Open AccessChloral Hydrate Preconditioning Protects Against Ischemic Stroke via Upregulating Annexin A1
Author(s) -
Liu JiuHong,
Feng Dan,
Zhang YuFen,
Shang You,
Wu Yan,
Li XiaoFeng,
Pei Lei
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12435
Subject(s) - chloral hydrate , medicine , neuroprotection , pharmacology , ischemia , anesthesia , stroke (engine) , inflammation , microglia , cerebral edema , mechanical engineering , engineering
Summary Aims Preconditioning is promising for treating cerebral ischemic stroke. Annexin A1 ( ANXA 1) is a homeostatic antiinflammatory mediator that participates in countering against ischemic injuries. We investigated whether chloral hydrate preconditioning ( CH ) exerts neuroprotection via regulation of ANXA 1 in stroke. Methods Adult male C57 BL /6J mice or ANXA 1 knockout ( ANXA 1 −/− ) 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 ANXA 1, pro‐inflammatory ( TNF ‐ α , IL ‐1 β , 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 ANXA 1 in the microglia, decreased the levels of TNF ‐ α , IL ‐1 β , and IL ‐6, while elevated the levels of IL ‐4, IL ‐10, and TGF ‐ β in the MCAO mice. Furthermore, both ANXA 1 blocker Boc1 (5 mg/kg, i.c.v .) or ANXA 1 gene deficiency restrained the protective effects of CH against stroke. Conclusions Chloral hydrate preconditioning protects against ischemic injuries through upregulating the expression of ANXA 1, and the followed antiinflammatory mechanisms.