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Early Thalamocortical Reperfusion Leads to Neurologic Recovery in a Rodent Cardiac Arrest Model

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Abstract

Background

Cerebral blood flow (CBF) plays an important role in neurological recovery after cardiac arrest (CA) resuscitation. However, the variations of CBF recovery in distinct brain regions and its correlation with neurologic recovery after return of spontaneous circulation (ROSC) have not been characterized. This study aimed to investigate the characteristics of regional cerebral reperfusion following resuscitation in predicting neurological recovery.

Methods

Twelve adult male Wistar rats were studied, ten resuscitated from 7-min asphyxial CA and two uninjured rats, which were designated as healthy controls (HCs). Dynamic changes in CBF in the cerebral cortex, hippocampus, thalamus, brainstem, and cerebellum were assessed by pseudocontinuous arterial spin labeling magnetic resonance imaging, starting at 60 min after ROSC to 156 min (or time to spontaneous arousal). Neurologic outcomes were evaluated by the neurologic deficit scale at 24 h post-ROSC in a blinded manner. Correlations between regional CBF (rCBF) and neurological recovery were undertaken.

Results

All post-CA animals were found to be nonresponsive during the 60–156 min post ROSC, with reductions in rCBF by 24–42% compared with HC. Analyses of rCBF during the post-ROSC time window from 60 to 156 min showed the rCBF recovery of hippocampus and thalamus were positively associated with better neurological outcomes (rs = 0.82, p = 0.004 and rs = 0.73, p < 0.001, respectively). During 96 min before arousal, thalamic and cortical rCBF exhibited positive correlations with neurological recovery (rs = 0.80, p < 0.001 and rs = 0.65, p < 0.001, respectively); for predicting a favorable neurological outcome, the thalamic rCBF threshold was above 50.84 ml/100 g/min (34% of HC) (area under the curve of 0.96), whereas the cortical rCBF threshold was above 60.43 ml/100 g/min (38% of HC) (area under the curve of 0.88).

Conclusions

Early magnetic resonance imaging analyses showed early rCBF recovery in thalamus, hippocampus, and cortex post ROSC was positively correlated with neurological outcomes at 24 h. Our findings suggest new translational insights into the regional reperfusion and the time window that may be critical in neurological recovery and warrant further validation.

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Funding

This work was supported by National Institutes of Health grants R01 HL071568-15, R01 HL139158-01A1, R01 AG064792, and R21 AG058413.

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Author notes

  1. Yu Guo and Sung-Min Cho contributed equally as co-first authors.

Authors and Affiliations

  1. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Yu Guo, Qihong Wang, Hiren R. Modi, Hanzhang Lu & Nitish V. Thakor

  2. Departments of Neurology, Anesthesiology, Critical Care Medicine and Neurosurgery, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Phipps 455, Baltimore, MD, 21287, USA

    Sung-Min Cho & Romergryko G. Geocadin

  3. Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Zhiliang Wei & Hanzhang Lu

  4. Departments of Neurology, Division of Neuroimmunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Payam Gharibani

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  1. Yu Guo
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Contributions

RGG: supervised the project, provided research idea, reviewed the article, and served as the co-principal investigator. NVT: supervised the project, reviewed the article, and served as the co-principal investigator. YG: conducted data analyses and prepared the article. SMC: provided research idea and reviewed the article. ZW, QW, and HM: conducted animal experiments and data collection. PG: consulted and reviewed/edited the article. HL: supervised the magnetic resonance imaging study. All authors contributed to article revisions and approved the final manuscript.

Corresponding author

Correspondence to Romergryko G. Geocadin.

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Guo, Y., Cho, SM., Wei, Z. et al. Early Thalamocortical Reperfusion Leads to Neurologic Recovery in a Rodent Cardiac Arrest Model. Neurocrit Care 37, 60–72 (2022). https://doi.org/10.1007/s12028-021-01432-9

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  • DOI: https://doi.org/10.1007/s12028-021-01432-9

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