BACKGROUND AND PURPOSE: We showed previously that Bcl-2 overexpression with the use of herpes simplex viral (HSV) vectors improved striatal neuron survival when delivered 1.5 hours after stroke but not when delivered 5 hours after stroke onset. Here we determine whether hypothermia prolongs the therapeutic window for gene therapy. METHODS: Rats were subjected to focal ischemia for 1 hour. Hypothermia (33 degrees C) was induced 2 hours after insult and maintained for 3 hours. Five hours after ischemia onset, HSV vectors expressing Bcl-2 plus beta-gal or beta-gal alone were injected into each striatum. Rats were killed 2 days later. RESULTS: Striatal neuron survival of Bcl-2-treated, hypothermic animals was improved 2- to 3-fold over control-treated, hypothermic animals and Bcl-2-treated, normothermic animals. Neuron survival among normothermic, Bcl-2-treated animals was not different from control normothermics or control hypothermics. Double immunostaining of cytochrome c and beta-gal demonstrated that Bcl-2 plus hypothermia significantly reduced cytochrome c release. CONCLUSIONS: Postischemic mild hypothermia extended the time window for gene therapy neuroprotection using Bcl-2 and reduced cytochrome c release.
BACKGROUND AND PURPOSE: We showed previously that Bcl-2 overexpression with the use of herpes simplex viral (HSV) vectors improved striatal neuron survival when delivered 1.5 hours after stroke but not when delivered 5 hours after stroke onset. Here we determine whether hypothermia prolongs the therapeutic window for gene therapy. METHODS:Rats were subjected to focal ischemia for 1 hour. Hypothermia (33 degrees C) was induced 2 hours after insult and maintained for 3 hours. Five hours after ischemia onset, HSV vectors expressing Bcl-2 plus beta-gal or beta-gal alone were injected into each striatum. Rats were killed 2 days later. RESULTS: Striatal neuron survival of Bcl-2-treated, hypothermic animals was improved 2- to 3-fold over control-treated, hypothermic animals and Bcl-2-treated, normothermic animals. Neuron survival among normothermic, Bcl-2-treated animals was not different from control normothermics or control hypothermics. Double immunostaining of cytochrome c and beta-gal demonstrated that Bcl-2 plus hypothermia significantly reduced cytochrome c release. CONCLUSIONS: Postischemic mild hypothermia extended the time window for gene therapy neuroprotection using Bcl-2 and reduced cytochrome c release.
Authors: Youn Hee Park; Young Mi Lee; Dong Sun Kim; Jaechan Park; Kyoungho Suk; Jong Kun Kim; Hyung Soo Han Journal: J Neuroinflammation Date: 2013-02-04 Impact factor: 8.322