Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke

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

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

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) 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.

Original languageEnglish (US)
Pages (from-to)2794-2799
Number of pages6
JournalStroke
Volume43
Issue number10
DOIs
StatePublished - Oct 2012

Keywords

  • IV tPA
  • embolic stroke
  • remote ischemic conditioning

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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