusion Coefficient ◽  
Focal Cerebral Ischemia ◽  
Lesion Volume ◽  
Ischemic Lesion ◽  
Early Reperfusion ◽  
Transient Focal Cerebral Ischemia ◽  
Apparent Diffusion

Recent investigations on transient focal cerebral ischemia suggested recovery of energy metabolism during early reperfusion, but followed by secondary energy failure. As disturbances of energy metabolism are reflected by changes of the apparent diffusion coefficient (ADC) of water, the aim of the current study was to follow the dynamics of the ADC during 1 hour of middle cerebral artery occlusion (MCAO) and 10 hours of reperfusion. The right MCA was occluded in male Wistar rats inside the magnet using a remotely controlled thread occlusion model. Diffusion-, perfusion-, and T2-weighted images were performed repetitively, and ADC, perfusion, and T2maps were calculated and normalized to the respective preischemic value. The lesion volume at each time point was defined by ADC < 80% of control. At the end of 1-hour MCAO the hemispheric lesion volume was 22.3 ± 9.0%; it decreased to 6.4 ± 5.7% in the first 2 hours of reperfusion ( P < 0.01), but then increased again, and by the end of 10 hours of reperfusion reached 17.3 ± 9.3%. The mean relative ADC in the end ischemic lesion volume significantly improved within 2 hours of reperfusion (from 65.7 ± 1.2% to 90.1 ± 6.7% of control), but later declined and decreased to 75.4 ± 7.3% of control by the end of the experiment. Pixels with secondary deterioration of ADC showed a continuous increase of T2value during the first 2 hours of reperfusion in spite of ADC improvement, indicating improving cytotoxic, but generation of vasogenic edema during early reperfusion. A significant decrease of the perfusion level was not observed during 10 hours of recirculation. The authors conclude that the improvement of ADC in the early phase of reperfusion may be followed by secondary deterioration that was not caused by delayed hypoperfusion.

Protective role of hematopoietic prostaglandin D synthase in transient focal cerebral ischemia in mice

Neuroscience ◽  
2009 ◽  
Vol 163 (1) ◽  
pp. 296-307 ◽  
Author(s):  
M. Liu ◽  
N. Eguchi ◽  
Y. Yamasaki ◽  
Y. Urade ◽  
N. Hattori ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Protective Role ◽  
Transient Focal Cerebral Ischemia ◽  
Prostaglandin D Synthase

scholarly journals Evidence for a protective role of metallothionein-1 in focal cerebral ischemia

1999 ◽  
Vol 96 (22) ◽  
pp. 12870-12875 ◽  
Author(s):  
M. van Lookeren Campagne ◽  
H. Thibodeaux ◽  
N. van Bruggen ◽  
B. Cairns ◽  
R. Gerlai ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Protective Role

scholarly journals A novel voxel-wise lesion segmentation technique on 3.0-T diffusion MRI of hyperacute focal cerebral ischemia at 1 h after permanent MCAO in rats

2017 ◽  
Vol 38 (8) ◽  
pp. 1371-1383 ◽  
Author(s):  
Chi-Hoon Choi ◽  
Kyung Sik Yi ◽  
Sang-Rae Lee ◽  
Youngjeon Lee ◽  
Chang-Yeop Jeon ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Region Of Interest ◽  
Artery Occlusion ◽  
Lesion Segmentation ◽  
Ischemic Lesion ◽  
Segmentation Technique ◽  
Apparent Diffusion ◽  
Relative Threshold ◽  
Cerebral Ischemic

To assess hyperacute focal cerebral ischemia in rats on 3.0-Tesla diffusion-weighted imaging (DWI), we developed a novel voxel-wise lesion segmentation technique that overcomes intra- and inter-subject variation in apparent diffusion coefficient (ADC) distribution. Our novel technique involves the following: (1) intensity normalization including determination of the optimal type of region of interest (ROI) and its intra- and inter-subject validation, (2) verification of focal cerebral ischemic lesions at 1 h with gross and high-magnification light microscopy of hematoxylin-eosin (H&E) pathology, (3) voxel-wise segmentation on ADC with various thresholds, and (4) calculation of dice indices (DIs) to compare focal cerebral ischemic lesions at 1 h defined by ADC and matching H&E pathology. The best coefficient of variation was the mode of the left hemisphere after normalization using whole left hemispheric ROI, which showed lower intra- (2.54 ± 0.72%) and inter-subject (2.67 ± 0.70%) values than the original. Focal ischemic lesion at 1 h after middle cerebral artery occlusion (MCAO) was confirmed on both gross and microscopic H&E pathology. The 83 relative threshold of normalized ADC showed the highest mean DI (DI = 0.820 ± 0.075). We could evaluate hyperacute ischemic lesions at 1 h more reliably on 3-Tesla DWI in rat brains.

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