ABSTRACT
Exposure to adversity and traumatic events affects well-being across important domains of functioning, including mental, physical, social, emotional, spiritual, and neurobiological. Situated as a focal point throughout neighborhoods, recreation centers are a prime opportunity to cultivate spaces of safety and healing. However, current models of trauma-informed care largely do not map neatly onto the recreation organizational structure and functioning. This paper describes the efforts over the past five years to transform the City of Cleveland, Ohio's 22 recreation centers into trauma-informed Neighborhood Resource and Recreation Centers (NRRCs)--places where children, youth, and adults can readily acquire the support and services they need in an environment in which trauma-informed care principles are fully embedded in the fabric of the organization's culture. Phase 1 included transitioning the recreation centers to NRRCs, hiring of trained social workers and counselors to work within the recreation centers, and training all recreation staff about trauma. Phase 2 included development of NRRC trauma-informed standards, development of the Trauma-Informed Progress Tool to track change over time, development of Trauma-Informed Leadership Competencies for Center Managers, and ongoing training for the social workers and counselors. We discuss ideas for future work and lessons learned from each phase.
ABSTRACT
Sepsis is a complex syndrome characterized by organ dysfunction and a dysregulated immune host response to infection. There is currently no effective treatment for sepsis, but platelets have been proposed as a potential therapeutic target for the treatment of sepsis. We hypothesized that the NLRP3 inflammasome is activated in platelets during sepsis and may be associated with multiorgan injury in response to polymicrobial sepsis. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in 12- to 13-week-old male Sprague-Dawley rats. The necrotic cecum was removed at 24 h post-CLP. At 72 h post-CLP, activated platelets were significantly increased in CLP versus Sham rats. Colocalization of NLRP3 inflammasome components was observed in platelets from CLP rats at 72 h post-CLP. Plasma, pulmonary, and renal levels of IL-1ß and IL-18 were significantly higher in CLP rats compared to Sham controls. Soluble markers of endothelial permeability were increased in CLP versus Sham. Renal and pulmonary histopathology were markedly elevated in CLP rats compared to Sham controls. NLRP3 is activated in platelets in response to CLP and is associated with inflammation, endothelial permeability and multiorgan injury. Our results indicate that activated platelets may play a role to cause multiorgan injury in sepsis and may have therapeutic potential for the treatment of sepsis multiorgan injury.
Subject(s)
Blood Platelets/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/blood , Sepsis/blood , Animals , Capillary Permeability/physiology , Caspase 1/blood , Cecum/surgery , Cells, Cultured , Endothelium, Vascular/physiology , Interleukin-18/metabolism , Interleukin-1beta/metabolism , Kidney/metabolism , Ligation , Lipopolysaccharides/pharmacology , Lung/metabolism , Male , Multiple Organ Failure/etiology , Multiple Organ Failure/metabolism , Multiple Organ Failure/physiopathology , NLR Family, Pyrin Domain-Containing 3 Protein/physiology , Platelet Activation/drug effects , Platelet Activation/physiology , Rats, Sprague-Dawley , Sepsis/complications , Sepsis/physiopathologyABSTRACT
Previous studies have demonstrated that T-helper 17 (TH17) cells and cytolytic natural killer (cNK) cells are increased in women with preeclampsia. In this study we investigated the role of placental ischemia-stimulated TH17 cells in induction of cNK cells in pregnancy. We further assessed the role of TH17 cell-mediated oxidative stress in facilitation of cNK cell activation in pregnancy by treating rats with the SOD mimetic tempol. CD4+/CD25- cells were isolated from reduced uterine perfusion pressure (RUPP) rats and differentiated into TH17 cells in vitro. On day 12 of gestation ( GD12), 1 × 106 placental ischemia-stimulated TH17 cells were injected into normal pregnant (NP) rats (NP + RUPP TH17 rats), and a subset of rats were treated with tempol (30 mg·kg-1·day-1) from GD12 to GD19 (NP + RUPP TH17 + tempol rats). On GD19, cNK cells, mean arterial pressure, fetal weight, and cNK cell-associated cytokines and proteins were measured. Placental cNK cells were 2.9 ± 1, 14.9 ± 4, and 2.8 ± 1.0% gated in NP, NP + RUPP TH17, and NP + RUPP TH17 + tempol rats, respectively. Mean arterial pressure increased from 96 ± 5 mmHg in NP rats to 118 ± 2 mmHg in NP + RUPP TH17 rats and was 102 ± 3 mmHg in NP + RUPP TH17 + tempol rats. Fetal weight was 2.37 ± 0.04, 1.95 ± 0.14, and 2.3 ± 0.05 g in NP, NP + RUPP TH17, and NP + RUPP TH17 + tempol rats, respectively. Placental IFNγ increased from 1.1 ± 0.6 pg/mg in NP rats to 3.9 ± 0.6 pg/mg in NP + RUPP TH17 rats. Placental perforin increased from 0.18 ± 0.18 pg/mg in NP rats to 2.4 ± 0.6 pg/mg in NP + RUPP TH17 rats. Placental levels of granzymes A and B followed a similar pattern. Treatment with tempol did not lower placental cNK cytokines or proteins. The results of the present study identify TH17 cells as a mediator of aberrant NK cell activation that is associated with preeclampsia.
