Acute bioenergetic intervention or pharmacological preconditioning protects neuron against ischemic injury

Shimin Liu, Gehua Zhen, Rung Chi Li, Sylvain Doré

Research output: Contribution to journalArticle

Abstract

Although acute ischemic stroke has high mortality and morbidity rate but yet still has very limited treatment. In this study we have tested the concept of neuron protection by acute bioenergetic intervention or by pharmacological preconditioning with natural antioxidants. Adenosine triphosphate (ATP), pentobarbital, and suramin were encapsulated in pH-sensitive liposomes and used as bioenergy stabilizer. We induced ATP depletion model by incubating cells with media added with ATP-depleting agents for 2 hours. Treatment with bioenergy stabilizer started 10-min post inducing of ATP-depletion. The acute treatment with bioenergy stabilizer significantly increased cell viability in neuro-2a cells. In searching for a pharmacological preconditioning candidate for reducing ischemic injury, we tested cocoa-derived flavanols using bilateral common carotid artery occlusion (BCCAO). We pretreated mice with cocoa-derived flavanols (75 mg/kg) or water orally for 7 days and subjected mice for 12 minutes BCCAO. At 7 days post-ischemia, the number of surviving hippocampal CA1 neurons was significantly higher in the treated mice than in the watertreated controls. The protection from cocoa-derived flavanols was found associated with increased total antioxidant capacity in the brain. Our results indicate that for reducing acute ischemic injury bioenergetic intervention using advanced drug delivery tools is conceptually feasible, and for reducing reperfusion related secondary injury pharmacological preconditioning may provide significant protection.

Original languageEnglish (US)
JournalJournal of Experimental Stroke and Translational Medicine
Volume6
Issue number1
StatePublished - 2013

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Energy Metabolism
Adenosine Triphosphate
Pharmacology
Neurons
Common Carotid Artery
Wounds and Injuries
Antioxidants
Suramin
Pentobarbital
Liposomes
Reperfusion
Cell Survival
Therapeutics
Ischemia
Stroke
Morbidity
Mortality
Water
Brain
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Clinical Neurology
  • Cognitive Neuroscience
  • Neurology

Cite this

Acute bioenergetic intervention or pharmacological preconditioning protects neuron against ischemic injury. / Liu, Shimin; Zhen, Gehua; Li, Rung Chi; Doré, Sylvain.

In: Journal of Experimental Stroke and Translational Medicine, Vol. 6, No. 1, 2013.

Research output: Contribution to journalArticle

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