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

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 ves...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cerebral blood flow and metabolism 2016-04, Vol.36 (4), p.721-730
Main Authors: Maniskas, Michael E, Roberts, Jill M, Aron, Ishi, Fraser, Justin F, Bix, Gregory J
Format: Article
Language:English
Subjects:
Acute Disease
Animals
Apoptosis - drug effects
Behavior, Animal - drug effects
Brain Ischemia - complications
Brain Ischemia - drug therapy
Brain Ischemia - psychology
Calcium Channel Blockers - therapeutic use
Cell Survival - drug effects
Cerebral Infarction - pathology
Gliosis - prevention & control
Injections, Intra-Arterial
Male
Mice
Mice, Inbred C57BL
Neurons - drug effects
Neuroprotective Agents - therapeutic use
Original
Stroke - prevention & control
Stroke - psychology
Vasospasm, Intracranial - drug therapy
Vasospasm, Intracranial - etiology
Verapamil - therapeutic use
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0271-678X
1559-7016
DOI:10.1177/0271678X15608395