Chloral Hydrate Preconditioning Protects Against Ischemic Stroke via Upregulating Annexin A1.

Abstract

AIMS:

Preconditioning is promising for treating cerebral ischemic stroke. Annexin A1 (ANXA1) is a homeostatic antiinflammatory mediator that participates in countering against ischemic injuries. We investigated whether chloral hydrate preconditioning (CH) exerts neuroprotection via regulation of ANXA1 in stroke.

METHODS:

Adult male C57BL/6J mice or ANXA1 knockout (ANXA1(-/-) ) mice were randomly allocated to control (NCH) and CH groups [2%, 6%, and 10% chloral hydrate (i.p.) 1 h before the middle cerebral artery occlusion (MCAO)]. Neurological performances were evaluated by modified 7-point neurological scales and rotarod test. Cerebral infarction was analyzed by triphenyltetrazolium chloride (TTC) staining and MRI. The expression of ANXA1, pro-inflammatory (TNF-α, IL-1β, IL-6), and antiinflammatory (IL-4, IL-10, TGF-β) cytokines was investigated by RT-PCR, western blot, and immunofluorescence.

RESULTS:

Chloral hydrate preconditioning significantly improved the neurological outcomes and reduced the infarction and brain edema after ischemia. In addition, CH increased the expression of ANXA1 in the microglia, decreased the levels of TNF-α, IL-1β, and IL-6, while elevated the levels of IL-4, IL-10, and TGF-β in the MCAO mice. Furthermore, both ANXA1 blocker Boc1 (5 mg/kg, i.c.v.) or ANXA1 gene deficiency restrained the protective effects of CH against stroke.

CONCLUSIONS:

Chloral hydrate preconditioning protects against ischemic injuries through upregulating the expression of ANXA1, and the followed antiinflammatory mechanisms.

• Authors: Jiu-Hong Liu, Dan Feng, Yu-Fen Zhang, You Shang, Yan Wu, Xiao-Feng Li, Lei Pei
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 21 Issue 9 Pg. 718-26 (Sep 2015) ISSN: 1755-5949 [Electronic] England
• PMID: 26205642 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Annexin A1
• Cytokines
• Neuroprotective Agents
• Oligopeptides
• annexin A1, mouse
• Chloral Hydrate
• t-butyloxycarbonyl-methionyl-leucyl-phenylalanine

Topics

• Animals
• Annexin A1 (antagonists & inhibitors, genetics, metabolism)
• Brain (drug effects, pathology, physiopathology)
• Brain Edema (pathology, physiopathology, prevention & control)
• Brain Ischemia (drug therapy, pathology, physiopathology)
• Chloral Hydrate (administration & dosage)
• Cytokines (metabolism)
• Disease Models, Animal
• Infarction, Middle Cerebral Artery
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Motor Activity (drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Oligopeptides (administration & dosage)
• Random Allocation
• Recovery of Function (drug effects, physiology)
• Stroke (drug therapy, pathology, physiopathology)