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Pre-existing interleukin 10 in cerebral arteries attenuates subsequent brain injury caused by ischemia/reperfusion.

Abstract
Recurrent stroke is difficult to treat and life threatening. Transfer of anti-inflammatory gene is a potential gene therapy strategy for ischemic stroke. Using recombinant adeno-associated viral vector 1 (rAAV1)-mediated interleukin 10 (IL-10), we investigated whether transfer of beneficial gene into the rat cerebral vessels during interventional treatment for initial stroke could attenuate brain injury caused by recurrent stroke. Male Wistar rats were administered rAAV1-IL-10, rAAV1-YFP, or saline into the left cerebral artery. Three weeks after gene transfer, rats were subjected to occlusion of the left middle cerebral artery (MCAO) for 45 min followed by reperfusion for 24 h. IL-10 levels in serum were significantly elevated 3 weeks after rAAV1-IL-10 injection, and virus in the cerebral vessels was confirmed by in situ hybridization. Pre-existing IL-10 but not YFP decreased the neurological dysfunction scores, brain infarction volume, and the number of injured neuronal cells. AAV1-IL-10 transduction increased heme oxygenase (HO-1) mRNA and protein levels in the infarct boundary zone of the brain. Thus, transduction of the IL-10 gene in the cerebral artery prior to ischemia attenuates brain injury caused by ischemia/reperfusion in rats. This preventive approach for recurrent stroke can be achieved during interventional treatment for initial stroke.
AuthorsQiu-Juan Liang, Mei Jiang, Xin-Hong Wang, Li-Li Le, Meng Xiang, Ning Sun, Dan Meng, Si-Feng Chen
JournalIUBMB life (IUBMB Life) Vol. 67 Issue 9 Pg. 710-9 (Sep 2015) ISSN: 1521-6551 [Electronic] England
PMID26337686 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2015 International Union of Biochemistry and Molecular Biology.
Chemical References
  • Neuroprotective Agents
  • RNA, Messenger
  • Interleukin-10
Topics
  • Animals
  • Blotting, Western
  • Brain Injuries (etiology, prevention & control)
  • Cerebral Arteries (metabolism, pathology)
  • Dependovirus (genetics)
  • Genetic Therapy
  • Immunoenzyme Techniques
  • Interleukin-10 (administration & dosage, genetics)
  • Male
  • Neuroprotective Agents (administration & dosage)
  • Oxidative Stress
  • RNA, Messenger (genetics)
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Reperfusion Injury (complications)
  • Reverse Transcriptase Polymerase Chain Reaction

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