Effect Of Albumin Therapy On The Expression Of VEGF And Brain Edema After Cerebral Ischemia Reperfusion In Rat

AIM:Ischemic cerebral vascular disease is a common disease in clinical,and its incidence rate shows strikingly ascending tendency for the decade years.Ischemic cerebrovascular disease ranks among the leading cause of death and long-term disability.At present,the brain ischemic disease has no effective treatment.Albumin therapy is a neuroprotectant in recent years.Stroke treatment with high doses of HSA results in diminished brain injury,such as decreased brain edema and infarct size. Vascular endothelial growth factor is mitogenic,angiogenic,and also knows as vascular permeability factor.VEGF-mediated blood-brain barrier hyperpermeability was the main role,and caused increased cerebral edema and a series of secondary brain damage.At present,the albumin neuroprotective effect was just to stay in the study of hemodynamics,the relation that albumin treatment after cerebral ischemia early stages impact to VEGF expression and the brain edema has not been reported at home and abroad.Pre-tests showed that cerebral ischemia in the early expression of VEGF mRNA levels higher than normal level though,but compared with the saline group were reduced.We speculate to invest after cerebral ischemia,the effects of albumin to endogenous VEGF expression and cerebral edema.Methods:Adult male Sprague-Dawley(SD) rats were divided into three groups; sham group,saline group and albumin group.Rats were subjected to MCAo with a thread insert,2 hours later;the thread was withdrawn to resume the blood flow.Sham group without thread insert.The infarction volume was measured after TTC staining. The content of brain water was assayed by wet-dry method.The serum albumin level was determined by bromcresol green measurement.The enzyme linked immunosorbent assay(ELISA) was used to determine the protein level of VEGF of blood serum after reperfusion 6,24and48h.The temporal and spatial features of VEGF protein expression was studied by Western-blot in cerebral hemisphere. Immunohistochemistry was used to determine the VEGF positive cells.Results:1 After TTC staining,the brain showed white color because of ischemia and hypoxia.2 Neurological score:All transient MCAo rats showed focal neurological function deficits after recovery from anesthesia.Compared with the saline group,the neurological score of albumin group was significantly better at 24,48hours.3 The changes of serum albumin level:After MCAo,the serum albumin of the saline group was down-regulation comparing with the normal level.But compared with the saline group,the serum albumin level of the albumin group was up-regulation during the different time points(p<0.05).4 After cerebral ischemia reperfusion 24h,the brain water content and infarct size of the albumin group,compared with the saline group were significantly lower(p <0.05).That albumin treatment can improve ischemic brain edema after 24h,and to reduce the cerebral infarction and to protect brain tissue.5 Compared with the saline group,the extent of VEGF expression in blood serum of albumin group was decreased at 6,24 and 48 hours.It's showed that the expression of VEGF by Western Blot was lower than the level in the saline group(p<0.05).6 The main expression of VEGF in the saline group was around the infarct area within the neurons.And there are strong positive expressions in the choroid plexus, pia mater,periventricular and micro-vascular endothelial cells.The expression of VEGF in albumin group was in the neurons around the infarct area,but the intensity of cytoplasm expression was lower.And the positive expression of VEGF in the choroid plexus,leptomeninges,periventricular and microvascular is also lower than saline group.There was little expression in the microvascular in the sham group.Conclusions:1 High-dose human serum albumin therapy was highly effective in improving neurological status and in reducing infarct size and extent of brain swelling.2 Compared with the saline group,the expression of VEGF protein was decreased in the cerebral hemisphere and the serum.3 Compared with the saline group,the level of VEGF was decreased,following these places,such as choroid plexus,pia mater,periventricular and microvascular.4 There was a positive correlation between the level of VEGF and brain water content. VEGF level could reflect the brain water content.