Differences in the Evolution of the Ischemic Penumbra in Stroke-Prone Spontaneously Hypertensive and Wistar-Kyoto Rats

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Perfusion-diffusion (perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI)) mismatch is used to identify penumbra in acute stroke. However, limitations in penumbra detection with mismatch are recognized, with a lack of consensus on thresholds, quantification and validation of mismatch. We determined perfusion and diffusion thresholds from final infarct in the clinically relevant spontaneously hypertensive stroke-prone (SHRSP) rat and its normotensive control strain, Wistar-Kyoto (WKY) and compared three methods for penumbra calculation. After permanent middle cerebral artery occlusion (MCAO) (WKY n = 12, SHRSP n = 15), diffusion-weighted (DWI) and perfusion-weighted (PWI) images were obtained for 4 hours post stroke and final infarct determined at 24 hours on T 2 scans. The PWI/DWI mismatch was calculated from volumetric assessment (perfusion deficit volume minus apparent diffusion coefficient (ADC)-defined lesion volume) or spatial assessment of mismatch area on each coronal slice. The ADC-derived lesion growth provided the third, retrospective measure of penumbra. At 1 hour after MCAO, volumetric mismatch detected smaller volumes of penumbra in both strains (SHRSP: 31 ± 50 mm 3 , WKY: 22 ± 59 mm 3 , mean±s.d.) compared with spatial assessment (SHRSP: 36±15 mm 3 , WKY: 43±43 mm 3 ) and ADC lesion expansion (SHRSP: 41 ± 45 mm 3 , WKY: 65 ± 41 mm 3 ), although these differences were not statistically significant. Spatial assessment appears most informative, using both diffusion and perfusion data, eliminating the influence of negative mismatch and allowing the anatomical location of penumbra to be assessed at given time points after stroke.

Section: Discussionsupporting

confidence: 93%

Penumbra Detection using PWI/DWI Mismatch MRI in a Rat Stroke Model with and without Comorbidity: Comparison of Methods

Reid

Graham

Lopez-Gonzalez

et al. 2012

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“…Indeed, the aim of the study was not to define any absolute threshold but rather to use an objective method to delineate abnormal ADC values in which each animal constitutes its own control at each time. On the basis of this approach, our thresholds (on average a 26% reduction in ADC values) are consistent with those reported in the literature (Shen et al, 2003;McCabe et al, 2009). The same method of analysis was performed to examine the perfusion deficit based on the combination of two reliable parameters (maximal signal drop and time to peak delay) (Grandin et al, 2002).…”

Section: Discussionsupporting

confidence: 79%

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

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.

“…35 Animals were randomly allocated upon arrival from the breeding colony to normoglycemic or hyperglycemic groups by the toss of a coin. The investigator was masked to animal identity during the analysis of ADC lesion, infarct size, and immunohistochemistry.…”

Section: -Hydroxynonenal and Nitrotyrosine Immunohistochemistrymentioning

confidence: 99%

Hyperglycemia Accelerates Apparent Diffusion Coefficient-Defined Lesion Growth after Focal Cerebral Ischemia in Rats with and Without Features of Metabolic Syndrome

Tarr

Graham

Roy

et al. 2013

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Poststroke hyperglycemia is associated with a poor outcome yet clinical management is inadequately informed. We sought to determine whether clinically relevant levels of hyperglycemia exert detrimental effects on the early evolution of focal ischemic brain damage, as determined by magnetic resonance imaging, in normal rats and in those modeling the 'metabolic syndrome'. Wistar Kyoto (WKY) or fructose-fed spontaneously hypertensive stroke-prone (ffSHRSP) rats were randomly allocated to groups for glucose or vehicle administration before permanent middle cerebral artery occlusion. Diffusion-weighted imaging was carried out over the first 4 hours after middle cerebral artery occlusion and lesion volume calculated from apparent diffusion coefficient maps. Infarct volume and immunostaining for markers of oxidative stress were measured in the fixed brain sections at 24 hours. Hyperglycemia rapidly exacerbated early ischemic damage in both WKY and ffSHRSP rats but increased infarct volume only in WKY rats. There was only limited evidence of oxidative stress in hyperglycemic animals. Acute hyperglycemia, at clinically relevant levels, exacerbates early ischemic damage in both normal and metabolic syndrome rats. Management of hyperglycemia may have greatest benefit when performed in the acute phase after stroke in the absence or presence of comorbidities.