Activation of α7 nicotinic acetylcholine receptor improves blood-brain barrier integrity

2^nd International Conference on Neuroimmunology & Therapeutics

December 01-02, 2016 Atlanta, USA

Hua Su

University of California, USA

Posters & Accepted Abstracts: J Neurol Disord

Abstract :

Stroke is an important risk factor and one of the most devastating complications of bone fracture. We showed previously that bone fracture at the acute stage of ischemic stroke worsens, and activation of �±7 nicotinic acetylcholine receptor (�±7 nAchR) improves stroke recovery through attenuation of inflammation. We hypothesized that activation of �±7 nAchR also reduce astrocyte oxidative stress and improves blood-brain barrier integrity. Stroke model was created by permanent occlusion of the distal middle cerebral artery (pMCAO). Tibia fracture was performing 1 day after pMCAO. Mice were treated intraperitoneally with 0.8 mg/ kg PHA 568487 (PHA, �±7 nAchR-specific agonist), 6 mg/kg methyllycaconitine (MLA, �±7 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 were quantified. We found tibia fracture increased water content in the ischemic stroke brain (p<0.001) and MAO-B positive astrocytes, and decreased tight junction protein expression. Compared to saline treatment, PHA treatment reduced and MLA increased water content, and MAO-B positive astrocytes in pMCAO and pMCAO plus tibia fracture mice. PHA treatment also increased and MLA decreased tight junction protein expression. Therefore, in addition to inhibiting inflammation, activation of �±7 nAchR also reduces astrocyte oxidative stress and improves blood-brain barrier integrity. Thus, the �±7 nAchR-specific agonist can be developed into a new therapy for improving recovery of patients with stroke or stroke plus bone fracture.

Biography :

Email: hua.su@ucsf.edu