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Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Research Article

Impact of Collateral Status on Neuroprotective Effect of Cyclosporine A in Acute Ischemic Stroke

Author(s): Norbert Nighoghossian*, Lucie Cornut, Camille Amaz, Omer Eker, Nathan Mewton, Roxana Ameli, Lise Prune Berner, Tae Hee Cho, Michel Ovize and Yves Berthezene

Volume 16, Issue 2, 2019

Page: [173 - 177] Pages: 5

DOI: 10.2174/1567202616666190618094014

Price: $65

Abstract

Background: Neuroprotection for acute ischemic stroke remains an elusive goal. Intracranial collaterals may favor neuroprotective drugs delivery at the acute stage of ischemic stroke. A recent phase 2 study showed that cyclosporine A (CsA) reduced ischemic damage in patients with a proximal occlusion who experienced effective recanalization. Collateral flow may improve this benefit.

Materials & Methods: Collateral supply was assessed using dynamic susceptibility contrast MRI in 47 patients among the 110 patients from the original study and were graded in two groups: good collaterals and poor collaterals. Patients with good collaterals had significantly smaller initial infarct in both CsA group (p = 0.003) and controls (p = 0.016). Similarly, the final lesion volume was significantly lower in patients with good collaterals in both groups.

Results: In patients with either good or poor collaterals CsA showed no additional benefit on ischemic lesion progression and final infarct size at day 30.

Conclusion: We failed to demonstrate any significant additional benefit of CsA in patients with good collateral circulation.

Keywords: Acute ischemic stroke, collateral flow, MRI, cyclosporine, reperfusion, neuroprotection.

[1]
Nighoghossian N, Berthezène Y, Mechtouff L, et al. Cyclosporine in acute ischemic stroke. Neurology 2015; 84(22): 2216-23. [http://dx.doi.org/10.1212/WNL.0000000000001639]. [PMID: 25948727].
[2]
Amaro S, Laredo C, Renú A, et al. Uric acid therapy prevents early ischemic stroke progression: A tertiary analysis of the URICO-ICTUS trial (Efficacy study of combined treatment with uric acid and r-tPA in acute ischemic stroke). Stroke 2016; 47(11): 2874-6. [http://dx.doi.org/10.1161/STROKEAHA.116.014672]. [PMID: 27758945].
[3]
Kim SJ, Son JP, Ryoo S, et al. A novel magnetic resonance imaging approach to collateral flow imaging in ischemic stroke. Ann Neurol 2014; 76(3): 356-69. [http://dx.doi.org/10.1002/ana.24211]. [PMID: 24985162].
[4]
Leng X, Lan L, Liu L, Leung TW, Wong KS. Good collateral circulation predicts favorable outcomes in intravenous thrombolysis: a systematic review and meta-analysis. Eur J Neurol 2016; 23(12): 1738-49. [http://dx.doi.org/10.1111/ene.13111]. [PMID: 27478977].
[5]
Liebeskind DS, Tomsick TA, Foster LD, et al. Collaterals at angiography and outcomes in the interventional management of stroke (IMS) III trial. Stroke 2014; 45(3): 759-64. [http://dx.doi.org/10.1161/STROKEAHA.113.004072]. [PMID: 24473178].
[6]
Liu J, Wang Y, Akamatsu Y, et al. Vascular remodeling after ischemic stroke: mechanisms and therapeutic potentials. Prog Neurobiol 2014; 115: 138-56. [http://dx.doi.org/10.1016/j.pneurobio.2013.11.004]. [PMID: 24291532].
[7]
Ginsberg MD. Expanding the concept of neuroprotection for acute ischemic stroke: The pivotal roles of reperfusion and the collateral circulation. Prog Neurobiol 2016; 145-146: 46-77. [http://dx.doi.org/10.1016/j.pneurobio.2016.09.002]. [PMID: 27637159].
[8]
Zhao Z-Q, Corvera JS, Halkos ME. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: Comparison with ischemic preconditioning. Am J Physiol-Heart Circ Physiol 285: H579-88.2003.
[9]
Schinzel AC, Takeuchi O, Huang Z, et al. Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia. Proc Natl Acad Sci USA 2005; 102(34): 12005-10. [http://dx.doi.org/10.1073/pnas.0505294102]. [PMID: 16103352].
[10]
Leger P-L, De Paulis D, Branco S, et al. Evaluation of cyclosporine A in a stroke model in the immature rat brain. Exp Neurol 2011; 230(1): 58-66. [http://dx.doi.org/10.1016/j.expneurol.2010.06.009]. [PMID: 20599982].
[11]
Matsumoto S, Murozono M, Kanazawa M, Nara T, Ozawa T, Watanabe Y. Edaravone and cyclosporine A as neuroprotective agents for acute ischemic stroke. Acute Med Surg 2018; 5(3): 213-21. [http://dx.doi.org/10.1002/ams2.343]. [PMID: 29988669].
[12]
Wu KJ, Yu SJ, Chiang CW, et al. Neuroprotective action of human Wharton’s Jelly-Derived mesenchymal stromal cell transplants in a rodent model of stroke. Cell Transplant 2018; •••963689718802754 [http://dx.doi.org/10.1177/0963689718802754]. [PMID: 30284460].
[13]
Ong E, Mewton N, Bouvier J, et al. Effect of cyclosporine on lesion growth and infarct size within the white and gray matter. Front Neurol 2017. [http://dx.doi.org/10.3389/fneur.2017.00151].

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