M.X. and C.Y. contributed equally to this work.
Glial gap junctional communication involvement in hippocampal damage after middle cerebral artery occlusion
Article first published online: 22 JUL 2011
Copyright © 2011 American Neurological Association
Annals of Neurology
Volume 70, Issue 1, pages 121–132, July 2011
How to Cite
Xie, M., Yi, C., Luo, X., Xu, S., Yu, Z., Tang, Y., Zhu, W., Du, Y., Jia, L., Zhang, Q., Dong, Q., Zhu, W., Zhang, X., Bu, B. and Wang, W. (2011), Glial gap junctional communication involvement in hippocampal damage after middle cerebral artery occlusion. Ann Neurol., 70: 121–132. doi: 10.1002/ana.22386
- Issue published online: 22 JUL 2011
- Article first published online: 22 JUL 2011
- Accepted manuscript online: 24 JAN 2011 08:57AM EST
- Manuscript Received: 21 MAY 2010
- Manuscript Accepted: 17 JAN 2010
- Manuscript Revised: 21 DEC 2009
- National Science Fund for Distinguished Young Scholars. Grant Number: 30725019
- Natural Science Foundation of China. Grant Numbers: 30971007, 81030021, 30600187
- National Basic Research Program. Grant Number: 2011CB504403
Most patients with stroke casued 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.
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.
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.
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. ANN NEUROL 2011;