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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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Measurement of brain water content and cerebral concentration of EB and NaF.A, Brain water content. Following relief of carotid stenosis, brain water content increased significantly when compared with that in the carotid stenosis group at each indicated time point. However, the elevated brain water content was mitigated markedly by ischemic postconditioning. B, Cerebral concentration of Evans' Blue (EB); C, Cerebral concentration of fluorescein sodium (NaF). Relief of carotid stenosis made the cerebral level of EB and NaF increase significantly at each corresponding time point, which was inhibited by ischemic postconditioning performed administrated prior to stenosis relief. This indicated that, ischemic postconditioning is an effective method to suppress brain edema and elevated BBB permeability caused by relief of carotid stenosis. *: p<0.01, versus carotid stenosis group; #: p<0.01, versus stenosis relief group; &: p<0.05, versus stenosis relief group.
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pone-0057869-g002: Measurement of brain water content and cerebral concentration of EB and NaF.A, Brain water content. Following relief of carotid stenosis, brain water content increased significantly when compared with that in the carotid stenosis group at each indicated time point. However, the elevated brain water content was mitigated markedly by ischemic postconditioning. B, Cerebral concentration of Evans' Blue (EB); C, Cerebral concentration of fluorescein sodium (NaF). Relief of carotid stenosis made the cerebral level of EB and NaF increase significantly at each corresponding time point, which was inhibited by ischemic postconditioning performed administrated prior to stenosis relief. This indicated that, ischemic postconditioning is an effective method to suppress brain edema and elevated BBB permeability caused by relief of carotid stenosis. *: p<0.01, versus carotid stenosis group; #: p<0.01, versus stenosis relief group; &: p<0.05, versus stenosis relief group.

Mentions: As shown in figure 2A, brain water content remained stable at the level of about 75.48% ±0.26% 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. By contrast, when carotid stenosis was relieved, brain water content increased respectively to 78.37%±0.28% at day 1, 81.21%±0.34% at day 2 and 80.78%±0.29% at day 3, which were significantly higher than those in the carotid stenosis group at each corresponding time point. However, the elevated brain water content caused by stenosis relief was mitigated significantly by administration of ischemic postconditioning to 76.89%±0.19%, 77.84%±0.21%, and 76.97%±0.22% from day 1 to day 3. This result indicated that, ischemic postconditioning is an effective method to suppress brain edema caused by relief of carotid stenosis.


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)

Measurement of brain water content and cerebral concentration of EB and NaF.A, Brain water content. Following relief of carotid stenosis, brain water content increased significantly when compared with that in the carotid stenosis group at each indicated time point. However, the elevated brain water content was mitigated markedly by ischemic postconditioning. B, Cerebral concentration of Evans' Blue (EB); C, Cerebral concentration of fluorescein sodium (NaF). Relief of carotid stenosis made the cerebral level of EB and NaF increase significantly at each corresponding time point, which was inhibited by ischemic postconditioning performed administrated prior to stenosis relief. This indicated that, ischemic postconditioning is an effective method to suppress brain edema and elevated BBB permeability caused by relief of carotid stenosis. *: p<0.01, versus carotid stenosis group; #: p<0.01, versus stenosis relief group; &: p<0.05, versus stenosis relief group.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585273&req=5

pone-0057869-g002: Measurement of brain water content and cerebral concentration of EB and NaF.A, Brain water content. Following relief of carotid stenosis, brain water content increased significantly when compared with that in the carotid stenosis group at each indicated time point. However, the elevated brain water content was mitigated markedly by ischemic postconditioning. B, Cerebral concentration of Evans' Blue (EB); C, Cerebral concentration of fluorescein sodium (NaF). Relief of carotid stenosis made the cerebral level of EB and NaF increase significantly at each corresponding time point, which was inhibited by ischemic postconditioning performed administrated prior to stenosis relief. This indicated that, ischemic postconditioning is an effective method to suppress brain edema and elevated BBB permeability caused by relief of carotid stenosis. *: p<0.01, versus carotid stenosis group; #: p<0.01, versus stenosis relief group; &: p<0.05, versus stenosis relief group.
Mentions: As shown in figure 2A, brain water content remained stable at the level of about 75.48% ±0.26% 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. By contrast, when carotid stenosis was relieved, brain water content increased respectively to 78.37%±0.28% at day 1, 81.21%±0.34% at day 2 and 80.78%±0.29% at day 3, which were significantly higher than those in the carotid stenosis group at each corresponding time point. However, the elevated brain water content caused by stenosis relief was mitigated significantly by administration of ischemic postconditioning to 76.89%±0.19%, 77.84%±0.21%, and 76.97%±0.22% from day 1 to day 3. This result indicated that, ischemic postconditioning is an effective method to suppress brain edema caused by relief of carotid stenosis.

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