Pre-existing interleukin 10 in cerebral arteries attenuates subsequent brain injury caused by ischemia/reperfusion.
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.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai, 200032, China.
Qiu-Juan
QJ
Liang
Department of Neurology, Gongli Hospital, Shanghai, 200135, China.
Mei
M
Jiang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai, 200032, China.
Xin-Hong
XH
Wang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai, 200032, China.
Li-Li
LL
Le
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai, 200032, China.
Meng
M
Xiang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai, 200032, China.
Ning
N
Sun
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai, 200032, China.
Dan
D
Meng
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai, 200032, China.
Si-Feng
SF
Chen
D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000209:etiology / Q000517:prevention & control*; D002536:Cerebral Arteries / Q000378:metabolism* / Q000473:pathology; D000229:Dependovirus / Q000235:genetics; D015316:Genetic Therapy; D007124:Immunoenzyme Techniques; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000235:genetics; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000150:complications*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016753:Interleukin-10
adeno-associated viral; gene transfer; heme oxygenase-1; interleukin-10; stroke