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Published in: Translational Stroke Research 4/2020

Open Access 01-08-2020 | Magnetic Resonance Imaging | Original Article

Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model

Authors: Samantha E. Spellicy, Erin E. Kaiser, Michael M. Bowler, Brian J. Jurgielewicz, Robin L. Webb, Franklin D. West, Steven L. Stice

Published in: Translational Stroke Research | Issue 4/2020

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Abstract

Magnetic resonance imaging (MRI) is a clinically relevant non-invasive imaging tool commonly utilized to assess stroke progression in real time. This study investigated the utility of MRI as a predictive measure of clinical and functional outcomes when a stroke intervention is withheld or provided, in order to identify biomarkers for stroke functional outcome under these conditions. Fifteen MRI and ninety functional parameters were measured in a middle cerebral artery occlusion (MCAO) porcine ischemic stroke model. Multiparametric analysis of correlations between MRI measurements and functional outcome was conducted. Acute axial and coronal midline shift (MLS) at 24 h post-stroke were associated with decreased survival and recovery measured by modified Rankin scale (mRS) and were significantly correlated with 52 measured acute (day 1 post) and chronic (day 84 post) gait and behavior impairments in non-treated stroked animals. These results suggest that MLS may be an important non-invasive biomarker that can be used to predict patient outcomes and prognosis as well as guide therapeutic intervention and rehabilitation in non-treated animals and potentially human patients that do not receive interventional treatments. Neural stem cell–derived extracellular vesicle (NSC EV) was a disruptive therapy because NSC EV administration post-stroke disrupted MLS correlations observed in non-treated stroked animals. MLS was not associated with survival and functional outcomes in NSC EV–treated animals. In contrast to untreated animals, NSC EVs improved stroked animal outcomes regardless of MLS severity.
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Literature
11.
go back to reference Sorby-Adams AJ, Vink R, Turner RJ. Large animal models of stroke and traumatic brain injury as translational tools. Am J Physiol. 2018;315:R165–R90 Sorby-Adams AJ, Vink R, Turner RJ. Large animal models of stroke and traumatic brain injury as translational tools. Am J Physiol. 2018;315:R165–R90
25.
go back to reference Deng L, Peng Q, Wang H, Pan J, Zhou Y, Pan K, et al. Intrathecal injection of allogenic bone marrow-derived mesenchymal stromal cells in treatment of patients with severe ischemic stroke: study protocol for a randomized controlled observer-blinded trial. Transl Stroke Res. 2019;10(2):170–7. https://doi.org/10.1007/s12975-018-0634-y.CrossRefPubMed Deng L, Peng Q, Wang H, Pan J, Zhou Y, Pan K, et al. Intrathecal injection of allogenic bone marrow-derived mesenchymal stromal cells in treatment of patients with severe ischemic stroke: study protocol for a randomized controlled observer-blinded trial. Transl Stroke Res. 2019;10(2):170–7. https://​doi.​org/​10.​1007/​s12975-018-0634-y.CrossRefPubMed
33.
35.
go back to reference Platt SR, Holmes SP, Howerth EW, Duberstein KJJ, Dove CR, Kinder HA, et al. Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model. Exp Transl Stroke Med. 2014;6:5.CrossRef Platt SR, Holmes SP, Howerth EW, Duberstein KJJ, Dove CR, Kinder HA, et al. Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model. Exp Transl Stroke Med. 2014;6:5.CrossRef
42.
go back to reference Lewis M, Olby N, Early P, Mariani C, Muñana K, Seiler G, et al. Clinical and diagnostic imaging features of brain herniation in dogs and cats. J Vet Intern Med. 2016;30(5):1672–80.CrossRef Lewis M, Olby N, Early P, Mariani C, Muñana K, Seiler G, et al. Clinical and diagnostic imaging features of brain herniation in dogs and cats. J Vet Intern Med. 2016;30(5):1672–80.CrossRef
44.
go back to reference Bonita R, Beaglehole R. Recovery of motor function after stroke. Stroke. 1988;19(12):1497–500.CrossRef Bonita R, Beaglehole R. Recovery of motor function after stroke. Stroke. 1988;19(12):1497–500.CrossRef
69.
go back to reference Ramiro J, Dhar R, Feen E, Kumar A. Improvement in midline shift is associated with survival after decompressive hemicraniectomy in large hemispheric infarctions (P2.287). 2015;84:P2.287. Ramiro J, Dhar R, Feen E, Kumar A. Improvement in midline shift is associated with survival after decompressive hemicraniectomy in large hemispheric infarctions (P2.287). 2015;84:P2.287.
71.
go back to reference Jeon SB, Kwon SU, Park JC, Lee DH, Yun SC, Kim YJ, et al. Reduction of midline shift following decompressive hemicraniectomy for malignant middle cerebral artery infarction. J Stroke. 2016;18(3):328–36.CrossRef Jeon SB, Kwon SU, Park JC, Lee DH, Yun SC, Kim YJ, et al. Reduction of midline shift following decompressive hemicraniectomy for malignant middle cerebral artery infarction. J Stroke. 2016;18(3):328–36.CrossRef
72.
go back to reference Woo CW, Kwon JI, Kim KW, Kim JK, Jeon SB, Jung SC, et al. The administration of hydrogen sulphide prior to ischemic reperfusion has neuroprotective effects in an acute stroke model. PLoS One. 2017;12(11):e0187910.CrossRef Woo CW, Kwon JI, Kim KW, Kim JK, Jeon SB, Jung SC, et al. The administration of hydrogen sulphide prior to ischemic reperfusion has neuroprotective effects in an acute stroke model. PLoS One. 2017;12(11):e0187910.CrossRef
74.
go back to reference Morrison SF, Nakamura K. Central neural pathways for thermoregulation. Front Biosci. 2011;16:74–104.CrossRef Morrison SF, Nakamura K. Central neural pathways for thermoregulation. Front Biosci. 2011;16:74–104.CrossRef
Metadata
Title
Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model
Authors
Samantha E. Spellicy
Erin E. Kaiser
Michael M. Bowler
Brian J. Jurgielewicz
Robin L. Webb
Franklin D. West
Steven L. Stice
Publication date
01-08-2020
Publisher
Springer US
Published in
Translational Stroke Research / Issue 4/2020
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-019-00753-4

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