| Preface There are inflammatory reactions and edema in the brain tissue around the infarct area after cerebral ischemia reperfusion. The inflammatory reactions are related to brain cell injury, which result in more serious edema. In inflammation responses, certain inflammatory factors can influence the expression of aquaporin 4 (AQP4) and matrix metalloproteinase 9 (MMP9) in the brain tissue. AQP4 plays an important role in the transportation of water molecules through blood-brain barrier (BBB), and MMP9 plays an important role in the damage of BBB basement membrane. Increase of these two kinds of protein can aggravate the degree of brain edema after cerebral ischemia reperfusion, which will seriously affect the patient’s condition and prognosis.Objective To study the influence on volume of infarction, the degree of brain edema, the degree of BBB damage and pathological changes, as well as the expression of AQP4 and MMP9 of applying rapamycin(RAPA) at the same time of rats cerebral ischemia-reperfusion. To explore that if the RAPA is protective on cerebral edema after focal cerebral ischemia-reperfusion injury in rats. And to make a preliminary analysis on the protection mechanism of RAPA on brain edema.Methods A focal cerebral ischemia/reperfusion rat model of middle cerebral artery occlusion (MCAO) was established by the thread inserting method. Seventy-two adult male SD rats were randomly divided into the following groups. Each group consists of 24 animals. RAPA group (group A):Rats were received 250 μg/ml RAPA (250 μg/kg body weight, i.p.) 1 hour after cerebral ischemia. Dimethyl sulfoxide (DMSO) group (group B):Rats were injected DMSO (1 ml/kg body weight, i.p.) 1 hour after cerebral ischemia. Sham-operated control group (group C):Rats were stimulated only by the operation without occluding the middle cerebral artery. The neurological deficit scores were estimated for rats after waking from anaesthesia. After 48 hours of the operation, the brain samples were taken out and processed for examining the area of cerebral infarction by triphenyltetrazolium chloride (TTC) staining, water content of the brain tissue, permeability of BBB by measuring Evans blue (EB) infiltrated into brain tissue, morphological alterations of the brain tissue by microscope and transmission electron microscope (TEM), expression of AQP4 and MMP9 by immunohistochemical technique. Six rats were examined for each index.Results ①The infarct volume reduced in RAPA-treated rats compared with DMSO group (P< 0.05). ②The water content decreased in RAPA-treated rats compared with DMSO group (P< 0.05). ③The extravasation of EB through BBB reduced in RAPA-treated rats compared with DMSO group (P< 0.01). ④The structure of brain tissues in sham-operated group was normal. Lesions were observed in the cortex of frontal and parietal lobe in the MCAO rats. There were numerous red neurons (eosinophilic degeneration) with necrosis, nuclei shrinkage, and Nissl body loss in widespread infarcted areas. Brain edema, neutrophil infiltration, and increased perivascular space were also seen. RAPA treatment markedly attenuated the pathological changes with decreased ischemic penumbral zone. ⑤The integrity of BBB in the ischemia area of DMSO group disrupted. The capillary lumen shrunk and there were edema around the capillary. The basement membrane was damaged seriously. The damages mentioned above alleviated in RAPA group. The ultrastructure of BBB in sham-operated groups were normal. ⑥The levels of AQP4 (P< 0.01) and MMP9 (P< 0.01) were lower in RAPA group than those in DMSO group.Conclusion Applying RAPA at the same time of reperfusion can reduce the cerebral infarction volume, improve the cerebral edema, minimize the degree of BBB damage and the pathology injury, and reduce the expression of AQP4 and MMP9 in brain tissue. Maybe, it was through inhibiting the immune cascade response, reduce the expression of AQP4 and MMP9, so as to reducing brain edema that RAPA played the protective role on rat brain tissue with ischemia/reperfusion injury. |
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