Cerebral small vessel endothelial structural changes predate hypertension in stroke‐prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5‐ to 21‐week‐old rats

Bailey, Emma; Wardlaw, Joanna M.; Graham, Delyth; Dominiczak, Anna F.; Sudlow, Cathie; Smith, Colin

doi:10.1111/j.1365-2990.2011.01170.x

Cited by 74 publications

(70 citation statements)

References 37 publications

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“…Although it is not clearly identified, both PRES and ARE are likely to be based on the similar pathogenesis (endothelial damage) due to hypertension and CsA. 7,44,45 Taken together, the features of our model presented a reversible vasogenic edema which closely resembled PRES. Although, to our knowledge, FA images in PRES patients have yet to be reported, an FA increase with subsequent resolution was detected with our model, and we believe that it would be worth searching for a similar reversible FA increase in PRES patients.…”

Section: Discussionmentioning

confidence: 87%

Transient increase of fractional anisotropy in reversible vasogenic edema

Kimura-Ohba

Yang

Thompson

et al. 2016

J Cereb Blood Flow Metab

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Brain vasogenic edema, involving disruption of the blood-brain barrier, is a common pathological condition in several neurological diseases, with a heterogeneous prognosis. It is sometimes reversible, as in posterior reversible encephalopathy syndrome, but often irreversible and our current clinical tools are insufficient to reveal its reversibility. Here, we show that increased fractional anisotropy in magnetic resonance imaging is associated with the reversibility of vasogenic edema. Spontaneously, hypertensive rats-stroke prone demonstrated posterior reversible encephalopathy syndrome-like acute encephalopathy in response to high-dose cyclosporine A treatment; the deteriorating neurological symptoms and worsening scores in behavioral tests, which were seen in acute phase, dissappered after recovery by cessation of cyclosporine A. In the acute phase of encephalopathy, the fractional anisotropy and apparent diffusion coefficient increased in areas with IgG leakage. This increase of fractional anisotropy occurred in the absence of demyelination: fluid leakage into the myelinated space increased the axial, but not the radial, diffusivity, resulting in the increased fractional anisotropy. This increased fractional anisotropy returned to pre-encephalopathy values in the recovery phase. Our results highlight the importance of the fractional anisotropy increase as a marker for the reversibility of brain edema, which can delineate the brain areas for which recovery is possible. KeywordsBlood-brain barrier, brain vasogenic edema, diffusion tensor imaging, fractional anisotropy, posterior reversible encephalopathy syndrome

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Section: Discussionmentioning

confidence: 87%

Transient increase of fractional anisotropy in reversible vasogenic edema

Kimura-Ohba

Yang

Thompson

et al. 2016

J Cereb Blood Flow Metab

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“…Hypertension has numerous effects upon the brain, notably, compromise of the blood-brain barrier, 18 distributed damage to the white matter, 19 and post-stroke edema. 20 Such physiologic changes create a different milieu for the ischemia-challenged brain.…”

Section: Discussionmentioning

confidence: 99%

Hypertension and Experimental Stroke Therapies

O’Collins

Donnan

Macleod

et al. 2013

J Cereb Blood Flow Metab

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Hypertension is an established target for long-term stroke prevention but procedures for management of hypertension in acute stroke are less certain. Here, we analyze basic science data to examine the impact of hypertension on candidate stroke therapies and of anti-hypertensive treatments on stroke outcome. Methods: Data were pooled from 3,288 acute ischemic stroke experiments (47,899 animals) testing the effect of therapies on infarct size (published 1978-2010). Data were combined using meta-analysis and meta-regression, partitioned on the basis of hypertension, stroke model, and therapy. Results: Hypertensive animals were used in 10% of experiments testing 502 therapies. Hypertension was associated with lower treatment efficacy, especially in larger infarcts. Overall, anti-hypertensives did not provide greater benefit than other drugs, although benefits were evident in hypertensive animals even when given after stroke onset. Fifty-eight therapies were tested in both normotensive and hypertensive animals: some demonstrated superior efficacy in hypertensive animals (hypothermia) while others worked better in normotensive animals (tissue plasminogen activator, anesthetic agents). Discussion: Hypertension has a significant effect on the efficacy of candidate stroke drugs: standard basic science testing may overestimate the efficacy which could be reasonably expected from certain therapies and for hypertensive patients with large or temporary occlusions. Keywords: acute stroke; animal models; brain ischemia; hypertension; neuroprotection INTRODUCTION Hypertension-the elevation of blood pressure-dramatically increases the risk of stroke, with an estimated 52% of all strokes attributable to hypertension. 1 Hypertension can be controlled and numerous interventions are used in the longterm management of hypertension to prevent both first-time strokes and their recurrence. 2 Less well understood is how to tackle high blood pressure within the first 24 to 48 hours after stroke and how the presence of hypertension affects the efficacy of neuroprotective treatments administered within this period. Lowering blood pressure is not without risks, and it is generally recommended that blood pressure only be lowered if extreme; nevertheless, there is no consensus on the optimal blood pressure thresholds to trigger initiation of treatment, rates of reduction and blood pressure targets, or how hypertension should be managed with concurrent therapies such as tissue plasminogen activator. [2][3][4] Clinical trials are ongoing. 5 By examining hypertension and anti-hypertensive treatments in experimental (animal) stroke models, we may develop a better understanding of how to manage hypertension in the acute stroke setting. Knowledge of hypertension in basic science is also important in its own right. The external validity of animal testing depends upon the ability to generalize to the clinical setting: it has been a frequent criticism of preclinical drug testing that the paradigm has failed to capture the impact of important comorbidit...

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“…У КСГ и КСГПИ ЭКСПЕРИМЕНТАЛЬНО-ТЕОРЕТИЧЕСКИЕ ВОПРОСЫ были аналогичные степени АГ, но различные степени повреждения БВГМ [22]. У КСГПИ появляется повре-ждение эндотелия, белковой матрицы, глиальных клеток и миелина задолго до развития гипертензии, что ука-зывает на предрасположенность к БМЦС, с дальней-шим повреждением при развитии гипертензии [23,24]. Эти данные свидетельствуют о том, что не только АГ, но и другие факторы способствуют развитию повре-ждений БВГМ, например взаимодействие генотипа и окружающей среды.…”

Section: патологический каскад бмцс: роль артериальной гипертензии и unclassified

“…22 SHR-SPs manifest damage in the endothelium, matrix protein, glial cells, and myelin long before hypertension develops, indicating a predisposition to SVD, with further damage when hypertension does develop. 23,24 The data suggest that factors other than hypertension also contribute to the onset of WM damage, that is, gene-environment interactions. Differential gene effects can be observed in humans with WM hyperintensities (WMH).…”

Section: Pathological Cascade Of Svd: Roles Of Hypertension and Saltmentioning

confidence: 99%