| The adenosine (ADO) mechanism is an important explaining for the protective effects of cerebral ischemic preconditioning (CIP) on neurons. The protective effects are usually referred to as brain ischemic tolerance (BIT). CIP lead to increases in synthesis and release of adenosine. The released adenosine combines with its specific receptors to play protective effects on neurons. The hypothesis was supported by evidences that the protective effects of CIP might be resembled by ADO or ADO analogues and blocked by adenosine receptor (AR) antagonists such as DPCPX. Because there are efficient inactivating mechanisms for adenosine, the enhanced level of ADO induced by CIP might not last to the occurrence of the following severe ischemic insult. So increases in number and activity of AR might play a more important role in the induction of BIT. To testify the assumption, changes of AR in rat hippocampal cellular membranes in the induction of BIT were observed using the radioligand binding method. In order to clarify which kind of subtype of AR contributes to the protective effect of CIP, changes in expression of hippocampal Al adenosine receptor (Al AR) and A2b adenosine receptor (A2bAR) in the induction of BIT were further observed using immunohistochemistry.1 Experimental study on the induction of ischemic tolerance of hippocampal neurons by CIP in ratsThe effects of duration of CIP and intervals between the CIP and the following ischemic insult on BIT were investigated using rat four-vessel occlusion global cerebral ischemic model. Fifty-four healthy SD rats were used. They were anesthetized with pentobarbital by abdominal administration. An incision of skin, 1.5cm in length, directly overlying thefirst cervical vertebra was made on the dorsal side of the neck behind the occipital bone. The paraspinal muscles were separated from the middle, and the right and left alar foramina of the first cervical vertebra were exposed. An electrocautery needle burned in advance was inserted though each alar foramen and both vertebral arteries were electrocauterized and permanently occluded. Silver ball electrodes were mounted on the parietal bone to record the electroencephalogram (EEG). The both common carotid arteries of the rats were exposed at Id after the operation under light ether anesthesia. Bilateral carotid arteries were occluded with aneurysmal clip to produce CIP and ischemic insult after the rat recoveryed from the ether anesthesia. The animals were divided into 4 groups: (1) the sham-operated group (n=6), exposing bilateral carotid arteries but without blocking blood flow; (2) 3-min ischemia group (n=6); (3) 6-min ischemia group; (4) ischemic preconditioning group (n=36), which were further divided into the following 6 groups (n=6 in each group): 3min-lh-6min (3min ischemic preconditioning-Ih reperfusion-6min ischemia, the same as the following) group; 3min-12h-6min group; 3min-ld-6min group; 3min-3d-6min group; lmin-ld-6min group; 5min-ld-6min group. During bilateral common carotid arteries occlusion, the pupils enlarged and EEG showed decreases in frequency and amplitude, even approach isoelectric level, indicated the production of global cerebral ischemia. Seven days after the operation or the last time of ischemia, the animals were decapitated and a brain slice l-4mm behind optical chiasm including hippocampus were excised coronally. After fixation and dehydration, the excised brain slices were imbedded in paraffin, sectioned in 8jim thickness, and stained with Lauth's staining. Histological changes of the hippocampus were divided into the following 4 grades 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 neuronal density (ND) of hippocampal CA1 subfield was determined by measuring the number of the surviving pyramidal neurons per 1mm linear length of the CA1.It was found that the rats in the sham-operated and 3-min ischemia groups showed no significant neuronal damage...
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