Document Detail


Concurrent middle cerebral artery occlusion and intra-arterial drug infusion via ipsilateral common carotid artery catheter in the rat.
MedLine Citation:
PMID:  23261656     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pre-clinical development of therapy for acute ischemic stroke requires robust animal models; the rodent middle cerebral artery occlusion (MCAo) model using a nylon filament inserted into the internal carotid artery is the most popular. Drug screening requires targeted delivery of test substance in a controlled manner. To address these needs, we developed a novel method for delivering substances directly into the ischemic brain during MCAo in the awake rat. An indwelling catheter is placed in the common carotid artery ipsilateral to the occlusion at the time of the surgical placement of the occluding filament. The internal and common carotid arteries are left patent to allow superfusion anterograde. The surgeries can be completed quickly to allow rapid recovery from anesthesia; tests substances can be infused at any given time for any given duration. To simulate clinical scenarios, the occluding filament can be removed minutes or hours later (reperfusion) followed by therapeutic infusions. By delivering drug intra-arterially to the target tissue, "first pass" loss in the liver is reduced and drug effects are concentrated in the ischemic zone. To validate our method, rats were infused with Evans blue dye either intra-arterially or intravenously during a 4 h MCAo. After a 30 min reperfusion period, the dye was extracted from each hemisphere and quantitated with a spectrophotometer. Significantly more dye was measured in the ischemic hemispheres that received the dye intra-arterially.
Authors:
Jessica A Van Winkle; Bo Chen; I-Farn Lei; Benedict Pereira; Padmesh S Rajput; Patrick D Lyden
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-20
Journal Detail:
Title:  Journal of neuroscience methods     Volume:  213     ISSN:  1872-678X     ISO Abbreviation:  J. Neurosci. Methods     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-11     Completed Date:  2013-07-25     Revised Date:  2014-02-18    
Medline Journal Info:
Nlm Unique ID:  7905558     Medline TA:  J Neurosci Methods     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  63-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Anesthesia
Animals
Brain Ischemia / pathology
Carotid Artery, Common / physiology*
Catheterization, Peripheral
Coloring Agents
Evans Blue
Functional Laterality / physiology
Infarction, Middle Cerebral Artery / pathology*
Infusions, Intravenous
Injections, Intra-Arterial
Jugular Veins
Male
Neurologic Examination
Rats
Rats, Sprague-Dawley
Reperfusion
Stroke / pathology
Sutures
Grant Support
ID/Acronym/Agency:
R01 NS075930/NS/NINDS NIH HHS; R01NSO754930-01//PHS HHS
Chemical
Reg. No./Substance:
0/Coloring Agents; 45PG892GO1/Evans Blue
Comments/Corrections

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