| Ischemic preconditioning is a phenomenon whereby a brief episode of sublethal ischemia and other nonlethal strssors produce protection against a subsequent lethal ischemic insult. Ischemic preconditioning was identified first in the heart. Subsequently, it has been demonstrated in brain, spinal cord, skeletal muscle, liver, kidney, lung and small intestine. More recently, it was also reported that an ischemic episode in one organ can augment ischemic tolerance in another organ, this phenomenon was termed as remote organ preconditioning. Most investigations on remote organ preconditioning are now focused on the heart and kidney. The question, however, whether remote organ preconditioning can also be protective to brain is still unkown. Because neurons share their genetic information with other cells, it is natural, to postulate that the brain can acquire the tolerance by a preceding stress given in a remote organ or tissue as in other cells. Therefore, we investigated the protective effects of limb ischemic preconditioning (LIP) on brain against global cerebral ischemia/reperfusion injuries.1 LIP prevents delayed death of pyramidal neurons in the CA1 hippocampus induced by ischemia /reperfusion in rats For the purpose, 48 Wistar rats with permanently occluded vertebral arteries were assigned to 4 groups:①Sham group (n=8): the bilateral common carotid arteries (BCCA) were separated, but without occluding the blood flow; ②LIP group (n=8): the bilateral femoral arteries were clamped for 10 min 3 times in a interval of 10 min; ③Cerebral ischemic group (n=8): The BCCA were clamped for 8 min and then reperfused; ④LIP+cerebral ischemia group(n=24): The BCCA were clamped for 8 min after LIP. The group was further divided into immediately, 1 d and 2 d group(n=8). Histological changes of the CA1 region of the hippocampus were examined 7d after the sham operation or the last time of ischemia under thionine staining. Histological changes of the CA1 hippocampus were divided into the following 4 grades (Histological grade, HG) under light microscope: grade 0, no neuron death; grade 1, scattered single neuron death; grade 2, death of many neurons; grade 3, death of almost complete neurons. The average of HG in the bilateral hippocampus was counted as statistical data. The neuronal density (ND) of the hippocampal CA1 subfield was determined by counting the number of surviving pyramidal neurons with intact cell membrane, full nucleus and clear nucleolus within 1 mm linear length of the CA1. The average of number of pyramidal neurons in 7 areas of the hippocampal CA1 subfield was calculated as ND. During clamping BCCA, the pupils enlarged and electroencephalogram (EEG) showed decreases in frequency and amplitude, even approaching isoelectric level, the righting reflex disappeared, indicating the production of global cerebral ischemia. No significant neuronal damage was found in the CA1 hippocampus in sham and LIP groups, whose HG was 0~1 and ND were 221±12 and 219±19, respectively. The rats in cerebral ischemic group exhibited obvious destruction of the CA1 subfield, HG (grade 2~3) was significantly higher than that in sham and LIP groups (P<0.01); while the ND (25±10) was significantly lower than that in the sham and limb ischemic groups (P<0.01), suggesting that cerebral ischemia for 8 min caused serious delayed neuronal death(DND) in the CA1 hippocampus. The damage of the CA1 hippocampus induced by 8 min cerebral ischemia was effectively prevented by LIP immediately prior to the cerebral ischemia, which represented by decreased HG (grade 0~1) and increased ND (183±20) compared with cerebral ischemia group (P<0.01). Although, HG showed some decrease (grade 2~3) and the ND showed some increase (42±11, 41±13 respectively) In LIP+cerebral ischemia 1d and 2d groups, but these difference were not significant compared with cerebral ischemia group (P>0.05). The results indicated that: ⑴ LIP with occlusion of bilateral femoral arteries 10 min 3 times in a interval of 10 min could not res... |
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