Abstract
Background and PurposeComplications due to brain edema and breakdown of blood brain barrier are an important factor affecting the treatment effects of patients with severe carotid stenosis. In this study, we investigated the protective effects of ischemic postconditioning on brain edema and disruption of blood brain barrier via establishing rat model of hypoperfusion due to severe carotid stenosis.MethodsWistar rat model of hypoperfusion due to severe carotid stenosis was established by binding a stainless microtube to both carotid arteries. Ischemic postconditioning procedure consisted of three cycles of 30 seconds ischemia and 30 seconds reperfusion. Brain edema was evaluated by measuring cerebral water content, and blood brain barrier permeability was assayed by examining cerebral concentration of Evans' Blue (EB) and fluorescein sodium (NaF). ELISA was used to analyze the expression of MMP-9, claudin-5 and occludin. The activity and location of MMP-9 was analyzed by gelatin zymography and in situ zymography, respectively. The distribution of tight junction proteins claudin-5 and occludin was observed by immunohistochemistry.ResultsThe increased brain water content and cerebral concentration of EB and NaF were suppressed by administration of ischemic postconditioning prior to relief of carotid stenosis. Zymographic studies showed that MMP-9 was mainly located in the cortex and its activity was significantly improved by relief of carotid stenosis and, but the elevated MMP-9 activity was inhibited markedly by ischemic postconditioning. Immunohistochemistry revealed that ischemic postconditioning improved the discontinuous distribution of claudin-5 and occludin. ELISA detected that the expression of up-regulated MMP-9 and down-regulated claudin-5 and occludin caused by carotid relief were all attenuated by ischemic postconditioning.ConclusionsIschemic postconditioning is an effective method to prevent brain edema and improve BBB permeability and could be used during relief of severe carotid stenosis.
Highlights
Carotid artery stenosis remains a major public health issue in the developed countries [1]
Despite we have demonstrated in previous study that ischemic postconditioning could rescue neuronal death following early relief of carotid stenosis [34], the effects of ischemic postconditioning on brain edema and the permeability of blood-brain barrier (BBB) is still unclear, we investigated as well this issue in this study via using a rat model of cerebral hypoperfusion
Ischemic postconditioning suppressed brain edema caused by stenosis relief As shown in figure 2A, brain water content remained stable at the level of about 75.48% 60.26% in the carotid stenosis group, and no significant difference was found at any corresponding time point between the carotid stenosis group and the sham group
Summary
Carotid artery stenosis remains a major public health issue in the developed countries [1]. Data from animal experiment showed that 50% of the neurons in rat hippocampus CA1 region died at 30 days when severe bilateral carotid artery stenosis was produced [4]. Revascularization of stenotic artery at early stage and recovery of cerebral blood flow has become the treatment strategy for the patients with severe carotid stenosis [7,8]. Complications due to brain edema and breakdown of blood brain barrier are an important factor affecting the treatment effects of patients with severe carotid stenosis. We investigated the protective effects of ischemic postconditioning on brain edema and disruption of blood brain barrier via establishing rat model of hypoperfusion due to severe carotid stenosis
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