Stroke neuroprotection revisited: Intra-arterial verapamil is profoundly neuroprotective in experimental acute ischemic stroke

Michael E. Maniskas, Jill M. Roberts, Ishi Aron, Justin F. Fraser, Gregory J. Bix

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

While clinical trials have now solidified the role of thrombectomy in emergent large vessel occlusive stroke, additional therapies are needed to optimize patient outcome. Using our previously described experimental ischemic stroke model for evaluating adjunctive intra-arterial drug therapy after vessel recanalization, we studied the potential neuroprotective effects of verapamil. A calcium channel blocker, verapamil is often infused intra-arterially by neurointerventionalists to treat cerebral vasospasm. Such a direct route of administration allows for both focused targeting of stroke-impacted brain tissue and minimizes potential systemic side effects. Intra-arterial administration of verapamil at a flow rate of 2.5 μl/min and injection volume of 10 μl immediately after middle cerebral artery recanalization in C57/Bl6 mice was shown to be profoundly neuroprotective as compared to intra-arterial vehicle-treated stroke controls. Specifically, we noted a significant (P ≤ 0.05) decrease in infarct volume, astrogliosis, and cellular apoptosis as well as a significant increase in neuronal survival and functional outcome over seven days. Furthermore, intra-arterial administration of verapamil was well tolerated with no hemorrhage, systemic side effects, or increased mortality. Thus, verapamil administered intra-arterially immediately following recanalization in experimental ischemic stroke is both safe and neuroprotective and merits further study as a potential therapeutic adjunct to thrombectomy.

Original languageEnglish
Pages (from-to)721-730
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume36
Issue number4
DOIs
StatePublished - 2015

Bibliographical note

Funding Information:
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: NIH UL1TR000117 to JFF and NIH 5T32 NS077889 to MM

Publisher Copyright:
© 2015 The Author(s).

Keywords

  • Ischemic stroke
  • cerebral ischemia
  • intra-arterial
  • neuroprotection
  • recanalization
  • verapamil

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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