Abstract WP111: Activation of α7 Nicotinic Acetylcholine Receptor Improves Blood-Brain Barrier Integrity in Mice with Ischemic Stroke and Bone Fracture
Background & Purpose: Stroke is an important risk factor and one of the most devastating complications for bone fracture. We showed previously that bone fracture at the acute stage of ischemic stroke worsens, and activation of α7 nicotinic acetylcholine receptor (α7 nAchR) improves stroke recovery through attenuation of inflammation. We hypothesized that activation of α7 nAchR also improves blood-brain barrier integrity.
Methods: Permanent distal middle cerebral artery occlusion (pMCAO) was performed on C57BL/6J mice followed by tibia fracture 1 day later. Mice were treated intra-peritoneally with 0.8 mg/kg PHA 568487 (PHA, α7 nAchR-specific agonist), 6 mg/kg methyllycaconitine (MLA, α7 nAchR antagonist), or saline 1 and 2 days after pMCAO. Brain water content was assessed by measuring the wet and dry weight 3 days after pMCAO. The expression of monoamine oxidase B (MAO-B) in astrocytes and tight junction proteins was quantified in the peri-infarct region using immunostained brain sections (N=6).
Results: Tibia fracture increased water content in the ischemic stroke brain (p<0.001) and MAO-B positive astrocytes (p<0.001), and decreased tight junction protein expression. Compared to saline treatment, PHA reduced and MLA increased water content and the MAO-B positive astrocytes in the brain of pMCAO and pMCAO-plus-tibia-fracture mice (p<0.05). PHA also increased and MLA decreased tight junction protein expression.
Conclusions: In addition to inhibiting inflammation, activation of α7 nAchR also reduces astrocyte oxidative stress and improves blood-brain barrier integrity. Thus, the α7 nAchR-specific agonist can be developed into a new therapy for improving recovery patients with stroke or stroke plus bone fracture.
Author Disclosures: D. Zou: None. Z. Han: None. L. Zhan: None. W. Zhu: None. S. Kang: None. C. Bao: None. A. Sadighi: None. Z. Li: None. J. Nelson: None. R. Zhang: None. H. Su: None.
- © 2016 by American Heart Association, Inc.