title: Stroke neuroprotection revisited: Intra-arterial verapamil is profoundly neuroprotective in experimental acute ischemic stroke.
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.
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, USA Sanders Brown Center on Aging, University of Kentucky, Lexington, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Maniskas
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, USA Sanders Brown Center on Aging, University of Kentucky, Lexington, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Roberts
authors.affiliation: Sanders Brown Center on Aging, University of Kentucky, Lexington, USA.
authors.forename: Ishi
authors.initials: I
authors.lastname: Aron
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, USA Department of Neurosurgery, University of Kentucky, Lexington, USA Department of Neurology, University of Kentucky, Lexington, Kentucky Department of Radiology, University of Kentucky, Lexington, USA.
authors.forename: Justin F
authors.initials: JF
authors.lastname: Fraser
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, USA Sanders Brown Center on Aging, University of Kentucky, Lexington, USA Department of Neurology, University of Kentucky, Lexington, Kentucky gregorybix@uky.edu jfr235@uky.edu.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bix
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002544:Cerebral Infarction / Q000473:pathology; D005911:Gliosis / Q000517:prevention & control; D007269:Injections, Intra-Arterial; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020521:Stroke / Q000517:prevention & control* / Q000523:psychology; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000209:etiology; D014700:Verapamil / Q000627:therapeutic use*
chemical_list: D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D014700:Verapamil
keywords: Ischemic stroke; cerebral ischemia; intra-arterial; neuroprotection; recanalization; verapamil