title: Glial gap junctional communication involvement in hippocampal damage after middle cerebral artery occlusion.
abstract: OBJECTIVE
  Most patients with stroke caused by middle cerebral artery occlusion (MCAO) show cognitive deficit that is generally regarded as resulting from damage to the cerebral cortex rather than the hippocampus. Whether MCAO induces hippocampal damage and whether this contributes to the cognitive defects remains unclear. Here we investigate the hippocampal damage and its correlation to cognitive defects after exclusively unilateral MCAO and the underlying mechanism for that damage.
  
  
  METHODS
  Patients were assessed for hippocampal damage by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), and the Mini Mental-Status Evaluation (MMSE) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess for cognitive defects.
  
  
  RESULTS
  We provide the first evidence that patients with exclusively unilateral MCAO showed hippocampal damage characterized by an infarct-size-independent atrophy and alterations in neuronal and glial metabolites in the ipsilateral hippocampus, in parallel with cognitive impairment. Rodent MCAO also induced delayed shrinkage and pyramidal neuronal death in the ipsilateral hippocampus and an impairment of hippocampal-dependent spatial memory. Blocking Gap junctional communication (GJC) with carbenoxolone or downregulation of connexin43 (Cx43) significantly increased the survival of the pyramidal neurons in the ipsilateral hippocampus and improved behavioral scores. Furthermore, Cx43 heterozygous mice showed reduced shrinkage and metabolite abnormality in ipsilateral hippocampus after MCAO.
  
  
  CONCLUSIONS
  Astroglial GJC plays a significant role in MCAO-induced remote hippocampal damage and cognitive impairment. It might be possible to improve the cognition in patients with MCAO by manipulating interastrocytic communication via the gap junction channels.
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Xie
authors.forename: Chenju
authors.initials: C
authors.lastname: Yi
authors.forename: Xiang
authors.initials: X
authors.lastname: Luo
authors.forename: Shabei
authors.initials: S
authors.lastname: Xu
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Yu
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Tang
authors.forename: Wenhao
authors.initials: W
authors.lastname: Zhu
authors.forename: Yixing
authors.initials: Y
authors.lastname: Du
authors.forename: Lintao
authors.initials: L
authors.lastname: Jia
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Zhu
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Bitao
authors.initials: B
authors.lastname: Bu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000328:Adult; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D005260:Female; D017629:Gap Junctions / Q000378:metabolism / Q000473:pathology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley