Adenovirus-mediated Bcl-X(L) expression using a neuron-specific synapsin-1 promoter protects against disseminated neuronal injury and brain infarction following focal cerebral ischemia in mice.
The effects of an adenovirus-mediated Bcl-X(L) expression, driven by a neuron-specific human synapsin-1 promoter, on the degree of injury, were examined after transient focal ischemia in mice. Therefore, injections of vehicle, of an adenoviral E1-deleted control vector (Ad-dE1), or a Bcl-X(L) vector (Ad-Syn-Bcl-X(L)) were stereotactically made in the striatum. Seven days later, focal ischemia was induced either by 30 min or 2 h of intraluminal thread occlusion. In line with previous data, 30 min of middle cerebral artery (MCA) occlusion reproducibly resulted in disseminated neuronal injury of the striatum, as revealed by cresyl violet and TUNEL 3 days after ischemia. The degree of cell injury was significantly reduced in Ad-Syn-Bcl-X(L) treated as compared with Ad-dE1 and vehicle-treated animals. On the other hand, 2 h of MCA occlusion produced reproducible infarcts both in vehicle and Ad-dE1 treated animals 24 h after ischemia. The infarct area at the level of the striatum was significantly decreased by Ad-Syn-Bcl-X(L) treatment. The present data demonstrate that an adenoviral Bcl-X(L) expression with a neuron-specific synapsin-1 promoter provides a powerful tool, which not only diminishes disseminated neuronal injury, but also protects against tissue infarction.
Kilic
Ertugrul
E
Department of Neurology, University of Göttingen, D-37075 Göttingen, Germany. ertugrul.kilic@med.uni-goettingen.de
Hermann
Dirk M
DM
Kügler
Sebastian
S
Kilic
Ulkan
U
Holzmüller
Harry
H
Schmeer
Christian
C
Bähr
Mathias
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D020520:Brain Infarction / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D016923:Cell Death / Q000235:genetics; D002560:Cerebrovascular Circulation / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D011401:Promoter Regions, Genetic / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D016704:Synapsins / Q000235:genetics*; D013778:Tetrazolium Salts; D016896:Treatment Outcome; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D016704:Synapsins; D013778:Tetrazolium Salts; D051020:bcl-X Protein; C009591:triphenyltetrazolium