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Stroke. 2004 Feb;35(2):572-7. Epub 2004 Jan 15.

Mild postischemic hypothermia prolongs the time window for gene therapy by inhibiting cytochrome C release.

Author information

1
Department of Neurosurgery, Stanford University, Stanford, CA 94305-5327, USA.

Abstract

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.

[Indexed for MEDLINE]

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