Cerebral microcirculatory alterations and the no-reflow phenomenon in vivo after experimental pediatric cardiac arrest

Li, Lingjue; Poloyac, Samuel M.; Watkins, Simon C.; Croix, Claudette M. St.; Alexander, Henry; Gibson, Gregory A.; Loughran, Patricia; Kirisci, Levent; Clark, Robert S. B.; Kochanek, Patrick M.; Vazquez, Alberto L.; Manole, Mioara D.

doi:10.1177/0271678x17744717

Cited by 20 publications

(18 citation statements)

References 37 publications

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“…Studies using intravital microscopy indicate that the pial and capillary vascular network regulate 75% of the changes in cerebral blood flow via effects on vascular resistance and mean transit time. 99,100 Normally, pericytes support astrocyte polarity and limit endothelial transcytosis required for regulating solute entry to the brain. 101 With physiological stimulation, glutamate, prostaglandin E2, and nitric oxide induce pericyte relaxation allowing for increased blood flow.…”

Section: The ‘No-reflow’ Phenomenonmentioning

confidence: 99%

The post-cardiac arrest syndrome: A case for lung–brain coupling and opportunities for neuroprotection

Mai

Miller-Rhodes

Knowlden

et al. 2019

J Cereb Blood Flow Metab

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Systemic inflammation and multi-organ failure represent hallmarks of the post-cardiac arrest syndrome (PCAS) and predict severe neurological injury and often fatal outcomes. Current interventions for cardiac arrest focus on the reversal of precipitating cardiac pathologies and the implementation of supportive measures with the goal of limiting damage to at-risk tissue. Despite the widespread use of targeted temperature management, there remain no proven approaches to manage reperfusion injury in the period following the return of spontaneous circulation. Recent evidence has implicated the lung as a moderator of systemic inflammation following remote somatic injury in part through effects on innate immune priming. In this review, we explore concepts related to lung-dependent innate immune priming and its potential role in PCAS. Specifically, we propose and investigate the conceptual model of lung–brain coupling drawing from the broader literature connecting tissue damage and acute lung injury with cerebral reperfusion injury. Subsequently, we consider the role that interventions designed to short-circuit lung-dependent immune priming might play in improving patient outcomes following cardiac arrest and possibly other acute neurological injuries.

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Section: The ‘No-reflow’ Phenomenonmentioning

confidence: 99%

The post-cardiac arrest syndrome: A case for lung–brain coupling and opportunities for neuroprotection

Mai

Miller-Rhodes

Knowlden

et al. 2019

J Cereb Blood Flow Metab

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“…Hence, even though we did not observe signi cantly different absolute CBV and CBF between survival and non-survival groups, we did nd an increased CBV and CBF during the early phase (20 min to 12 h from ROSC) in OHCA survivors compared to the healthy brain. This cerebral hyperaemia can be caused by an intravascular stasis (known as the nore ow phenomenon) [27] and by an imbalance between vasodilators and vasoconstrictors (e.g., nitrogen oxide and endothelin-1, respectively) [28].…”

Section: Discussionmentioning

confidence: 99%

Global Impairment of Cerebral Perfusion Measured using Dynamic Susceptibility Contrast Perfusion-Weighted Imaging in Out-of-Hospital Cardiac Arrest Survivors: A Prospectively Preliminary Study

Kang

Park

You

et al. 2020

Preprint

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Background: Dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI) is useful for measuring cerebral perfusion (CP). This study aimed to assess global impairment and the prognostic performance of CP parameters measured by DSC-PWI in out-of-hospital cardiac arrest (OHCA) survivors.Methods: This is a single-centre, prospective observational study. OHCA survivors who underwent DSC-PWI within 6 h after restoration of spontaneous circulation were enrolled. CP parameters (cerebral blood volume [CBV], cerebral blood flow [CBF], mean transit time [MTT], time to peak [TTP], and time to the maximum of the residue function [Tmax]) were quantified by normalisation + leakage correction (LC) or by arterial input function (AIF) + LC. The primary outcome was survival to discharge; subjects who died due to withdrawal of life-sustaining therapy or who were diagnosed with brain death (BD) were included in non-survival. The secondary outcome was 6-months neurological outcome. CP parameters were compared across groups, and receiver operating characteristic (ROC) curves were constructed to assess prognostic performances.Results: Thirty-one subjects (male, 20; 64.5%) participated. Relative CBV (rCBV) and CBF (rCBF) quantified by normalisation + LC were significantly higher in the non-survival group (p=0.02 and p=0.03, respectively). The area under the ROC curves (AUROCs) and 100% specific sensitivities for non-survival were 0.75/31.3% and 0.73/25.0%, respectively. MTT and Tmax quantified by AIF + LC were significantly higher in non-survival (p=0.01 and p=0.01, respectively). Their AUROCs and 100% specific sensitivities were 0.77/56.3% and 0.76/43.8%, respectively. rCBV and rCBF quantified by normalisation + LC were significantly higher in the poor neurological outcome group (p<0.01 and p=0.02, respectively). The AUROCs and 100% specific sensitivities for poor neurological outcome were 0.81/23.8% and 0.77/19.1%, respectively. Tmax quantified by AIF + LC was significantly higher in poor neurological outcome (p=0.04). Its AUROC and 100% specific sensitivity were 0.74/33.3%.Conclusion: Hyperaemia and delayed CP were present in the non-survival and poor neurological outcome groups. MTT quantified by AIF + LC could be the most powerful parameter for predicting mortality or BD in OHCA survivors at an early stage of post cardiac arrest care. AIF may be more appropriate as quantifying method for CP in OHCA survivors than normalisation.

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“…Animal preparation for in vivo microscopy was performed using a method adapted from a recent study of the rat cortical microvasculature (Li et al, 2017), with addition of an i.c. catheter for administration of EBA and aCSF, and monitoring of ICP (Figure 1A).…”

Section: Methodsmentioning

confidence: 99%

Quantitative and qualitative assessment of glymphatic flux using Evans blue albumin

Wolf

Chen

Simon

et al. 2019

Journal of Neuroscience Methods

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Background: The glymphatic system is a proposed pathway for clearance of proteins and macromolecules from brain, and disrupted glymphatic flux is implicated in neurological disease. We capitalized on colorimetric, fluorescent, and protein-binding properties of Evans blue to evaluate glymphatic flux. New method: Twenty-five μL of 1% Evans blue-labeled albumin (EBA) in artificial cerebrospinal fluid (aCSF) was injected into the intracisternal space of anesthetized postnatal day 17 rats. Serum was collected at various time points after injection (n=37) and EBA was measured spectrophotometrically. In separate rats (n = 3), a cranial window was placed over the parietal cortex and EBA transit was evaluated using in vivo multiphoton microscopy. Separate rats (n = 6) were processed for immunohistochemistry to examine localization of EBA. In some rats, intracranial pressure (ICP) was increased via intracisternal injection of aCSF. Results: EBA was detected in serum as early as 30 min, was maximal at 4 h, and was undetectable at 72 h after intracisternal injection. Using intra-vital microscopy and immunohistochemistry EBA could be tracked from CSF to perivascular locations. Consistent with removal via glymphatic flux, increasing ICP to 40 mmHg accelerated transit of EBA from CSF to blood. Comparison with existing methods: Transit of EBA from CSF to serum could be quantified spectrophotometrically without radioactive labeling. Glymphatic flux could also be qualitatively evaluated using EBA fluorescence. Conclusion: We present a novel technique for simultaneous quantitative and qualitative evaluation of glymphatic flux in rats.

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Cerebral microcirculatory alterations and the no-reflow phenomenon in vivo after experimental pediatric cardiac arrest

Cited by 20 publications

References 37 publications

The post-cardiac arrest syndrome: A case for lung–brain coupling and opportunities for neuroprotection

The post-cardiac arrest syndrome: A case for lung–brain coupling and opportunities for neuroprotection

Global Impairment of Cerebral Perfusion Measured using Dynamic Susceptibility Contrast Perfusion-Weighted Imaging in Out-of-Hospital Cardiac Arrest Survivors: A Prospectively Preliminary Study

Quantitative and qualitative assessment of glymphatic flux using Evans blue albumin

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