Propofol neuroprotection in cerebral ischemia and its effects on low-molecular-weight antioxidants and skilled motor tasks.
BACKGROUND
Propofol is neuroprotective when administered immediately after stroke. The therapeutic window, duration of administration, and antioxidant mechanisms of propofol in neuroprotection are not known. The effects of propofol after stroke were examined in the conscious animal. The authors have previously shown that light propofol anesthesia (25 mg x kg(-1) x h(-1)) for a period of 4 h, even if delayed 1 h after the onset of ischemia, decreases infarct volume 3 days after the stroke.


METHODS
Cerebral ischemia was induced in awake Wistar rats by a local intracerebral injection of the potent vasoconstrictor, endothelin (6 pmol in 3 microl) into the striatum. Propofol treatment after ischemia was delayed up to 4 h, and the infusion period shortened from 4 h to 1 h. Infarct volume was assessed 3 or 21 days after the stroke. Neurologic outcome was evaluated on days 14-21 after ischemia. Tissue ascorbate and glutathione concentrations were evaluated at 4 h and 3 days after ischemia.


RESULTS
Infarct volumes were reduced 3 days after ischemia when propofol treatment (25 mg x kg(-1) x h(-1)) was delayed for 2 h (0.5+/-0.3 mm3) but not 4 h (2.0+/-0.9 mm3), compared with intralipid controls (2.4 +/- 0.7 mm3). The propofol infusion period of 3 h but not 1 h reduced infarct volume. Propofol treatment did not reduce infarct volume 21 days after the stroke, although motor function improvements (Montoya staircase test) were observed 14-21 days after the stroke. Propofol neuroprotection was independent of tissue ascorbate and glutathione concentrations.


CONCLUSIONS
Concurrent or delayed administration of propofol is neuroprotective 3 days after ischemia. Although there were no differences in infarct volume 21 days after ischemia, propofol-treated animals had functional improvements at this time.
Bayona
Nestor A
NA
Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada.
Gelb
Adrian W
AW
Jiang
Zongbin
Z
Wilson
John X
JX
Urquhart
Bradley L
BL
Cechetto
David F
DF
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D008297:Male; D009048:Motor Skills / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015742:Propofol / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D018696:Neuroprotective Agents; D015742:Propofol