Experimental stroke protection induced by 4-hydroxybenzyl alcohol is cancelled by bacitracin.

Abstract

Induction of protein disulfide isomerase (PDI) is validated as a main mechanism by which 4-hydroxybenzyl alcohol (4-HBA), an active principle of Gastrodia elata Blume, reduces cerebral infarct volumes in a murine model of focal brain ischemia/reperfusion. In contrast to its position isomers, i.e. 3-hydroxybenzyl alcohol (3-HBA) and 2-hydroxybenzyl alcohol (2-HBA), and to aliphatic diols (1,4-butanediol and 1,5-pentanediol), 4-HBA administered intravenously at 25 mg/kg protected mice, significantly reducing total, cortical and sub-cortical infarct volumes by 42, 28 and 55%, respectively. All compounds, 4-HBA included, were devoid of antioedematous properties. Only the stroke protective 4-HBA, but neither 3-HBA nor 2-HBA, was capable of significantly inducing PDI in intact mouse brains. Stroke protection was fully prevented by bacitracin (500 mg/kg), a known inhibitor of PDI, which, without affecting basal brain PDI levels, altered the ability of 4-HBA to induce significantly PDI in intact brains. Taken as a whole, our data indicate that stroke protection induced by 4-HBA involves PDI as a key player, making this protein a valuable target to control brain injury disorders. The fact that 4-HBA, at doses up to 200mg/kg, was devoid of neurotoxicity in the rotarod test is also a decisive element to promote the neuroprotective use of this plant compound.

• Authors: Elodie Descamps, Maud Petrault-Laprais, Pierre Maurois, Nicole Pages, Pierre Bac, Régis Bordet, Joseph Vamecq
• Journal: Neuroscience research (Neurosci Res) Vol. 64 Issue 2 Pg. 137-42 (Jun 2009) ISSN: 1872-8111 [Electronic] Ireland
• PMID: 19428693 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzyl Alcohols
• Neuroprotective Agents
• Bacitracin
• 4-hydroxybenzyl alcohol
• Protein Disulfide-Isomerases

Topics

• Animals
• Bacitracin (pharmacology)
• Benzyl Alcohols (chemistry, therapeutic use, toxicity)
• Brain (drug effects, enzymology, pathology)
• Infarction, Middle Cerebral Artery (complications, drug therapy, etiology, pathology)
• Ischemic Attack, Transient (drug therapy, etiology, pathology)
• Isomerism
• Mice
• Mice, Inbred C57BL
• Neuroprotective Agents (therapeutic use, toxicity)
• Protein Disulfide-Isomerases (antagonists & inhibitors, biosynthesis)
• Structure-Activity Relationship