Hypertonic Saline Solution Reduces Microcirculatory Dysfunction and Inflammation in a Rat Model of Brain Death

Correia, Cristiano de Jesus; Armstrong, Roberto; Carvalho, Priscila O.; Simas, Rafael; Sanchez, Daniela Crisina Janolli; Breithaupt‐Faloppa, Ana Cristina; Sannomiya, Paulina; Moreira, Luíz Felipe Pinho

doi:10.1097/shk.0000000000001169

Cited by 13 publications

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“…It has been well documented that BD induces hypoperfusion in the mesenteric microcirculation, which is correlated to the reduction in the level of serum corticosterone in male rats [14,16]. Correia et al (2019) [16] described that microcirculatory hypoperfusion after BD is reduced by hypertonic saline infusion, by increase in the levels of eNOS and endothelin‐1 expression, which play key roles in the inflammatory process in vascular wall and vessel tone regulator. Estrogens exert increased bioavailability of nitrous oxide (NO) in the vascular system through nongenomic pathway, once estradiol binds to estrogen receptor‐α, leading to eNOS (endothelial isozyme) phosphorylation/activation [17].…”

Section: Discussionmentioning

confidence: 99%

Treatment with 17β‐estradiol protects donor heart against brain death effects in female rat

et al. 2020

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The viability of donor organs is reduced by hemodynamic and immunologic alterations caused by brain death (BD). Female rats show higher heart inflammation associated with the reduction in female sex hormones after BD. This study investigated the effect of 17b-estradiol (E2) on BD-induced cardiac damage in female rats. Groups of female Wistar rats were assigned: Sham-operation (Sham), brain death (BD), treatment with E2 (50 lg/ml, 2 ml/h) 3 h after BD (E2-T3), or immediately after BD confirmation (E2-T0). White blood cell (WBC) count was analyzed; cytokines and troponin-I were quantified. Heart histopathological changes and expression of endothelial nitric oxide synthase, endothelin-1, intercellular adhesion molecule-1, BCL-2, and caspase-3 were evaluated. Cardiac function was continuously assessed for 6 h by left ventricular pressure-volume loop analysis. E2 decreased the BD-induced median serum concentration of troponin-I (BD:864.2 vs. E2-T0:401.4; P = 0.009), increased BCL-2 (BD:0.086 vs. E2-T0:0.158; P = 0.0278) and eNOS median expression in the cardiac tissue (BD:0.001 vs. E2-T0:0.03 and E2-T3:0.0175; P < 0.0001), and decreased caspase-3 (BD:0.025 vs. E2-T0:0.006 and E2-T3:0.019; P = 0.006), WBC counts, leukocyte infiltration, and hemorrhage. 17b-estradiol treatment was effective in reducing cardiac tissue damage in brain-dead female rats owing to its ability to reduce leukocyte infiltration and prevent cardiomyocyte apoptosis.

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Section: Discussionmentioning

confidence: 99%

Treatment with 17β‐estradiol protects donor heart against brain death effects in female rat

et al. 2020

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“…B, Likewise, the VEGF protein expression (red) in the GFAP-positive TNC1 astrocytes (green) was obviously increased at 24 h in the OGD group compared with that in the control group; however, its expression was decreased in the HS group compared with those in the corresponding groups. 33,34,[37][38][39][40] An animal experiment found that HS may ameliorate the brain edema and brain injury induced by traumatic brain injury by reducing TNF-ɑ-and IL-1β-mediated pro-inflammatory activation. 25,31 In this study, the in vitro and in vivo results show that HS can reduce the activation of the NLRP3 inflammasome and its adaptor protein apoptosis-associated speck-like protein (ASC) in microglia.…”

Section: F I G U R Ementioning

confidence: 99%

Hypertonic saline mediates the NLRP3/IL‐1β signaling axis in microglia to alleviate ischemic blood‐brain barrier permeability by downregulating astrocyte‐derived VEGF in rats

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Introduction The aim of this study was to explore whether the antibrain edema of hypertonic saline (HS) is associated with alleviating ischemic blood‐brain barrier (BBB) permeability by downregulating astrocyte‐derived vascular endothelial growth factor (VEGF), which is mediated by microglia‐derived NOD‐like receptor protein 3 (NLRP3) inflammasome. Methods The infarct volume and BBB permeability were detected. The protein expression level of VEGF in astrocytes in a transient focal brain ischemia model of rats was evaluated after 10% HS treatment. Changes in the NLRP3 inflammasome, IL‐1β protein expression, and the interleukin‐1 receptor (IL1R1)/pNF‐кBp65/VEGF signaling pathway were determined in astrocytes. Results HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulates IL‐1β expression by inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulates VEGF expression by inhibiting the phosphorylation of NF‐кBp65 mediated by IL‐1β in astrocytes. Conclusions HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulated IL‐1β expression via inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulated VEGF expression through inhibiting the phosphorylation of NF‐кBp65 mediated by IL‐1β in astrocytes.

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“…This study has some limitations. We used an investigation time of 3 h, which is usually the standard time for microcirculatory studies in this model [10,12]. However, the coagulation phenomenon is installed immediately after BD induction and the perfusion compromise is maintained [11].…”

Section: Discussionmentioning

confidence: 99%

“…Previously, to identify mechanisms involved in the microcirculatory perfusion compromise after BD, we focused on vascular elements such as NO and endothelin. We showed that after BD, increase in eNOS expression can enhance mesenteric microvascular perfusion [10] and that females present higher eNOS protein expression, despite the reduction in estradiol triggered by BD, sustaining NO synthesis and controlling vascular tone [12]. BD male animals did not show significant reduction in eNOS in the mesentery [10].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have pointed to microcirculatory changes in male rats subjected to BD, suggesting that hypoperfusion could reduce the viability of various organs [5–11]. In female rats, the initially high estradiol concentration before BD and elevated expression of eNOS seemed to favour the maintenance of microvascular perfusion/flow [12].…”

Section: Introductionmentioning

confidence: 99%

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Sex differences in the coagulation process and microvascular perfusion induced by brain death in rats

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Summary Brain death (BD) leads to a systemic inflammation associated with the activation of coagulation, which could be related to decreased microcirculatory perfusion. Evidence shows that females exhibit higher platelet aggregability than males. Thus, we investigated sex differences in platelets, coagulation and microcirculatory compromise after BD. BD was induced in male and female (proestrus) Wistar rats. After 3 h, we evaluated: (i) intravital microscopy to evaluate mesenteric perfusion and leucocyte infiltration; (ii) platelet aggregation assay; (iii) rotational thromboelastometry; and (iv) Serum NOx‐. Female rats maintained the mesenteric perfusion, whereas male reduced percentage of perfused vessels. Male BD presented higher platelet aggregation than the controls. In contrast, female BD had lower platelet aggregation than the control. Thromboelastometry indicated a reduction in clot firmness with increased clotting time in the female group compared with the male group. Serum NOx‐ level in female BD was higher than that in the male BD and female control. There is sex dimorphism in platelet function and clotting process, which are altered in different ways by BD. Thus, it is possible to connect the reduction in microcirculatory perfusion in males to intravascular microthrombi formation and the maintenance of perfusion in females to a higher inflammatory response and NO synthesis.

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Hypertonic Saline Solution Reduces Microcirculatory Dysfunction and Inflammation in a Rat Model of Brain Death

Abstract: HSS may improve the density of mesenteric perfused small vessels due to its effects on eNOS and endothelin-1 protein expression, and reduces inflammation by decreasing leukocyte adhesion and migration in a rat model of BD.

Cited by 13 publications

References 30 publications

Treatment with 17β‐estradiol protects donor heart against brain death effects in female rat

Treatment with 17β‐estradiol protects donor heart against brain death effects in female rat

Hypertonic saline mediates the NLRP3/IL‐1β signaling axis in microglia to alleviate ischemic blood‐brain barrier permeability by downregulating astrocyte‐derived VEGF in rats

Sex differences in the coagulation process and microvascular perfusion induced by brain death in rats

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