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 journalArticle

62 Citations (Scopus)

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 1 2012

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Tissue Plasminogen Activator
Stroke
Plasminogen Activators
Middle Cerebral Artery Infarction
Cerebrovascular Circulation
Therapeutics
Phosphorylation
Serine
Myocardial Infarction

Keywords

  • IV tPA
  • embolic stroke
  • remote ischemic conditioning

ASJC Scopus subject areas

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

Cite this

Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke. / Hoda, MD Nasrul; Siddiqui, Shahneela; Herberg, Samuel; Periyasamy Thandavan, Sudharsan; Bhatia, Kanchan; Hafez, Sherif S.; Johnson, Maribeth H; Hill, William D; Ergul, Adviye; Fagan, Susan C.; Hess, David C.

In: Stroke, Vol. 43, No. 10, 01.10.2012, p. 2794-2799.

Research output: Contribution to journalArticle

Hoda, MDN, Siddiqui, S, Herberg, S, Periyasamy Thandavan, S, Bhatia, K, Hafez, SS, Johnson, MH, Hill, WD, Ergul, A, Fagan, SC & Hess, DC 2012, 'Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke', Stroke, vol. 43, no. 10, pp. 2794-2799. https://doi.org/10.1161/STROKEAHA.112.660373
Hoda, MD Nasrul ; Siddiqui, Shahneela ; Herberg, Samuel ; Periyasamy Thandavan, Sudharsan ; Bhatia, Kanchan ; Hafez, Sherif S. ; Johnson, Maribeth H ; Hill, William D ; Ergul, Adviye ; Fagan, Susan C. ; Hess, David C. / Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke. In: Stroke. 2012 ; Vol. 43, No. 10. pp. 2794-2799.
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AU - Herberg, Samuel

AU - Periyasamy Thandavan, Sudharsan

AU - Bhatia, Kanchan

AU - Hafez, Sherif S.

AU - Johnson, Maribeth H

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AU - Ergul, Adviye

AU - Fagan, Susan C.

AU - Hess, David C

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