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Ischemic postconditioning decreases cerebral edema and brain blood barrier disruption caused by relief of carotid stenosis in a rat model of cerebral hypoperfusion.

Yang F, Zhang X, Sun Y, Wang B, Zhou C, Luo Y, Ge P - PLoS ONE (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, First Bethune Hospital of Jilin University, Changchun, China.

ABSTRACT

Background and purpose: 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. 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.

Methods: Wistar 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.

Results: The 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.

Conclusions: Ischemic postconditioning is an effective method to prevent brain edema and improve BBB permeability and could be used during relief of severe carotid stenosis.

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Related in: MedlinePlus

Schematic depicting the order of surgical procedures for Wistar rats undergoing sham operation, carotid stenosis, stenosis relief and ischemic postconditioning (ischemic postconditioning consisted of 3 cycles of 30-s/30-s reperfusion/ clamping after 3 days ischemic episode).
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getmorefigures.php?uid=PMC3585273&req=5

pone-0057869-g001: Schematic depicting the order of surgical procedures for Wistar rats undergoing sham operation, carotid stenosis, stenosis relief and ischemic postconditioning (ischemic postconditioning consisted of 3 cycles of 30-s/30-s reperfusion/ clamping after 3 days ischemic episode).

Mentions: At the start of the study, the rats were assigned randomly into sham-operated group, carotid stenosis group, and ischemic postconditioning group according to a computer generated randomization schedule. In the sham-operated group, the bilateral common carotid artery was exposed, but no ligature was made. In the carotid stenosis group, the carotid stenosis was maintained 3 days before it was relieved. In the ischemic postconditioning group, three cycles of 30-s/30-s reperfusion/clamping were exerted at the end of reliving carotid stenosis (Fig. 1).


Ischemic postconditioning decreases cerebral edema and brain blood barrier disruption caused by relief of carotid stenosis in a rat model of cerebral hypoperfusion.

Yang F, Zhang X, Sun Y, Wang B, Zhou C, Luo Y, Ge P - PLoS ONE (2013)

Schematic depicting the order of surgical procedures for Wistar rats undergoing sham operation, carotid stenosis, stenosis relief and ischemic postconditioning (ischemic postconditioning consisted of 3 cycles of 30-s/30-s reperfusion/ clamping after 3 days ischemic episode).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585273&req=5

pone-0057869-g001: Schematic depicting the order of surgical procedures for Wistar rats undergoing sham operation, carotid stenosis, stenosis relief and ischemic postconditioning (ischemic postconditioning consisted of 3 cycles of 30-s/30-s reperfusion/ clamping after 3 days ischemic episode).
Mentions: At the start of the study, the rats were assigned randomly into sham-operated group, carotid stenosis group, and ischemic postconditioning group according to a computer generated randomization schedule. In the sham-operated group, the bilateral common carotid artery was exposed, but no ligature was made. In the carotid stenosis group, the carotid stenosis was maintained 3 days before it was relieved. In the ischemic postconditioning group, three cycles of 30-s/30-s reperfusion/clamping were exerted at the end of reliving carotid stenosis (Fig. 1).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, First Bethune Hospital of Jilin University, Changchun, China.

ABSTRACT

Background and purpose: 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. 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.

Methods: Wistar 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.

Results: The 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.

Conclusions: Ischemic postconditioning is an effective method to prevent brain edema and improve BBB permeability and could be used during relief of severe carotid stenosis.

Show MeSH
Related in: MedlinePlus