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The shot-time protective effect of hypoxic preconditioning on ischemia/reperfusion brain


To observe that hypoxic preconditioning (HP) plays a protective role on ischemia/reperfusion (I/R) brain within a short period. This experiment proved that HP can protect I/R brain by abating death and apoptosis of cells in the hippocampus; furthermore, HP also improved cognition at the fifth day after I/R.


Male Sprague–Dawley rats (250–300 g) were used in this experiment. Rats were divided into four groups randomly -sham group, control group (I/R), A group and B group – 16 rats in each group.

Ischemia was induced by withdrawal of 6–10 ml blood from the jugular catheter so as to reduce the mean arterial blood pressure to 25–30 mmHg. The carotids were then occluded with aneutysm clips, and was confirmed by the presence of an isoelectric electroencephalogram. To terminate ischemia, shed blood was reinfused, and the aneutysm clips were removed.

HP refers to rats exposed to 8% O2 for 3 hours before I/R. The sham group was without HP nor I/R, the control group received I/R without HP. The A group and B group endured I/R with HP before 1 day and 2 days, respectively.

The rats underwent a behavioral test (water maze, Passive Avoidance Task) on the fifth day after I/R followed by histopathology and TUNEL analysis. Histopathology and TUNEL analysis were performed for death and apoptosis of hippocampus cells, respectively.

All values are expressed as means ± SEM in experiments. Statistical analysis was assessed by one-way ANOVA. P < 0.05 was considered significant to reject the null hypothesis.


Histopathology showed that I/R resulted in tissue loss and necrosis in the CA1 and CA3 regions, death cells in the control group increased compared with the sham group, P < 0.01.The numbers of necrosis cells in CA1 and CA3 of the A group and B group all were significantly lower than the control group, P < 0.01. Moreover there were less death cells in the B group than in the A group P < 0.05, but there was no difference between the CA1 and CA3 regions. In the TUNEL staining assay, the apoptotic cells were stained brown. The number of TUNEL-positive cells was higher in the sham group than in the control group, P < 0.01. The number of apoptotic cells in the control group is more than in the A and B groups (P < 0.01), the degree of apoptosis was less in the B group compared with the A group, P < 0.05. There was no difference between CA1 and CA3 regions in all groups. The water maze and Passive Avoidance Task showed that the learning and memory ability of rats in the control group was injured after I/R, contrasting with the sham group P < 0.05. HP can improve cognition; learning and remembering ability in the A group and B group was significantly better than the control group, P < 0.05, especially in the B group. The movement test also offered similar result as these

That I/R can injure the brain has been confirmed by many authors; furthermore, I/R can also impair learning and memory ability. HP was discovered to be a protective method against I/R injury recently. In our experiment, HP can relieve necrosis and apoptosis of the hippocampus CA1 and CA3 regions. Moreover HP improved cognition and movement at day 5 after I/R obviously. From these results it was discovered that HP applied 2 days before I/R can produce more effective function than at 1 day before I/R. In a word, HP can improve cognition a short time after the brain receives I/R, and it is possible that HP played this role by deceasing necrosis and apoptosis cells in CA1 and CA3 of the hippocampus.

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Wang, X. The shot-time protective effect of hypoxic preconditioning on ischemia/reperfusion brain. Crit Care 10 (Suppl 1), P444 (2006).

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