Effect of propofol on pathologic time-course and apoptosis after cerebral ischemia-reperfusion injury.
BACKGROUND
Propofol has been demonstrated to ameliorate cerebral ischemic injury and attenuate changes in multiple links of molecular reaction included in the paths to apoptosis. The experiment was aimed to evaluate whether propofol neuroprotection was mediated through the ability to regulate pathologic time-course of apoptosis.


METHODS
The effect of propofol given at a series of time points during ischemia-reperfusion period was determined using an intraluminal middle cerebral artery occlusion model in rats. The morphological changes of apoptosis under different duration of ischemia were detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin in situ nick labeling staining, and the effect of propofol on apoptosis was observed. The expression of anti-apoptotic protein bcl-2 in post-ischemia neurons and the influence of propofol was analyzed by immunochemistry staining.


RESULTS
Propofol attenuated neurological deficit, reduced infarct volumes, when given prior the onset of ischemia, during ischemia or 3 h after reperfusion. Apoptosis obviously appeared at 6 h post-reperfusion preceded by 90 min ischemia, rose to the maximum value at 24 h post-reperfusion and gradually diminished after 3 days reperfusion. Propofol inhibited apoptotic morphological changes between 6 h and 3 days post-reperfusion. Propofol enhanced the expression of anti-apoptotic protein bcl-2 in post-reperfusion neurons.


CONCLUSIONS
The pathologic outcome of focal cerebral ischemia-reperfusion injury was displayed by co-existence of apoptosis and necrosis. A short duration of ischemia induced apoptosis. The therapeutic window for propofol initiated before the onset of ischemia and lasted until early stage of reperfusion. The neuroprotection of propofol might be attributed to the inhibition of apoptosis.
Chen
L
L
Department of Anesthesiology, The Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200032, China.
Xue
Z
Z
Jiang
Hao
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002545:Brain Ischemia / Q000473:pathology*; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015742:Propofol / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology*; D012107:Research Design; D013997:Time Factors
D019253:Proto-Oncogene Proteins c-bcl-2; D015742:Propofol