Infarct volume prediction using apparent diffusion coefficient maps during middle cerebral artery occlusion and soon after reperfusion in the rat

This is the first study to assess the influence of sex on the evolution of ischaemic injury and penumbra. Permanent middle cerebral artery occlusion was induced in male (n = 9) and female (n = 10) Sprague-Dawley rats. Diffusion-weighted imaging was acquired over 4 h and infarct determined from T2 images at 24 h post-permanent middle cerebral artery occlusion. Penumbra was determined retrospectively from serial apparent diffusion coefficient lesions and T2-defined infarct. Apparent diffusion coefficient lesion volume was significantly smaller in females from 0.5 to 4 h post permanent middle cerebral artery occlusion as was infarct volume. Penumbral volume, and its loss over time, was not significantly different despite the sex difference in acute and final lesion volumes.

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

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2013.107 ◽

2013 ◽

Vol 33 (10) ◽

pp. 1556-1563 ◽

Cited By ~ 14

Author(s):

David Tarr ◽

Delyth Graham ◽

Lisa A Roy ◽

William M Holmes ◽

Christopher McCabe ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Diffusion Coefficient ◽

Apparent Diffusion Coefficient ◽

Middle Cerebral Artery ◽

Infarct Volume ◽

Artery Occlusion ◽

Ischemic Damage ◽

Apparent Diffusion ◽

Cerebral Artery Occlusion

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.

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Infarct Volume on Apparent Diffusion Coefficient Maps Correlates with Length of Stay and Outcome after Middle Cerebral Artery Stroke

Cerebrovascular Diseases ◽

10.1159/000068826 ◽

2003 ◽

Vol 15 (3) ◽

pp. 188-191 ◽

Cited By ~ 40

Author(s):

Stefan T. Engelter ◽

James M. Provenzale ◽

Jeffrey R. Petrella ◽

David M. DeLong ◽

Mark J. Alberts

Keyword(s):

Diffusion Coefficient ◽

Length Of Stay ◽

Apparent Diffusion Coefficient ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Infarct Volume ◽

Apparent Diffusion ◽

Apparent Diffusion Coefficient Maps ◽

Middle Cerebral Artery Stroke

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MitoKATP opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00054.2002 ◽

2002 ◽

Vol 283 (3) ◽

pp. H1005-H1011 ◽

Cited By ~ 74

Author(s):

Katsuyoshi Shimizu ◽

Zsombor Lacza ◽

Nishadi Rajapakse ◽

Takashi Horiguchi ◽

James Snipes ◽

...

Keyword(s):

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Ischemia Reperfusion Injury ◽

Neuronal Damage ◽

Infarct Volume ◽

Ischemia Reperfusion ◽

Artery Occlusion ◽

Sham Treatment ◽

Cerebral Artery Occlusion

We investigated effects of diazoxide, a selective opener of mitochondrial ATP-sensitive K+ (mitoKATP) channels, against brain damage after middle cerebral artery occlusion (MCAO) in male Wistar rats. Diazoxide (0.4 or 2 mM in 30 μl saline) or saline (sham) was infused into the right lateral ventricle 15 min before MCAO. Neurological score was improved 24 h later in the animals treated with 2 mM diazoxide (13.8 ± 0.7, n = 13) compared with sham treatment (9.5 ± 0.2, n = 6, P < 0.01). The total percent infarct volume (MCAO vs. contralateral side) of sham treatment animals was 43.6 ± 3.6% ( n = 12). Treatment with 2 mM diazoxide reduced the infarct volume to 20.9 ± 4.8% ( n = 13, P < 0.05). Effects of diazoxide were prominent in the cerebral cortex. The protective effect of diazoxide was completely prevented by the pretreatment with 5-hydroxydecanoate (100 mM in 10 μl saline), a selective blocker of mitoKATP channels ( n = 6). These results indicate that selective opening of the mitoKATP channel has neuroprotective effects against ischemia-reperfusion injury in the rat brain.

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Abstract 11511: Genetic Variation in Retinal Vascular Patterning Predicts Variation in Pial Collateral Extent and Infarct Volume After Middle Cerebral Artery Occlusion

Circulation ◽

10.1161/circ.130.suppl_2.11511 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Pranay Prabhakar ◽

Hua Zhang ◽

De Chen ◽

Stephen Lockett ◽

James E Faber

Keyword(s):

Genetic Variation ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Genetic Background ◽

Infarct Volume ◽

Indirect Evidence ◽

Artery Occlusion ◽

Stroke Severity ◽

Cerebral Artery Occlusion

Introduction: The presence of a native (pre-existing) collateral circulation in tissues lessens injury in stroke and other occlusive diseases. However, differences in genetic background are accompanied by wide variation in the number and diameter (extent) of native collaterals in mice, resulting in large variation in protection. Indirect evidence suggests a similar wide variation also exists in humans. However, methods of measurement in humans are indirect, invasive and not widely available. Hypothesis: We sought to determine if differences in genetic background in mice result in variation in branch-patterning of the retinal circulation, and if these differences predict differences in collateral extent and, in turn, differences in severity of ischemic stroke. Methods: Patterning metrics were obtained for the retinal arterial trees of 10 mouse strains (n=8 per strain) that differ widely in collateral extent in brain and other tissues. We also obtained pial collateral number and diameter, and infarct volume 24h after permanent middle cerebral artery occlusion. Forward- and reverse-stepwise multivariate regression analysis was conducted and model performance assessed using K-fold cross-validation. Results: Twenty-one metrics varied significantly with genetic strain (p<0.01). Ten metrics (eg, vessel caliber, bifurcation angle, lacunarity, optimality, branch length) strongly predicted collateral number and diameter across 7 regression models. The best models closely predicted (p<0.0001) collateral number (K-fold R 2 =0.83-0.98), diameter (0.73-0.88) and infarct volume (0.85-0.87). Conclusions: Differences in retinal tree patterning are specified by genetic background and closely predict genetic variation in pial collateral extent and, in turn, stroke severity. If these findings can be confirmed in humans, and given that genetic variation in cerebral collaterals extends to other tissues at least in mice, a similar “retinal predictor index” could be developed as a biomarker for collateral extent in brain and other tissues. This could aid prediction of the risk-severity of tissue injury in occlusive disease as well as stratification of patients for treatment options and enrollment in clinical studies.

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Melatonin and calpeptin synergistically protect against post-reperfusion injury in a rat middle cerebral artery occlusion stroke model

Melatonin Research ◽

10.32794/mr112500114 ◽

2021 ◽

Vol 4 (4) ◽

pp. 592-612

Author(s):

Ye Feng ◽

Qian Xu ◽

Raymond Tak Fai Cheung

Keyword(s):

Cerebral Ischemia ◽

Middle Cerebral Artery ◽

Reperfusion Injury ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Neurological Deficit ◽

Infarct Volume ◽

Artery Occlusion ◽

Stroke Model ◽

Cerebral Artery Occlusion

Cerebral ischemia induces oxidative injury and increases the intracellular calcium ion concentration to activate several calcium-dependent proteases such as calpains. Calpain activation leads to various necrotic and apoptotic processes. Calpeptin is a potent, cell-permeable calpain inhibitor. As a strong antioxidant and free radical scavenger, melatonin shows beneficial effect in rodent models of focal cerebral ischemia when given prior to ischemia or reperfusion. This study was focused on the neuroprotective effects of melatonin and/or calpeptin given after onset of reperfusion. For this purpose, right-sided middle cerebral artery occlusion (MCAO) for 90 minutes followed by 24 or 72 hours of reperfusion was performed in male Sprague Dawley rats, then, melatonin 50 or 150 µg/kg, calpeptin 10, 15 or 50 µg/kg or a combination of melatonin 50 µg/kg plus calpeptin 15 or 50 µg/kg were injected via an intracerebroventricular route at 15 minutes after onset of reperfusion. Melatonin or calpeptin tended to reduce the relative infarct volume and significantly decreased the neurological deficit at 24 hours. The combination achieved a greater protection than each of them alone. Melatonin, calpeptin or the combination all decreased Fluoro-Jade B (FJB)+ degenerative neurons and cleaved/total caspase-3 ratio at 24 hours. These treatments did not significantly impact the density of surviving neurons and ED-1+ macrophage/activated microglia. At the 72-hour-reperfusion, melatonin or the combination decreased the relative infarct volume and neurological deficit. Nevertheless, only the combination reduced FJB+ degenerating neurons at 72 hours. In conclusion, a combination of melatonin and calpeptin exerted synergistic protection against post-reperfusion injury in a rat MCAO stroke model.

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Demonstration of therapeutic window of Cerebrolysin in embolic stroke: A prospective, randomized, blinded, and placebo-controlled study

International Journal of Stroke ◽

10.1177/1747493017702665 ◽

2017 ◽

Vol 12 (6) ◽

pp. 628-635 ◽

Cited By ~ 5

Author(s):

Li Zhang ◽

Michael Chopp ◽

Mei Lu ◽

Talan Zhang ◽

Chao Li ◽

...

Keyword(s):

Confidence Interval ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Infarct Volume ◽

Artery Occlusion ◽

Mean Difference ◽

Embolic Stroke ◽

Therapeutic Window ◽

Cerebral Artery Occlusion

Background and aims In an effort to characterize the effects of Cerebrolysin for treatment of stroke that are essential for successful clinical translation, we have demonstrated that Cerebrolysin dose dependently enhanced neurological functional recovery in experimental stroke. Here, we conduct a prospective, randomized, placebo-controlled, blinded study to examine the therapeutic window of Cerebrolysin treatment of rats subjected to embolic stroke. Methods Male Wistar rats age 3–4 months (n = 100) were subjected to embolic middle cerebral artery occlusion. Animals were randomized to receive saline or Cerebrolysin daily for 10 consecutive days starting 4, 24, 48, and 72 h after middle cerebral artery occlusion. Neurological outcome was measured weekly with a battery of behavioral tests (adhesive removal test, modified neurological severity score (mNSS), and foot-fault test). Global test was employed to assess Cerebrolysin effect on neurological recovery with estimation of mean difference between Cerebrolysin and control-treated groups and its 95% confidence interval in the intent-to-treat population, where a negative value of the mean difference and 95% confidence interval < 0 indicated a significant treatment effect. All rats were sacrificed 28 days after middle cerebral artery occlusion and infarct volume was measured. Results Cerebrolysin treatment initiated within 48 h after middle cerebral artery occlusion onset significantly improved functional outcome; mean differences and 95% confidence interval were −11.6 (−17.7, −5.4) at 4 h, −7.1 (−13.5, −0.8) at 24 h, −8.4 (−14.2, −8.6) at 48 h, and −4.9 (−11.4, 1.5) at 72 h. There were no differences on infarct volume and mortality rate among groups. Conclusions With a clinically relevant rigorous experimental design, our data demonstrate that Cerebrolysin treatment effectively improves stroke recovery when administered up to 48 h after middle cerebral artery occlusion.

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