Neuroprotective effect of acute ethanol administration in a rat with transient cerebral ischemia.

Abstract

BACKGROUND AND PURPOSE:

Ethanol consumption is inversely associated with the risk of ischemic stroke, suggesting a neuroprotective effect. In a rat model of transient cerebral ischemia, we identified ethanol as a possible treatment for acute ischemic stroke.

METHODS:

Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 hours. Five sets of experiments were conducted: to determine the dose-response effect of ethanol on brain infarction and functional outcome; to determine whether combining ethanol and hypothermia produces synergistic neuroprotection; to determine the therapeutic windows of opportunity for ethanol in stroke; to test whether ethanol promotes intracerebral hemorrhage in a hemorrhagic or ischemic stroke or after administration of thrombolytics; and to test the affect of ethanol on hypoxia-inducible factor-1α protein expression.

RESULTS:

Ethanol at 1.5 g/kg reduced infarct volume and behavioral dysfunction when administered at 2, 3, or 4 hours after middle cerebral artery occlusion. The protective effect of ethanol was not improved when paired with hypothermia. Ethanol did not promote cerebral hemorrhage in hemorrhagic or ischemic stroke in combination with recombinant tissue-type plasminogen activator or urokinase. Ethanol treatment (1.5 g/kg) increased protein levels of hypoxia-inducible factor-1α at 3 hours postreperfusion.

CONCLUSIONS:

Ethanol exerts a strong neuroprotective effect when administered up to 4 hours after ischemia, increases expression of hypoxia-inducible factor-1α, and does not promote intracerebral hemorrhage when used with thrombolytics. Ethanol is a potential neuroprotectant for acute ischemic stroke.

• Authors: Fei Wang, Yu Wang, Xiaokun Geng, Karam Asmaro, Changya Peng, Jonathon M Sullivan, Jamie Y Ding, Xunming Ji, Yuchuan Ding
• Journal: Stroke (Stroke) Vol. 43 Issue 1 Pg. 205-10 (Jan 2012) ISSN: 1524-4628 [Electronic] United States
• PMID: 22052512 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fibrinolytic Agents
• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit
• Neuroprotective Agents
• Ethanol
• Tissue Plasminogen Activator
• Urokinase-Type Plasminogen Activator

Topics

• Animals
• Brain (drug effects, metabolism, physiopathology)
• Cerebral Hemorrhage (chemically induced, drug therapy)
• Dose-Response Relationship, Drug
• Ethanol (administration & dosage, therapeutic use)
• Fibrinolytic Agents (administration & dosage)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Ischemic Attack, Transient (drug therapy, metabolism, physiopathology)
• Male
• Neuroprotective Agents (administration & dosage, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (drug effects, physiology)
• Tissue Plasminogen Activator (administration & dosage)
• Urokinase-Type Plasminogen Activator (administration & dosage)