Neuroprotective effects of hyperthermic preconditioning on infarcted volume after middle cerebral artery occlusion in rats: role of adenosine receptors.
OBJECTIVE
There are still only a limited number of studies regarding the neuroprotective effects of hyperthermic preconditioning on regional brain ischemia or regarding the role of adenosine A1 receptors in such pretreatment. We examined the effects of hyperthermic pretreatment on infarcted volume after middle cerebral artery occlusion (MCAO), as well as the contribution of A1 receptors, to the responses in rats.


METHODS
Prospective, randomized animal study.


METHODS
An animal research laboratory in a medical university.


METHODS
Male Wistar rats (200-250 g).


METHODS
All animals were anesthetized with isoflurane during each pretreatment, as well as for MCAO. The animals were assigned as follows: (i) sham-control group (n = 8), which was maintained at normothermia (37 +/- 0.2 degrees C pericranial temperature) for 15 mins, then kept in an awake state for 0.5, 3, 6, 18, 24, or 48 hrs before 2-hr MCAO; (ii) hyperthermia group (n = 8), which was subjected to 42 +/- 0.5 degrees C for 15 mins, and then received the same treatment as the sham group; (iii) DPCPX (a selective central adenosine receptor antagonist)-treated control group, which was given the agent before normothermia pretreatment, then kept for a recovery time of 0.5 or 24 hrs (n = 8 in each group) before MCAO; (iv) DPCPX plus hyperthermia-treated group, which was administered the agent at the same dose as the control before hyperthermic exposure, then selected for each recovery time (n = 8 in each group) before MCAO; (v) DPCPX-ischemic group, to which the agent was administered before MCAO (n = 8); and (vi) vehicle-ischemic group, in which peanut oil as a vehicle, instead of DPCPX, was injected before MCAO (n = 8). Values are expressed as mean +/- se. Statistical analysis was done by analysis of variance, followed by Scheffe's F test, Mann-Whitney U test, or the chi-square test as appropriate (p <.05).


RESULTS
The infarcted volume in hyperthermic animals kept for 18 or 24 hrs before the occlusion procedure was significantly smaller than in the sham controls, but not in rats kept for 0.5, 3.0, 6.0, and 48 hrs. DPCPX partially reversed the reduction in infarcted volume that was induced by hyperthermic preconditioning after focal ischemia, whereas the agent itself did not affect the volume after ischemia.


CONCLUSIONS
These data indicate that hyperthermic pretreatment reduces the effects on MCAO-induced cerebral infarction, possibly via a partial mediation of the central adenosine receptors in the brain. The results also suggest a need for further studies to define the relationship between heat shock proteins and central adenosine receptors in preconditioning.
Xu
Hui
H
Department of Anesthesiology and Emergency Medicine and the Intensive Care Unit, Kagawa Medical University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan.
Aibiki
Mayuki
M
Nagoya
Junko
J
D000818:Animals; D001921:Brain / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology* / Q000517:prevention & control; D006979:Hyperthermia, Induced; D019194:Ischemic Preconditioning; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology*; D011446:Prospective Studies; D058915:Purinergic P1 Receptor Antagonists; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine