title: Protective effect of carnosine after chronic cerebral hypoperfusion possibly through suppressing astrocyte activation.
abstract: OBJECTIVE
  Subcortical ischemic vascular dementia (SIVD) induced by chronic hypoperfusion is a common cause of vascular dementia. The aim of this study was to determine whether the protective effect of carnosine on white matter lesion after chronic cerebral hypoperfusion through suppressing astrocyte activation.
  
  
  METHODS
  Adult male mice (C57BL/6 strain) were subjected to permanent occlusion of the right unilateral common carotid arteries (rUCCAO) and treated with carnosine or histidine. Open field test, freezing test, Klüver-Barrera staining, immunohistochemical analyses and western blot were performed after rUCCAO.
  
  
  RESULTS
  We found that carnosine ameliorated white matter lesion and cognitive impairment after rUCCAO. Carnosine suppressed the activation of astrocyte in both wide type mice and histidine decarboxylase knockout mice. However, administration of histidine did not show the same effect. We found that there were no differences between rUCCAO group and sham group for the expression of glutamate transporter-1 (GLT-1) and glutamate/aspartate transporter (GLAST). Furthermore, carnosine significantly attenuated the increase of inflammatory cytokine interferon gama.
  
  
  CONCLUSIONS
  These data suggest carnosine induced neuroprotection during SIVD in mice is not dependent on the histaminergic pathway or the regulation of the expression of GLT-1 and GLAST, but may be due to a suppression of astrocyte activation and inflammatory cytokine release.
authors.affiliation: Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, P. R. China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, P. R. China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Bo
authors.affiliation: Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, P. R. China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
keywords: Astrocyte; carnosine; interferon gama; subcortical ischemic vascular dementia; white matter injury