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Targeted ischemic stroke induction and mesoscopic imaging assessment of blood flow and ischemic depolarization in awake mice.

ABSTRACT: Despite advances in experimental stroke models, confounding factors such as anesthetics used during stroke induction remain. Furthermore, imaging of blood flow during stroke is not routinely done. We take advantage of in vivo bihemispheric transcranial windows for longitudinal mesoscopic imaging of cortical function to establish a protocol for focal ischemic stroke induction in target brain regions using photothrombosis in awake head-fixed mice. Our protocol does not require any surgical steps at the time of stroke induction or anesthetics during either head fixation or photoactivation. In addition, we performed laser speckle contrast imaging and wide-field calcium imaging to reveal the effect of cortical spreading ischemic depolarization after stroke in both anesthetized and awake animals over a spatial scale encompassing both hemispheres. With our combined approach, we observed ischemic depolarizing waves (3 to [Formula: see text]) propagating across the cortex 1 to 5 min after stroke induction in genetically encoded calcium indicator mice. Measures of blood flow by laser speckle were correlated with neurological impairment and lesion volume, suggesting a metric for reducing experimental variability. The ability to follow brain dynamics immediately after stroke as well as during recovery may provide a valuable guide to develop activity-dependent therapeutic interventions to be performed shortly after stroke induction.

SUBMITTER: Balbi M

PROVIDER: S-EPMC5512458 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Targeted ischemic stroke induction and mesoscopic imaging assessment of blood flow and ischemic depolarization in awake mice.

Balbi Matilde M Vanni Matthieu P MP Silasi Gergely G Sekino Yuki Y Bolanos Luis L LeDue Jeffrey M JM Murphy Timothy H TH

Neurophotonics 20170714 3

Despite advances in experimental stroke models, confounding factors such as anesthetics used during stroke induction remain. Furthermore, imaging of blood flow during stroke is not routinely done. We take advantage of <i>in vivo</i> bihemispheric transcranial windows for longitudinal mesoscopic imaging of cortical function to establish a protocol for focal ischemic stroke induction in target brain regions using photothrombosis in awake head-fixed mice. Our protocol does not require any surgical ...[more]

PMID: 28721356

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Project description:Background and purposeCollateral blood flow is an important prognostic marker in the acute stroke situation but approaches for assessment vary widely. Our aim was to compare strategies of collateral blood flow assessment in dynamic and conventional CTA in their ability to predict the follow-up infarction volume.Materials and methodsWe retrospectively included all patients with an M1 occlusion from an existing cohort of 1912 consecutive patients who underwent initial multimodal stroke CT and follow-up MR imaging or nonenhanced CT. Collateralization was assessed in both conventional CT angiography and dynamic CT angiography by using 3 different collateral grading scores and segmentation of the volume of hypoattenuation. Arterial, arteriovenous, and venous phases were reconstructed for dynamic CT angiography, and all collateral scores and the volume of hypoattenuation were individually assessed for all phases. Different grading systems were compared by using the Bayesian information criterion calculated for multivariate regression analyses (Bayesian information criterion difference = 2-6, "positive"; Bayesian information criterion difference = 6-10, "strong"; Bayesian information criterion difference = >10, "very strong").ResultsOne hundred thirty-six patients (mean age, 70.4 years; male sex, 41.2%) were included. In the multivariate analysis, models containing the volume of hypoattenuation showed a significantly better model fit than models containing any of the 3 collateral grading scores in conventional CT angiography (Bayesian information criterion difference = >10) and dynamic CT angiography (Bayesian information criterion difference = >10). All grading systems showed the best model fit in the arteriovenous phase. For the volume of hypoattenuation, model fit was significantly higher for models containing the volume of hypoattenuation as assessed in the arteriovenous phase of dynamic CT angiography compared with the venous phase (Bayesian information criterion difference = 6.2) and the arterial phase of dynamic CT angiography (Bayesian information criterion difference = >10) and in comparison with conventional CT angiography (Bayesian information criterion difference = >10).ConclusionsThe use of dynamic CT angiography within the arteriovenous phase by using quantification of the volume of hypoattenuation is the superior technique for assessment of collateralization among the tested approaches.

Dataset Information

Targeted ischemic stroke induction and mesoscopic imaging assessment of blood flow and ischemic depolarization in awake mice.

Publications

Targeted ischemic stroke induction and mesoscopic imaging assessment of blood flow and ischemic depolarization in awake mice.

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