Shenfu injection improves cerebral microcirculation and reduces brain injury in a porcine model of hemorrhagic shock; SFI reduces brain injury after hemorrhagic shock

2021 ◽  
pp. 1-11
Author(s):  
Junyuan Wu ◽  
Zhiwei Li ◽  
Wei Yuan ◽  
Qiang Zhang ◽  
Yong Liang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Hemorrhagic Shock ◽  
Interleukin 6 ◽  
Aquaporin 4 ◽  
Flow Index ◽  
Sham Operation ◽  
Volume Resuscitation ◽  
Cerebral Microcirculation ◽  
Shenfu Injection ◽  
Tnf Α

BACKGROUND: Shenfu injection (SFI) is a traditional Chinese herbal medicine which has been clinically used for treatment of septic shock and cardiac shock. The aim of this study was to clarify effects of SFI on cerebral microcirculation and brain injury after hemorrhagic shock (HS). METHODS: Twenty-one domestic male Beijing Landrace pigs were randomly divided into three groups: SFI group (SFI, n = 8), saline group (SA, n = 8) or sham operation group (SO, n = 5). In the SFI group, animals were induced to HS by rapid bleeding to a mean arterial pressure of 40 mmHg within 10 minutes and maintained at 40±3 mmHg for 60 minutes. Volume resuscitation (shed blood and crystalloid) and SFI were given after 1 hour of HS. In the SA group, animals received the same dose of saline instead of SFI. In the SO group, the same surgical procedure was performed but without inducing HS and volume resuscitation. The cerebral microvascular flow index (MFI), nitric oxide synthase (NOS) expression, aquaporin-4 expression, interleukin-6, tumor necrosis factor-α (TNF-α) and ultrastructural of microvascular endothelia were measured. RESULTS: Compared with the SA group, SFI significantly improved cerebral MFI after HS. SFI up regulated cerebral endothelial NOS expression, but down regulated interleukin-6, TNF-α, inducible NOS and aquaporin-4 expression compared with the SA group. The cerebral microvascular endothelial injury and interstitial edema in the SFI group were lighter than those in the SA group. CONCLUSIONS: Combined application of SFI with volume resuscitation after HS can improve cerebral microcirculation and reduce brain injury.

Shenfu Injection Improves Cerebral Microcirculation and Reduces Brain Injury in a Porcine Model of Hemorrhagic Shock

2020 ◽  
Author(s):  
Junyuan Wu ◽  
Zhiwei Li ◽  
Wei Yuan ◽  
Qiang Zhang ◽  
Yong Liang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Hemorrhagic Shock ◽  
Interleukin 6 ◽  
Aquaporin 4 ◽  
Flow Index ◽  
Sham Operation ◽  
Volume Resuscitation ◽  
Cerebral Microcirculation ◽  
Sham Operation Group ◽  
Tnf Α

Abstract Background: The aim of this study was to clarify effects of Shenfu infusion (SFI) on cerebral microcirculation and brain injury after hemorrhagic shock (HS).Methods: Twenty-one domestic male Beijing Landrace pigs were randomly divided into three groups: SFI group (SFI, n=8), saline group (SA, n=8) or sham operation group (SO, n=5). In the SFI group, animals were induced to HS by rapid bleeding to a mean arterial pressure of 40 mmHg within 10 minutes and maintained at 40 ± 3 mmHg for 60 minutes. Volume resuscitation (shed blood and crystalloid) and SFI were given after 1 hour of HS. In the SA group, animals received the same dose of saline instead of SFI. In the SO group, the same surgical procedure was performed but without inducing HS and volume resuscitation. The cerebral microvascular flow index (MFI), nitric oxide synthase (NOS) expression, aquaporin-4 expression, interleukin 6, tumor necrosis factor-α (TNF-α) and ultrastructural of microvascular endothelia were measured.Results: Compared with the SA group, SFI significantly improved cerebral MFI after HS. SFI up regulated cerebral endothelial NOS expression, but down regulated interleukin 6, TNF-α, inducible NOS and aquaporin-4 expression compared with the SA group. The cerebral microvascular endothelial injury and interstitial edema in the SFI group were lighter than those in the SA group.Conclusions: Combined application of SFI with volume resuscitation after HS can improve cerebral microcirculation and reduce brain injury.

Abstract WP276: Drag Reducing Polymers Based Resuscitation Fluid Improves Cerebral Microcirculation After Mild Traumatic Brain Injury and Hemorrhagic Shock

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Devon Lara ◽  
Gloria Statom ◽  
Olga A Bragina ◽  
Marina V Kameneva ◽  
Edwin M Nemoto ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Arterial Pressure ◽  
Hemorrhagic Shock ◽  
Hospital Care ◽  
Microvascular Perfusion ◽  
Arterial Hypotension ◽  
Cerebral Microcirculation ◽  
Neuronal Necrosis ◽  
Resuscitation Fluid

Introduction: Hemorrhagic shock (HS), causing arterial hypotension, often occurs after traumatic brain injury (TBI). Current resuscitation fluids do not ameliorate the impaired cerebral microvascular perfusion leading to hypoxia, neuronal death, increased mortality and poor neurological outcome. Nanomolar concentrations of intravascular blood soluble drag reducing polymers (DRP) were shown to increase tissue perfusion and oxygenation and decrease peripheral vascular resistance by rheological modulation of hemodynamics. We hypothesized that the resuscitation fluid with DRP would improve cerebral microcirculation, oxygenation and neuronal recovery after TBI combined with HS (TBI+HS). Methods: Mild TBI was induced in rats by fluid percussion pulse (1.5 ATA, 50 ms duration) followed by induced by phlebotomy arterial hypotension (40 mmHg). Resuscitation fluid (lactated Ringers, LR) with DRP (DRP/LR) or without (LR) was infused to restore mean arterial pressure (MAP) to 60 mmHg for one hour (pre-hospital care), followed by re-infusion of blood to a MAP of 100 mmHg (hospital care). Using in vivo 2-photon laser scanning microscopy over the parietal cortex we monitored changes in microvascular blood flow, tissue oxygenation (NADH) and neuronal necrosis (i.v. propidium Iodide) for 5 hr after TBI+HS. Doppler cortical flow, rectal and cranial temperatures, arterial pressure, blood gases and electrolytes were monitored. Results: TBI+HS compromised brain microvascular flow leading to tissue hypoxia followed by neuronal necrosis. Resuscitation with DRP/LR compared to LR better improved cerebral microvascular perfusion (82 ± 9.7% vs. 62 ± 9.7%, respectively from pre-TBI baseline, p<0.05, n=7), attenuated capillary microtrombi formation and re-recruited collapsed during HS capillaries. Improved microvascular perfusion increased cortical oxygenation reducing hypoxia (77 ± 8.2% vs. 60 ± 10.5%, by DRP-LR vs. LR, respectively from baseline, p<0.05) and decreased neuronal necrosis (21 ± 7.2% vs. 36 ± 7.3%, respectively as a percentage of total neurons, p<0.05). Conclusions: DRP/LR resuscitation fluid is superior in the restoration of the cerebral microcirculation and neuroprotection following TBI + HS compared to volume expansion with LR.

scholarly journals Effect of estrogen and/or progesterone administration on traumatic brain injury-caused brain edema: the changes of aquaporin-4 and interleukin-6

2015 ◽  
Vol 72 (1) ◽  
pp. 33-44 ◽  
Author(s):  
Zahra Soltani ◽  
Mohammad Khaksari ◽  
Nader Shahrokhi ◽  
Gholamabbas Mohammadi ◽  
Behshad Mofid ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Interleukin 6 ◽  
Aquaporin 4

Abstract 174: Effects of Melatonin (N-Acetyl-5-Methoxytryptamine) on Inflammation and Cerebral Microcirculation After Cardiopulmonary Resuscitation in a Rat Model of Cardiac Arrest

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Juntao Hu ◽  
Guanghui Zheng ◽  
Fenglian He ◽  
Weiwei Ge ◽  
Jing Xu ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Rat Model ◽  
Animal Studies ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Flow Index ◽  
Cerebral Microcirculation ◽  
Sprague Dawley ◽  
Tnf Α

Introduction: Cerebral ischemia-reperfusion injury produces inflammation and cerebral microcirculatory dysfunction after cardiopulmonary resuscitation (CPR). Melatonin (N-acetyl-5-methoxytryptamine) has both anti-inflammatory and anti-oxidative properties. In this study, we investigated the effects of melatonin on inflammation and cerebral microcirculation after cardiopulmonary resuscitation in a rat model of cardiac arrest. Hypothesis: Melatonin decreases the systemic inflammatory response after cardiopulmonary resuscitation and will preserve cerebral microcirculation in a rat model of cardiac arrest. Method: Eighteen male Sprague Dawley rats weighing between 450-550 g were randomized into three groups: 1) sham: no ventricular fibrillation (VF) and CPR; 2) CPR control: untreated VF for 6 min followed by 8 min CPR; 3) CPR+melatonin: untreated VF for 6 min followed by 8 min CPR. Melatonin (10 mg/kg) was administered intraperitoneal (IP) in line with hypoxia-ischemia animal studies after return of spontaneous circulation (ROSC). Serum TNF- α, IL-1 β and cerebral microcirculation were measured at baseline and 6 h following ROSC. Result: Serum TNF-α and IL-1β were significantly lower in the CPR+melatonin group at 6h after ROSC compared to CPR controls ( p <0.01, Fig. 1). Animals treated with melatonin had improved cerebral microcirculation including perfused vessel density (PVD), proportion of perfused vessels (PPV) and microvascular flow index (MFI) compared to control animals ( p <0.05, Fig. 2). Conclusion: In a rat model of cardiac arrest, melatonin reduced systemic inflammation and preserved cerebral microcirculation following resuscitation.

scholarly journals TNF-α Impairs Pericyte-Mediated Cerebral Microcirculation via the NF-κB/iNOS Axis After Experimental Traumatic Brain Injury

2021 ◽  
Author(s):  
Shaorui Zheng ◽  
Cheng Wang ◽  
Long Lin ◽  
Shuwen Mu ◽  
Haibing Liu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Oxidative Damage ◽  
Laser Speckle ◽  
Immunofluorescent Staining ◽  
Cerebral Microcirculation ◽  
Bv2 Cells ◽  
Tnf Α ◽  
Severity Scores ◽  
The Impact

Abstract Background Secondary structural and functional abnormalities of the neurovascular unit are important pathological mechanisms following traumatic brain injury (TBI). The tumor necrosis factor α (TNF-α)/nuclear factor-κB (NF-κB) pathway regulates neuroinflammation and oxidative damage, which may act as triggers for pathological processes after TBI. However, the role of TNF-α/NF-κB in pericyte-mediated cerebral microcirculation are currently unknown. Methods We assessed the activity and mechanisms of the TNF-α/NF-κB signaling axis on pericyte-mediated microcirculation using the mouse controlled cortical impact model and BV2 cells. Immunofluorescent staining and western blot analysis were used to detect activation of the TNF-α/NF-κB signaling pathway and the expression of inducible nitric oxide synthase (iNOS) to evaluate the effects of the TNF-α specific inhibitor infliximab (IFX). Modified neurological severity scores, Garcia test, Nissl staining, and TUNEL staining were employed to determine the neuroprotective effects of IFX supplementation. The relative blood flow values in the capillary areas surrounding the impinging lesion were observed by Laser speckle contrast imaging. The impact of IFX on pericyte markers was assessed to evaluate whether pericyte damage was dependent on the TNF-α/NF-κB/iNOS axis to gain further insight into the mechanisms underlying the development of the microcirculation disturbance after TBI. Results Microglia were activated after TBI, and the expression of NF-κB, iNOS, a disintegrin and metalloproteinase 17, inflammatory factors, and free radicals increased around the injury areas. After lipopolysaccharide treatment, the expression of TNF-α and downstream NF-κB/iNOS in BV2 cells was significantly upregulated. Pharmacological inhibition of TNF-α via IFX significantly reduced NF-κB p65 phosphorylation and nuclear translocation and downregulated iNOS expression. Meanwhile, we found that specific inhibition of TNF-α reversed pericyte marker loss, and improved pericyte function and cerebral microcirculation perfusion after TBI, which could attenuate inflammation and oxidative damage, reduce neuronal cell damage and apoptosis, and play a neuroprotective role. Conclusion The results of this study suggested that microglia activated and released TNF-α after TBI, which promoted neuroinflammation and oxidative stress by activating downstream NF-κB/iNOS signals, and this led to pericyte-mediated disturbance of the cerebral microcirculation, which may be one of the vital mechanisms of secondary injury in TBI.

scholarly journals Visualization of three-dimensional microcirculation of rodents’ retina and choroid for studies of critical illness using optical coherence tomography angiography

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jang Ryul Park ◽  
ByungKun Lee ◽  
Min Ji Lee ◽  
Kyuseok Kim ◽  
Wang-Yuhl Oh
Keyword(s):  
Blood Flow ◽  
Optical Coherence Tomography ◽  
Severe Sepsis ◽  
Critical Illness ◽  
Hemorrhagic Shock ◽  
Optical Coherence Tomography Angiography ◽  
Flow Index ◽  
Optical Coherence ◽  
Sepsis Model ◽  
Lactate Levels

AbstractWe developed a method to measure the relative blood flow speed using optical coherence tomography angiography (OCTA) in retina and choroid, and investigated the feasibility of this method for assessing microcirculatory function in rat models of sepsis and hemorrhagic shock. Two sepsis models, 6-h severe sepsis without treatment and 30-h moderate sepsis maintaining mean arterial pressure, and volume controlled hemorrhagic shock and fluid resuscitation model were used to see the change of microcirculation. The blood flow index (BFI), which was calculated from the OCTA images to represent the average relative blood flow, was decreasing during the 6-h severe sepsis model. Its change is in parallel with the mean arterial blood pressure (MAP) and blood lactate levels. In the 30-h moderate sepsis model, the BFI was decreased while maintaining MAP, and lactate was increased. In the hemorrhagic shock model, the change of BFI is in line with MAP and lactate levels. In all models, BFI change is more sensitive in choroid than in retina. This study presents the OCTA-based retinal and choroidal microcirculatory blood flow monitoring method and shows its utility for assessment of critical illness.

scholarly journals Resuscitation from hemorrhagic shock after traumatic brain injury with polymerized hemoglobin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cynthia R. Muller ◽  
Vasiliki Courelli ◽  
Alfredo Lucas ◽  
Alexander T. Williams ◽  
Joyce B. Li ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Hemorrhagic Shock ◽  
Ischemia Reperfusion Injury ◽  
Diastolic Pressure ◽  
Ischemia Reperfusion ◽  
Treatment Strategies ◽  
Secondary Bleeding ◽  
Additional Testing ◽  
Systolic Blood Pressure Variability

AbstractTraumatic brain injury (TBI) is often accompanied by hemorrhage, and treatment of hemorrhagic shock (HS) after TBI is particularly challenging because the two therapeutic treatment strategies for TBI and HS often conflict. Ischemia/reperfusion injury from HS resuscitation can be exaggerated by TBI-induced loss of autoregulation. In HS resuscitation, the goal is to restore lost blood volume, while in the treatment of TBI the priority is focused on maintenance of adequate cerebral perfusion pressure and avoidance of secondary bleeding. In this study, we investigate the responses to resuscitation from severe HS after TBI in rats, using fresh blood, polymerized human hemoglobin (PolyhHb), and lactated Ringer’s (LR). Rats were subjected to TBI by pneumatic controlled cortical impact. Shortly after TBI, HS was induced by blood withdrawal to reduce mean arterial pressure (MAP) to 35–40 mmHg for 90 min before resuscitation. Resuscitation fluids were delivered to restore MAP to ~ 65 mmHg and animals were monitored for 120 min. Increased systolic blood pressure variability (SBPV) confirmed TBI-induced loss of autoregulation. MAP after resuscitation was significantly higher in the blood and PolyhHb groups compared to the LR group. Furthermore, blood and PolyhHb restored diastolic pressure, while this remained depressed for the LR group, indicating a loss of vascular tone. Lactate increased in all groups during HS, and only returned to baseline level in the blood reperfused group. The PolyhHb group possessed lower SBPV compared to LR and blood groups. Finally, sympathetic nervous system (SNS) modulation was higher for the LR group and lower for the PolyhHb group compared to the blood group after reperfusion. In conclusion, our results suggest that PolyhHb could be an alternative to blood for resuscitation from HS after TBI when blood is not available, assuming additional testing demonstrate similar favorable results. PolyhHb restored hemodynamics and oxygen delivery, without the logistical constraints of refrigerated blood.

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