bims-heshmo Biomed News
on Trauma hemorrhagic shock — molecular basis
Issue of 2021–04–18
twelve papers selected by
Andreia Luís, Ludwig Boltzmann Institute
  1. Four-Factor Prothrombin Complex Concentrate in Adjunct to Whole Blood in Trauma-Related Hemorrhage: Does Whole Blood Replace the Need for Factors?
  2. Bicarbonate Ringer's solution for early resuscitation in hemorrhagic shock rabbits.
  3. Improved Cerebral Perfusion Pressure and Microcirculation by Drag Reducing Polymer-Enforced Resuscitation Fluid After Traumatic Brain Injury and Hemorrhagic Shock.
  4. The use of multiplexing to identify cytokine and chemokine networks in the immune-inflammatory response to trauma.
  5. The History of Hemorrhagic Shock and Damage Control Resuscitation.
  6. Interleukin-28A maintains the intestinal epithelial barrier function through regulation of claudin-1.
  7. Chinese expert consensus on diagnosis and treatment of trauma-induced hypercoagulopathy.
  8. Clinical implications of serum myoglobin in trauma patients: A retrospective study from a level 1 trauma center.
  9. Supplemental oxygen therapy in trauma patients: an exploratory registry-based study.
  10. Changes in extracellular cytokines in predicting disease severity and final clinical outcome of patients with blunt chest trauma.
  11. A case-control study of risk factors for survival after laparotomy in patients with pancreatic trauma.
  12. Divergent Functions of Tissue-Resident and Blood-Derived Macrophages in the Hemorrhagic Brain.
  1. J Trauma Acute Care Surg. 2021 Mar 16.
    Four-Factor Prothrombin Complex Concentrate in Adjunct to Whole Blood in Trauma-Related Hemorrhage: Does Whole Blood Replace the Need for Factors?
    Muhammad Khurrum, Michael Ditillo, Omar Obaid, Tanya Anand, Adam Nelson, Mohamad Chehab, Daniel James Kitts, Molly Douglas, Letitia Bible, Bellal Joseph.
       BACKGROUND: The use of whole blood (WB) for the treatment of hemorrhagic shock and coagulopathy is increasing in civilian trauma patients. Four-factor prothrombin complex concentrate (4-PCC) in adjunct to component therapy showed improved outcomes in trauma patients. Our study aims to evaluate the outcomes of trauma patients who received 4-PCC+WB compared to WB alone.
    METHODS: We performed a three-year (2015-2017) analysis of the American College of Surgeons-Trauma Quality Improvement Program database. All adult (age ≥18 years) trauma patients who received WB were included. We excluded patients who were on preinjury anticoagulants. Patients were stratified into two groups: 4-PCC+WB versus WB alone, and matched in a 1:2 ratio using propensity score matching. Outcome measures were packed red blood cells, plasma, platelets, and cryoprecipitate transfused, in-hospital complications, hospital and ICU length of stay (LOS) among survivors, and mortality.
    RESULTS: A total of 252 patients (4-PCC+WB, 84; WB alone, 168) were matched. Mean age was 47±21 years; 63% were males; median injury severity score was 30 [21-40], and 87% had blunt injuries. Patients who received 4-PCC+WB had decreased requirement for pRBC (8 units vs. 10 units; p=0.04) and FFP (6 units vs. 8 units; p=0.01) transfusion, lower rates of acute kidney injury (p=0.03), and ICU LOS (5 days vs. 8 days, p=0.01) compared to WB alone. There was no difference in the platelet transfusion (p=0.19), cryoprecipitate transfusion (p=0.37), hospital LOS (p=0.72), and in-hospital mortality (p=0.72) between the two groups.
    CONCLUSION: Our study demonstrates that the use of 4-PCC as an adjunct to WB is associated with a reduction in transfusion requirements and ICU LOS compared to WB alone in the resuscitation of trauma patients. Further studies are required to evaluate the role of PCC with WB in the resuscitation of trauma patients.
    LEVEL OF EVIDENCE: Level III Therapeutic.
    DOI:  https://doi.org/10.1097/TA.0000000000003184
  2. Ann Transl Med. 2021 Mar;9(6): 462
    Bicarbonate Ringer's solution for early resuscitation in hemorrhagic shock rabbits.
    Long Wang, Jingsheng Lou, Jiangbei Cao, Tao Wang, Jing Liu, Weidong Mi.
       Background: Fluid resuscitation is important for correcting hypovolemia. Isotonic crystalloids are the preferred solution for the initial clinical management of patients with multiple traumas. Bicarbonated Ringer's solution (BRS), offering physiological levels of bicarbonate ions and electrolyte ions, can be used for supplementing missing extracellular fluid and correcting metabolic acidosis. We here investigated the effects of BRS on the resuscitation of hemorrhagic shock models and compared the resuscitation performance of three crystalloids, including BRS, acetated Ringer's solution (ARS), and normal saline.
    Methods: Thirty adult male New Zealand rabbits were randomly divided into five groups (n=6): a sham operation group (Sham group), an operation without fluid therapy group (Shock group), a BRS group, an ARS group, and a normal saline group (Saline group). The New Zealand rabbits experienced rapid bloodletting to shock status and maintained for 20 minutes except Sham group. The status of shock was maintained in the Shock group. The fluid was infused at a rate of 60 mL/kg per hour for 1.5 hours in three fluid therapy group. Measurement of vital signs, arterial blood gas tests, blood biochemistry, hematoxylin and eosin (HE) staining of lung tissue, TUNEL staining of the liver and kidney tissues, and analysis of intestinal flora were performed.
    Results: The reduction in both base excess (BE) and bicarbonate ion (HCO3 -) caused by acidosis in rabbits with hemorrhagic shock was significantly improved in the BRS group when compared with the Saline group at infusion for 30 minutes (T3) and 30 minutes after infusion (T5) (BRS group vs. Saline group, BE: at T3, -4.83±3.60 vs. -12.50±3.27 mmol/L, P<0.01; at T5, -3.67±4.37 vs. -11.00±2.76 mmol/L, P<0.01; HCO3 -: at T3, 22.15±2.63 vs. 15.42±3.03 mmol/L, P<0.01; at T5, 23.15±2.9 vs. 16.23±3.07 mmol/L, P<0.01). Compared with Shock group, liver cell apoptosis due to hemorrhagic shock was relieved in both the BRS group and ARS group (BRS group vs. Shock group: 19.1±3.3 vs. 28.1±6.1, P<0.05; ARS group vs. Shock group: 19.8±5.4 vs. 28.1±6.1, P<0.05).
    Conclusions: During resuscitation of hemorrhagic shock, BRS, a novel perioperative balanced crystalloid, is more effective than normal saline in maintaining acid-base balance and in protecting tissues and organs.
    Keywords:  Traumatic hemorrhagic shock; bicarbonate Ringer’s solution (BRS); early fluid resuscitation
    DOI:  https://doi.org/10.21037/atm-21-97
  3. Acta Neurochir Suppl. 2021 ;131 289-293
    Improved Cerebral Perfusion Pressure and Microcirculation by Drag Reducing Polymer-Enforced Resuscitation Fluid After Traumatic Brain Injury and Hemorrhagic Shock.
    Denis E Bragin, Olga A Bragina, Alex Trofimov, Lucy Berliba, Marina V Kameneva, Edwin M Nemoto.
      Hemorrhagic shock (HS) after traumatic brain injury (TBI) reduces cerebral perfusion pressure (CPP) and cerebral blood flow (CBF), increasing hypoxia and doubling mortality. Volume expansion with resuscitation fluids (RFs) for HS does not improve CBF and tissue oxygen, while hypervolemia exacerbates brain edema and elevates intracranial pressure (ICP). We tested whether drag-reducing polymers (DRPs), added to isotonic Hetastarch (HES), would improve CBF but prevent ICP increase. TBI was induced in rats by fluid percussion, followed by controlled hemorrhage to mean arterial pressure (MAP) = 40 mmHg. HES-DRP or HES was infused to MAP = 60 mmHg for 1 h, followed by blood reinfusion to MAP = 70 mmHg. Temperature, MAP, ICP, cortical Doppler flux, blood gases, and electrolytes were monitored. Microvascular CBF, tissue hypoxia, and neuronal necrosis were monitored by two-photon laser scanning microscopy 5 h after TBI/HS. TBI/HS reduced CPP and CBF, causing tissue hypoxia. HES-DRP (1.9 ± 0.8 mL) more than HES (4.5 ± 1.8 mL) improved CBF and tissue oxygenation (p < 0.05). In the HES group, ICP increased to 23 ± 4 mmHg (p < 0.05) but in HES-DRP to 12 ± 2 mmHg. The number of dead neurons, microthrombosis, and the contusion volume in HES-DRP were significantly less than in the HES group (p < 0.05). HES-DRP required a smaller volume, which reduced ICP and brain edema.
    Keywords:  Arterial pressure; Cerebral blood flow; Cerebral perfusion pressure; Drag-reducing polymer; Hemorrhagic shock; Hetastarch; Hypoxia; Intracranial pressure; Traumatic brain injury
    DOI:  https://doi.org/10.1007/978-3-030-59436-7_54
  4. Antioxid Redox Signal. 2021 Apr 16.
    The use of multiplexing to identify cytokine and chemokine networks in the immune-inflammatory response to trauma.
    Jillian Bonaroti, Sultan Abdelhamid, Upendra Kar, Jason Sperry, Ruben Zamora, Rami Ahmd Namas, Todd McKinley, Yoram Vodovotz, Timothy Billiar.
       SIGNIFICANCE: The immune-inflammatory responses that follow trauma contribute to clinical trajectory and patient outcomes. While remarkable advances have been made in trauma services and injury management, clarity on how the immune system in humans responds to trauma is lagging behind. Recent Advances : Multiplexing platforms have transformed our ability to analyze comprehensive immune mediator responses in human trauma. In parallel, with the establishment of large datasets, computational methods have been adapted to yield new insights based on mediator patterns. These efforts have added an important data layer to the emerging multi-omic characterization of the human response to injury.
    CRITICAL ISSUES: Outcome after trauma is greatly affected by the host immune-inflammatory response. Excessive or sustained responses can contribute to organ damage. Hence, understanding the pathophysiology behind traumatic injury is of vital importance.
    FUTURE DIRECTIONS: This review summarizes our work in the study of circulating immune mediators in trauma patients. Our foundational studies into mediator levels represent an important contribution to the concepts and computational challenges that these large datasets present. We hope to see further integration and understanding of multi-omics strategies in the field of trauma that can aid in patient endotyping and in potentially identifiying certain therapeutic targets in the future.
    DOI:  https://doi.org/10.1089/ars.2021.0054
  5. Am Surg. 2021 Apr 15. 31348211011098
    The History of Hemorrhagic Shock and Damage Control Resuscitation.
    David R Velez.
      The understanding and management of hemorrhagic shock have evolved significantly over the last 400 years. Injured patients in shock mandate immediate surgeon involvement. Every graduating surgical resident and every surgeon taking trauma call should thoroughly understand the concepts of damage control resuscitation and be prepared to care for these patients. This review seeks to revisit the history of hemorrhagic shock and the evolution of damage control resuscitation.
    Keywords:  acute care surgery; critical care; general surgery; trauma; trauma acute care
    DOI:  https://doi.org/10.1177/00031348211011098
  6. Ann Transl Med. 2021 Mar;9(5): 365
    Interleukin-28A maintains the intestinal epithelial barrier function through regulation of claudin-1.
    Liangzi Li, Chao Zhou, Teming Li, Weidong Xiao, Min Yu, Hua Yang.
       Background: Interleukin-28A (IL-28A or interferon-λ2) is reported to maintain intestinal mucosal homeostasis. However, the effects and mechanisms of IL-28A on intestinal ischemia reperfusion (I/R) have not yet been studied.
    Methods: Adult C57BL/6 mice were randomly divided into three groups: sham, I/R, and I/R+IL-28A (n=5 in each group). The I/R+IL-28A group mice were injected with recombinant mouse IL-28A 12 hours before the operation. Mice were sacrificed 6 hours after reperfusion. The mucosal permeability was investigated, and histology analyses were performed. Additionally, a hypoxic Caco-2 cell culture model was established. Fludarabine was used to inhibit phosphorylated signal transducer and activator of transcription 1 (pSTAT1). The expression of IL-28A, tight junctions (TJs), and pSTAT1 was assessed by western blot, immunohistochemical (IHC) staining, or immunofluorescence staining. Epithelial permeability was measured by transepithelial electrical resistance (TER).
    Results: The expression of IL-28A was decreased in intestinal lamina propria in the I/R group compared with the control group. Administration of IL-28A significantly alleviated the I/R-induced increase in intestinal permeability and tissue damage. Treatment with IL-28A significantly attenuated intestinal I/R-induced disruption of TJ proteins, including zonula occludens-1 (ZO-1), occludin, and claudin-1. In vitro, IL-28A treatment reversed the decrease in TER of Caco-2 monolayers exposed to hypoxic environments. IL-28A led to the activation of STAT1 and the upregulation of claudin-1 expression both in vivo and in vitro. Also, inhibiting phosphorylation of STAT1 reversed the effects of IL-28A on the expression and distribution of claudin-1 in Caco-2 cells.
    Conclusions: Intestinal epithelial barrier dysfunction caused by intestinal I/R is ameliorated by IL-28A via the regulation of claudin-1.
    Keywords:  I/R; IL-28A; STAT1; claudin-1; intestinal epithelial barrier
    DOI:  https://doi.org/10.21037/atm-20-5494
  7. Mil Med Res. 2021 Apr 12. 8(1): 25
    Chinese expert consensus on diagnosis and treatment of trauma-induced hypercoagulopathy.
    Chinese People’s Liberation Army Professional Committee of Critical Care Medicine and Chinese Society of Thrombosis, Hemostasis and Critical Care, Chinese Medicine Education Association
      Trauma-induced coagulopathy (TIC) is caused by post-traumatic tissue injury and manifests as hypercoagulability that leads to thromboembolism or hypocoagulability that leads to uncontrollable massive hemorrhage. Previous studies on TIC have mainly focused on hemorrhagic coagulopathy caused by the hypocoagulable phenotype of TIC, while recent studies have found that trauma-induced hypercoagulopathy can occur in as many as 22.2-85.1% of trauma patients, in whom it can increase the risk of thrombotic events and mortality by 2- to 4-fold. Therefore, the Chinese People's Liberation Army Professional Committee of Critical Care Medicine and the Chinese Society of Thrombosis, Hemostasis and Critical Care, Chinese Medicine Education Association jointly formulated this Chinese Expert Consensus comprising 15 recommendations for the definition, pathophysiological mechanism, assessment, prevention, and treatment of trauma-induced hypercoagulopathy.
    Keywords:  Coagulation dysfunction; Diagnosis; Thrombosis; Trauma; Treatment
    DOI:  https://doi.org/10.1186/s40779-021-00317-4
  8. Int J Crit Illn Inj Sci. 2020 Oct-Dec;10(4):10(4): 170-176
    Clinical implications of serum myoglobin in trauma patients: A retrospective study from a level 1 trauma center.
    Khalid Ahmed, Husham Abdelrahman, Ayman El-Menyar, Mahmoud Saqr, Ashwin D Silva, Sherif M Alkahky, Jowhara Al Qahtani, Ahammed Mekkodathil, Hassan Al-Thani, Ruben Peralta.
       Background: We aimed to study the clinical implication of high serum myoglobin levels in trauma patients.
    Methods: A retrospective analysis was conducted on data from trauma patients who were admitted to a level 1 trauma center between January 2012 and December 2015. A receiver operating characteristic (ROC) curve analysis was performed for the optimum myoglobin cutoff plotted against hospital length of stay of >1 week. Patients were divided into two groups (Group 1; low vs. Group 2; high myoglobin), and a comparative analysis was performed.
    Results: There were 898 patients who met the inclusion criteria with a mean age of 35.9 ± 14.6 years. Based on ROC, the myoglobin optimum cutoff was 1000 ng/ml (64% of patients were in Group 1 and 36% in Group 2). The mean myoglobin level was 328 ng/ml in patients with the Injury Severity Score (ISS) <15 versus 1202 ng/ml in patients with ISS ≥15 (P < 0.001). Patients in Group 2 had higher ISS (22.2 ± 10 vs. 18.8 ± 10), more musculoskeletal injuries (18.3% vs. 4.2%), more blood transfusion (74% vs. 39%), intubation (57% vs. 46.5%), and sepsis (12% vs. 7.3%). The length of hospital stays was significantly higher in Group 2, but mortality was comparable. High myoglobin levels had a crude odd ratio 2.41; 95% confidence interval (1.470-3.184) for a longer hospital stay with a positive predictive value of 89% and a specificity of 77%.
    Conclusions: One-third of the admitted trauma patients have elevated serum myoglobin level, which is associated with the prolonged hospital stay. The discriminatory power of myoglobin value of 1000 in trauma is fair, and further prospective assessments are needed.
    Keywords:  Hospital length of stay; injury; myoglobin; rhabdomyolysis; trauma
    DOI:  https://doi.org/10.4103/IJCIIS.IJCIIS_71_19
  9. Acta Anaesthesiol Scand. 2021 Apr 11.
    Supplemental oxygen therapy in trauma patients: an exploratory registry-based study.
    Mathias A Christensen, Jacob Steinmetz, George Velmahos, Lars S Rasmussen.
       BACKGROUND: Supplemental oxygen (SO) is one of the most commonly administered drugs in trauma patients and is recommended by guidelines. However, evidence supporting uniform administration is sparse, and excess oxygen use has been shown to be harmful in other patient populations. We hypothesized that SO may be harmful in patients with oxygen saturation>97%.
    METHODS: Patients with available information on SO-therapy in the American Trauma Quality Improvement Program 2017 database were included. Patients were categorized into three groups according to Emergency Department (ED) oxygen saturation: 1) Saturation<94%; 2) Saturation 94-97%; 3) Saturation 98-100%. Primary outcome was in-hospital mortality with comparisons made between patients who received SO or not. Secondary outcome was acute respiratory distress syndrome (ARDS). Patients were compared after propensity score matching.
    RESULTS: Overall, 864,340 patients were identified. Mean age was 47.4 ± 24.4 years and median injury severity score was 9. SO was associated with an increased risk of in-hospital mortality: (all patients: adjusted odds ratio (aOR) with 95% confidence interval (CI) 3.07 [2.92-3.22], ED saturation <94%: 2.63 [2.38-2.91], ED saturation 94%-97%: 2.71 [2.47-2.97], ED saturation >97%: 3.38 [3.16-3.61]. Same pattern was seen for in-hospital ARDS: (aOR 1.79, 95% CI [1.59-2.02], ED saturation <94%: aOR 1.75, 95% CI 1.37-2.24, ED saturation 94%-97%: aOR 1.81, 95% CI 1.43-2.29, ED saturation >97%: aOR 2.31, 95% CI 1.92-2.79).
    CONCLUSION: Based on propensity matched, registry data for trauma patients, the administration of SO was associated with a higher incidence of in-hospital mortality and ARDS. The highest risk was found in patients with an ED saturation >97%.
    Keywords:  ARDS; Trauma; mortality; oxygen therapy
    DOI:  https://doi.org/10.1111/aas.13829
  10. Immunobiology. 2021 Mar 27. pii: S0171-2985(21)00035-8. [Epub ahead of print]226(3): 152087
    Changes in extracellular cytokines in predicting disease severity and final clinical outcome of patients with blunt chest trauma.
    Minu Kumari, Purva Mathur, Richa Aggarwal, Karan Madan, Sushma Sagar, Amit Gupta, Surbhi Khurana, Vishnubhatla Sreenivas, Subodh Kumar.
       BACKGROUND: Chest trauma causes substantial morbidity and mortality and its severity is assessed using clinical diagnosis or scoring systems like Injury severity score (ISS) and thoracic trauma severity score (TTSS). Association of inflammatory cytokines with severity of disease and final clinical outcome is not clearly defined in patients with chest trauma. In this study, we thought to evaluate the inflammatory response in serum and bronchoalveolar lavage fluid (BALF) in chest trauma patients and correlate the level of extracellular cytokines with diseases severity and final outcome.
    METHODS: A total of 65 patients with blunt chest trauma and 30 healthy controls were enrolled in this prospective observational study. Assessment of inflammatory cytokines such as Interleukin (s) - IL-5, IL-13, IL-2, IL-6, IL-9, IL-1β, IFN-γ, TNF-α, IL-17A, IL-17F,IL-4, IL-21 and IL-22 was performed in both serum and bronchoalveolar lavage fluid using 13-plex multiplex kit using fluorescence-encoded bead based immunoassays.
    RESULTS: A significantly higher level of IL-13, IL-2, IL-6, IL-9, IL-1β, IFN-γ, TNF-α, IL-17A, IL-17F, IL-21 and IL-22 cytokines were observed in patients with blunt chest trauma compared to healthy controls. Level of IL-2, IL-6, IL-1β and IL-17A was significantly raised in the patients with blunt chest trauma who had a fatal outcome during the hospital stay. An elevated cytokine response of IL-13, IL-4, and IL-21 was noted in the group of patients with high (>5) thoracic trauma severity score.
    CONCLUSION: Routine monitoring of the inflammatory cytokine level in patients with chest trauma may be used routinely. Longer prospective studies should be encouraged to determine the role of cytokines in patients with chest trauma in predicting the patient final clinical outcome.
    Keywords:  Cytokines; Infection; Inflammation; Mortality; Sepsis; Trauma
    DOI:  https://doi.org/10.1016/j.imbio.2021.152087
  11. Asian J Surg. 2021 Apr 13. pii: S1015-9584(21)00181-0. [Epub ahead of print]
    A case-control study of risk factors for survival after laparotomy in patients with pancreatic trauma.
    Chao Yang, Xinyu Wang, Cuili Wu, Yongle Wang, Kai Wang, Weiwei Ding.
       BACKGROUND: Pancreatic trauma results in significant morbidity and mortality. However, few studies have investigated the postoperative prognostic factors in patients with pancreatic trauma.
    MATERIAL AND METHODS: A retrospective study was conducted on consecutive patients with pancreatic trauma who underwent surgery in a national referral trauma center. Clinical data were retrieved from the electronic medical system. Univariate and binary logistic regression analyses were performed to identify the perioperative clinical parameters that may predict the factors of mortality of the patients.
    RESULTS: A total of 150 patients underwent laparotomy due to pancreatic trauma during the study period. 128(85.4%) patients survived and 22 (14.6%) patients died due to pancreatic injury (10 patients died of recurrent intra-abdominal active hemorrhage and 12 died of multiple organ failure). Univariate analysis showed that age, hemodynamic status, and injury severe score (ISS) as well as postoperative serum levels of C-reactive protein (CRP), procalcitonin, albumin, creatinine and the volume of intraoperative blood transfusion remained strongly predictive of mortality (P < 0.05). Binary logistic regression analysis showed that the independent risk factors for prognosis after pancreatic trauma were age (P = 0.010), preoperative hemodynamic instability (P = 0.015), postoperative CRP ≥154 mg/L (P = 0.014), and postoperative serum creatinine ≥177 μmol/L (P = 0.027).
    CONCLUSIONS: In this single-center retrospective study, we demonstrated that preoperative hemodynamic instability, severe postoperative inflammation (CRP ≥154 mg/L) and acute renal failure (creatinine ≥177 μmol/L) were associated with a significant risk of mortality after pancreatic trauma.
    Keywords:  Logistic regression analysis; Pancreatic trauma; Prognosis; Risk factor
    DOI:  https://doi.org/10.1016/j.asjsur.2021.03.032
  12. Stroke. 2021 Apr 12. STROKEAHA120032196
    Divergent Functions of Tissue-Resident and Blood-Derived Macrophages in the Hemorrhagic Brain.
    Che-Feng Chang, Brittany A Goods, Michael H Askenase, Hannah E Beatty, Artem Osherov, Jonathan H DeLong, Matthew D Hammond, Jordan Massey, Margaret Landreneau, J Christopher Love, Lauren H Sansing.
       BACKGROUND AND PURPOSE: Brain tissue-resident microglia and monocyte-derived macrophages (MDMs) are innate immune cells that contribute to the inflammatory response, phagocytosis of debris, and tissue repair after injury. We have previously reported that both microglia and MDMs transition from proinflammatory to reparative phenotypes over days after an intracerebral hemorrhage (ICH). However, their individual functional properties in the brain remain largely unknown. Here we characterized the differences between microglia and MDMs and further elucidate their distinct activation states and functional contributions to the pathophysiology and recovery after ICH.
    METHODS: Autologous blood injection was used to model ICH in mice. Longitudinal transcriptomic analyses on isolated microglia and MDMs from mice at days 1, 3, 7 and 10 after ICH and naive controls identified core transcriptional programs that distinguish these cells. Imaging flow cytometry and in vivo phagocytosis assays were used to study phagocytic ability of microglia and MDMs. Antigen presentation was evaluated by ovalbumin-OTII CD4 T-cell proliferation assays with bone marrow-derived macrophages and primary microglia cultures.
    RESULTS: MDMs had higher phagocytic activity and higher erythrophagocytosis in the ICH brain. Differential gene expression revealed distinct transcriptional signatures in the MDMs and microglia after ICH. MDMs had higher expression of MHCII (major histocompatibility complex class II) genes than microglia at all time points and greater ability to induce antigen-specific T-cell proliferation.
    CONCLUSIONS: The different ontogeny of microglia and MDMs lead to divergent responses and functions in the inflamed brain as these 2 cell populations differ in phagocytic functions and antigen-presenting capabilities in the brain after ICH.
    Keywords:  cerebral hemorrhage; immunity, innate; macrophages; microglia; phagocytosis
    DOI:  https://doi.org/10.1161/STROKEAHA.120.032196
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