SB 234551 selective ETA receptor antagonism: Perfusion/Diffusion MRI used to define treatable stroke model, time to treatment and mechanism of protection

Legos, Jeffrey J.; Lenhard, Stephen C.; Haimbach, Robin E.; Schaeffer, Thomas; Bentley, Ross; McVey, Matthew; Chandra, Sudeep; Irving, Elaine; Parsons, Andrew A.; Barone, Frank C.

doi:10.1016/j.expneurol.2008.03.011

Cited by 43 publications

(37 citation statements)

References 72 publications

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“…First, we directed our study toward SHR, the most common strain used in studies on essential arterial hypertension and their normotensive controls, the WKY. In SHR, and in accordance with the study of Legos et al (2008), ADC-defined lesions were greater than those of normotensive rats. Moreover, our study revealed that the ADC-defined lesion was greater even in the 30 minutes after occlusion in comparison to WKY ( Figure 4A).…”

Section: Discussionsupporting

confidence: 85%

“…This approach has been shown to provide equivalent information on the perfusion deficit as quantified through the use of continuous arterial spin labeling (Bråtane et al, 2010). The volume of initially hypoperfused tissue remained essentially stable over time after ischemia in normotensive animals (ANOVA repeated measures, time effect: P = 0.44) as has been previously described (Legos et al, 2008;Bardutzky et al, 2005). However in SHR, hypoperfusion expanded with time (ANOVA repeated measures, time effect: P < 0.05) and was greater than that of WKY at 240 minutes after the occlusion, suggesting a failure of collateral circulation in SHR.…”

Section: Discussionsupporting

confidence: 52%

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Impact of Genetic and Renovascular Chronic Arterial Hypertension on the Acute Spatiotemporal Evolution of the Ischemic Penumbra: A Sequential Study with MRI in the Rat

Letourneur

Roussel

Toutain

et al. 2010

J Cereb Blood Flow Metab

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Although chronic arterial hypertension (CAH) increases the risk of stroke and the severity of the resultant lesion, it is rarely integrated in preclinical studies. Here, we analyzed the impact of CAH on the acute spatiotemporal evolution of the ischemic penumbra as defined by the perfusion-weighted imaging/diffusion-weighted imaging mismatch. Sequential 7T-MRI examinations were performed from 30 minutes up to 4 hours after permanent cerebral ischemia in genetically hypertensive rats (spontaneously hypertensive rats, SHR), renovascular-hypertensive rats (RH-WKY), and their normotensive controls (Wistar-Kyoto rats, WKY). The apparent diffusion coefficient (ADC)-defined lesion was larger in hypertensive rats than in normotensive animals as early as 30 minutes after the ischemia. The ischemic penumbra was smaller in both genetically and renovascular-hypertensive rats (at 30 minutes; SHR = 66 ± 25 mm 3 , RH-WKY = 55 ± 17 mm 3 versus WKY = 117 ± 14 mm 3 ; P < 0.008) and there was no significant difference between the perfusion deficit and ADC lesion (mismatch definition of penumbra) as early as 90 minutes after the occlusion. Genetic hypertension and induced renovascular hypertension resulted in larger lesion and smaller penumbra that vanished rapidly. These data support the need to integrate CAH in preclinical studies relative to the treatment of stroke, as failure to do so may lead to preclinical results nonpredictive of clinical trials, which include hypertensive patients.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 52%

Impact of Genetic and Renovascular Chronic Arterial Hypertension on the Acute Spatiotemporal Evolution of the Ischemic Penumbra: A Sequential Study with MRI in the Rat

Letourneur

Roussel

Toutain

et al. 2010

J Cereb Blood Flow Metab

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“…55,56 In this regard, ET receptor antagonism improves neurological outcome in animal models of stroke and Alzheimer disease. 57,58 Thus, our observation that ET-1 treatment induced neurological impairments in PbN-infected mice was not surprising. The present study corroborates the potential use of ET-1 as a therapeutic target in patients with CM.…”

mentioning

confidence: 71%

Endothelin-1 Treatment Induces an Experimental Cerebral Malaria–Like Syndrome in C57BL/6 Mice Infected with Plasmodium berghei NK65

Martins

Freeman

Ndunge

et al. 2016

The American Journal of Pathology

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Plasmodium berghei ANKA infection of C57BL/6 mice is a widely used model of experimental cerebral malaria (ECM). By contrast, the nonneurotropic P. berghei NK65 (PbN) causes severe malarial disease in C57BL/6 mice but does not cause ECM. Previous studies suggest that endothelin-1 (ET-1) contributes to the pathogenesis of ECM. In this study, we characterize the role of ET-1 on ECM vascular dysfunction. Mice infected with 10 6 PbN-parasitized red blood cells were treated with either ET-1 or saline from 2 to 8 days postinfection (dpi). Plasmodium berghei ANKAeinfected mice served as the positive control. ET-1e treated PbN-infected mice exhibited neurological signs, hypothermia, and behavioral alterations characteristic of ECM, dying 4 to 8 dpi. Parasitemia was not affected by ET-1 treatment. Saline-treated PbNinfected mice did not display ECM, surviving until 12 dpi. ET-1etreated PbN-infected mice displayed leukocyte adhesion to the vascular endothelia and petechial hemorrhages throughout the brain at 6 dpi. Intravital microscopic images demonstrated significant brain arteriolar vessel constriction, decreased functional capillary density, and increased blood-brain barrier permeability. These alterations were not present in either ET-1etreated uninfected or saline-treated PbN-infected mice. In summary, ET-1 treatment of PbN-infected mice induced an ECM-like syndrome, causing brain vasoconstriction, adherence of activated leukocytes in the cerebral microvasculature, and blood-brain barrier leakage, indicating that ET-1 is involved in the genesis of brain microvascular alterations that are the hallmark of ECM. (Am J Pathol 2016 http://dx

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“…Second, studies in comorbid animals are included in the quality score, but there is no evidence that studying the effects of treatments in such animals is of any more value than doing so in young, healthy animals, a point also discussed in the original article describing this methodology. 6 There is little evidence of a penumbra in comorbid animals, 7 even though one is frequently identified in stroke patients. 8 Third, not making a statement regarding any potential conflict of interest scores ''0,'' but the score given for a reported conflict of interest is not clear.…”

Section: To the Editormentioning

confidence: 99%

Interleukin-1 Receptor Antagonist in Animal Models of Stroke: A Fair Summing Up?

Parry‐Jones

Boutin

McColl

et al. 2010

Journal of Stroke and Cerebrovascular Diseases

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SB 234551 selective ETA receptor antagonism: Perfusion/Diffusion MRI used to define treatable stroke model, time to treatment and mechanism of protection

Cited by 43 publications

References 72 publications

Impact of Genetic and Renovascular Chronic Arterial Hypertension on the Acute Spatiotemporal Evolution of the Ischemic Penumbra: A Sequential Study with MRI in the Rat

Impact of Genetic and Renovascular Chronic Arterial Hypertension on the Acute Spatiotemporal Evolution of the Ischemic Penumbra: A Sequential Study with MRI in the Rat

Endothelin-1 Treatment Induces an Experimental Cerebral Malaria–Like Syndrome in C57BL/6 Mice Infected with Plasmodium berghei NK65

Interleukin-1 Receptor Antagonist in Animal Models of Stroke: A Fair Summing Up?

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