Interaction of age with the ischaemic penumbra, leptomeningeal collateral circulation and haemodynamic variables in acute stroke: a pilot study

Agarwal, Smriti; Scoffings, Daniel; Jones, P. Simon; Marrapu, S. Tulasi; Barry, Patrick; O’Brien, Eoin; Baron, Jean‐Claude; Warburton, Elizabeth A.

doi:10.1136/jnnp-2012-303258

Cited by 32 publications

(25 citation statements)

References 38 publications

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“…The discrepancies may be due to the difference in animal strains, animal sexes, or ischemic models used in the studies. Several clinical studies 7, 26 demonstrated age negatively correlated with the size of either the ischemic lesion or the penumbral area in stroke patients, which is consistent with the results from our studies. Despite discrepancies in histological outcomes, there is agreement in most preclinical and clinical studies that functional (behavioral) stroke outcomes are worse in aged cohorts 2, 6, 22, 27 .…”

Section: Discussionsupporting

confidence: 92%

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Perfusion of Ischemic Brain in Young and Aged Animals

Manwani

Friedler

Verma

et al. 2014

Stroke

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Background and Purpose Aging is an important determinant of ischemic stroke outcomes. Both clinical and experimental stroke studies have shown that aging negatively correlates with infarct volumes but is associated with worsened functional recovery after stroke. This may correspond to a differing cellular and molecular response to stroke in the aged vs. young brain. It was hypothesized in this study that the smaller injury seen in the aged ischemic brain is due to structural differences in microvasculature with aging or differences in intra-ischemic tissue perfusion. Methods Both young and aged C57BL6 mice were subject to middle cerebral artery occlusion (MCAO) modeling. Laser Speckle Flowmetry (LSF) was utilized to study the functional dynamics of cerebral perfusion, and FITC-dextran staining was performed to examine the structural change in microvasculature. In separate cohorts, Cresyl violet (CV) staining and immunohistochemistry with CD31 and IgG antibodies were applied to further assess the microvascular density and blood brain barrier breakdown after stroke. Results No difference in cerebral blood flow was seen at the baseline, intra-ischemically and post-reperfusion in young vs. aged mice. FITC-dextran and CD31 staining did not show significant differences in the microvascular density between young and aged ischemic brains. More extravasation of IgG through the BBB was found in the young vs. aged cohort at both 24 and 72 hours after stroke. Conclusions Cerebrovascular dynamics and perfusion are not responsible for the different stroke phenotypes seen in the young vs. aged animals, which may be more related to different levels of BBB breakdown.

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Section: Discussionsupporting

confidence: 92%

“…We have shown that aged male mice have smaller infarct volumes but worse functional recovery when compared with young mice 4–6 , which is consistent with clinical data 7 . However, the underlying mechanism for this discrepancy in histological and functional outcome is unclear.…”

Section: Introductionsupporting

confidence: 90%

Perfusion of Ischemic Brain in Young and Aged Animals

Manwani

Friedler

Verma

et al. 2014

Stroke

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“…Therefore, impairments in function are likely regardless of cortical health, diminishing the likelihood of strong volume-function correlations with regards to cortical and total volumes acutely [28]. This is particularly true with regards to the aged rodent model utilized herein as cortical volumes are typically larger in this model due to reduce collateralization with age and therefore, increased tissue susceptibility to ischemia [29]. There is less discrepancy in collateral flow with regards to the striatum between young and aged rodents, resulting in more uniformity when considering striatal infarct volumes.…”

Section: Discussionmentioning

confidence: 99%

The role for infarct volume as a surrogate measure of functional outcome following ischemic stroke

Turner¹,

DiPasquale²,

Logsdon³

et al. 2016

J Syst Integr Neurosci

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The failed translation of proposed therapeutic agents for ischemic stroke from preclinical to clinical studies has led to increased scrutiny of preclinical studies, namely the model and outcome measures utilized. Preclinical studies routinely use infarct volume as an experimental endpoint or measure in studies employing young-adult, healthy male animals despite the fact that clinically, ischemic stroke is a disease of the elderly and improvements in functional outcome from pre- to post-intervention remains the most widely utilized assessment. The validity of infarct volume as a surrogate measure for functional outcome remains unclear in clinical studies as well as preclinical studies, particularly those utilizing a more clinically relevant aged thromboembolic model. In this work, we will address the relationship between acute and chronic functional outcome and infarct volume using a variety of functional assessments ranging from more simplistic, subjective measurements such as the modified Neurologic Severity Score (mNSS), to more complex, objective measurements such as grip strength and inclined plane.

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“…There are examples of attempts to examine the factors that predict independent survival5 or recovery of language function in those with aphasia,6 as well as outcomes in a number of stroke subtypes or treatment scenarios. There are studies examining the effect of important variables such as age,7 cognitive impairment4 and infection8 on outcomes. These attempts to predict outcomes based on key variables are important for patients, carers and clinicians in defining appropriate care but also for stratification of patients in treatment studies.…”

mentioning

confidence: 99%

Stroke: mechanisms, stratification and implementation

Ward

2013

Journal of Neurology, Neurosurgery & Psychiatry

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Interaction of age with the ischaemic penumbra, leptomeningeal collateral circulation and haemodynamic variables in acute stroke: a pilot study

Cited by 32 publications

References 38 publications

Perfusion of Ischemic Brain in Young and Aged Animals

Perfusion of Ischemic Brain in Young and Aged Animals

The role for infarct volume as a surrogate measure of functional outcome following ischemic stroke

Stroke: mechanisms, stratification and implementation

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