Hypothermic preconditioning increases survival of purkinje neurons in rat cerebellar slices after an in vitro simulated ischemia.
BACKGROUND
A period of hypothermia before ischemia (hypothermic preconditioning) induces a delayed phase of ischemic tolerance in rat brain. However, whether hypothermic preconditioning induces an acute phase (within a few hours after the hypothermia) of ischemic tolerance remains unknown. This study was designed to determine the time window of the hypothermic preconditioning-induced acute phase of neuroprotection, which is useful information for situations during surgery with anticipated ischemic episodes, and its involved mechanisms.


METHODS
Survival of Purkinje cells in rat cerebellar slices was evaluated after a 20-min oxygen-glucose deprivation (OGD, in vitro simulated ischemia) followed by a 4-h recovery. Mild hypothermia (33 degrees C) for 20 min was applied at various times before the OGD.


RESULTS
The hypothermia applied immediately to 3 h before the OGD equally effectively reduced OGD-induced Purkinje cell death/injury. Glibenclamide, a selective KATP channel blocker; 8-cyclopentyl-1,3-dipropylxanthine, a selective adenosine A1 receptor antagonist; and farnesyl protein transferase inhibitor III, a selective inhibitor to reduce Ras farnesylation, abolished hypothermic preconditioning-induced neuroprotection when applied during the hypothermia. OGD increased the expression of high-mobility group I(Y) proteins, which are nuclear transcription factors to enhance the expression of putatively damaging proteins such as cyclooxygenase-2, in cerebellar slices. This increase was attenuated by hypothermic preconditioning.


CONCLUSIONS
Hypothermic preconditioning induces an acute phase of neuroprotection. This neuroprotection depends on activation of the signaling molecules, adenosine A1 receptors, KATP channels, and Ras. Inhibition of putatively damaging proteins via the effects of hypothermic preconditioning on high-mobility group I(Y) expression may also be involved in hypothermic preconditioning-induced neuroprotection.
Yuan
Hui-Bih
HB
Department of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia, USA.
Huang
Yueming
Y
Zheng
Shuqiu
S
Zuo
Zhiyi
Z
D000818:Animals; D001921:Brain / Q000098:blood supply*; D002545:Brain Ischemia / Q000473:pathology*; D002470:Cell Survival; D005905:Glyburide / Q000494:pharmacology; D007036:Hypothermia, Induced; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D017368:Protein Prenylation / Q000187:drug effects; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005905:Glyburide