Document Detail


Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke.
MedLine Citation:
PMID:  22910893     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Remote ischemic conditioning is cardioprotective in myocardial infarction and neuroprotective in mechanical occlusion models of stroke. However, there is no report on its therapeutic potential in a physiologically relevant embolic stroke model (embolic middle cerebral artery occlusion) in combination with intravenous tissue-type plasminogen activator (tPA).
METHODS: We tested remote ischemic perconditioning therapy (RIPerC) at 2 hours after embolic middle cerebral artery occlusion in the mouse with and without intravenous tPA at 4 hours. We assessed cerebral blood flow up to 6 hours, neurological deficits, injury size, and phosphorylation of Akt (Serine(473)) as a prosurvival signal in the ischemic hemisphere at 48 hours poststroke.
RESULTS: RIPerC therapy alone improved the cerebral blood flow and neurological outcomes. tPA alone at 4 hours did not significantly improve the neurological outcome even after successful thrombolysis. Individual treatments with RIPerC and intravenous tPA reduced the infarct size (25.7% and 23.8%, respectively). Combination therapy of RIPerC and tPA resulted in additive effects in further improving the neurological outcome and reducing the infarct size (50%). All the therapeutic treatments upregulated phosphorylation of Akt in the ischemic hemisphere.
CONCLUSIONS: RIPerC is effective alone after embolic middle cerebral artery occlusion and has additive effects in combination with intravenous tPA. RIPerC may be a simple, safe, and inexpensive combination therapy with intravenous tPA.
Authors:
Md Nasrul Hoda; Shahneela Siddiqui; Samuel Herberg; Sudharsan Periyasamy-Thandavan; Kanchan Bhatia; Sherif S Hafez; Maribeth H Johnson; William D Hill; Adviye Ergul; Susan C Fagan; David C Hess
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-08-21
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  43     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-25     Completed Date:  2013-01-17     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2794-9     Citation Subset:  IM    
Affiliation:
Department of Neurology, Georgia Health Sciences University, 1120 15 Street, CA 1014, Augusta, GA 30912, USA. mhoda@georgiahealth.edu
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MeSH Terms
Descriptor/Qualifier:
Administration, Intravenous
Animals
Brain / blood supply,  physiopathology
Combined Modality Therapy
Fibrinolytic Agents / administration & dosage,  therapeutic use
Infarction, Middle Cerebral Artery / complications*
Ischemic Preconditioning / methods*
Male
Mice
Mice, Inbred C57BL
Models, Animal
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism
Regional Blood Flow / physiology
Stroke / etiology*,  pathology,  therapy*
Thrombolytic Therapy / methods*
Time Factors
Tissue Plasminogen Activator / administration & dosage,  therapeutic use*
Treatment Outcome
Grant Support
ID/Acronym/Agency:
1R01NS055728/NS/NINDS NIH HHS; NS063965/NS/NINDS NIH HHS; NS070239/NS/NINDS NIH HHS; R21 NS070239/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Fibrinolytic Agents; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.4.21.68/Tissue Plasminogen Activator
Comments/Corrections
Comment In:
Stroke. 2013 Apr;44(4):e37   [PMID:  23646369 ]
Stroke. 2013 Apr;44(4):e36   [PMID:  23529915 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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