AIMTo evaluate the effects of administration of hyperbaric oxygenation(HBO) when initiated at different time after acute transient ischemia. Apoptosis in the ischemic penumbra was further investigated to search for the possible mechanism.

METHODSThe male SD rats were randomly assigned to the following groups: control, HBO therapy initiated 3 h after ischemia, HBO therapy initiated 6 h after ischemia, HBO therapy initiated 12 h after ischemia. All animals were subjected to 90 min intraluminal middle cerebral artery occlusion (MCAO) with the regional cerebral blood flow monitored in vivo by laser Doppler flowmetry. HBO treatment was performed in a pressure chamber with 100% O2, 3 arm for 1 h. Neurological deficits and infarct volumes were assessed at 24 hours after ischemia. The immunohistochemical changes of apoptosis in the penumbra were evaluated by detecting the expression of cleaved Caspase-3, cleaved Caspase-9, Bcl-2, Bax and TUNEL staining.

RESULTSHBO therapy initiated at 3 and 6 hours after ischemia significantly improved the neurological function and reduced infarct volume. Meanwhile, it increased the expression of Bcl-2 protein and decreased the expression of activated Caspase-3, activated Caspase-9 and TUNEL-positive cells. However, HBO therapy administrated 12 hours after ischemia aggravated the neurological deficits and enlarged infarct volume, while it showed no significant reduction of apoptotic change compared with control.

CONCLUSIONThere is a therapeutic window for the use of HBO in acute transient cerebral ischemia in rats. HBO-treatment is highly effective in reducing infarct volume when initiated up to 6h after the onset of ischemia. Inhibition of apoptotic cell death in the penumbra appears to be the underlying protective effect of early therapy.