PET imaging of microglia using PBR28suv determines therapeutic efficacy of autologous bone marrow mononuclear cells therapy in traumatic brain injury.

Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of rats: Sham, CCI-alone and CCI-BMMNCs (AUTO). One hundred twenty days after injury, rodents were imaged with PBR28 and their cognitive behavior assessed utilizing the Morris Water Maze. Subsequent ex vivo analysis included brain volume and immunohistochemistry. BMMNCs therapy attenuated PBR28suv in comparison to CCI alone and it improved spatial learning as measured by the Morris Water Maze. Ex vivo analysis demonstrated preservation of brain volume, a decrease in amoeboid-shaped microglia in the dentate gyrus and an increase in the ratio of ramified to amoeboid microglia in the thalamus. PBR28suv is a viable option to measure efficacy of BMMNCs therapy after TBI.

PET Imaging of Peripheral Benzodiazepine Receptor Standard Uptake Value Increases After Controlled Cortical Impact, a Rodent Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a chronic, life threatening injury for which few effective interventions are available. Evidence in animal models suggests un-checked immune activation may contribute to the pathophysiology. Changes in regional density of active brain microglia can be quantified in vivo with positron emission topography (PET) with the relatively selective radiotracer, peripheral benzodiazepine receptor 28 (11 C-PBR28). Phenotypic assessment (activated vs resting) can subsequently be assessed (ex vivo) using morphological techniques. To elucidate the mechanistic contribution of immune cells in due to TBI, we employed a hybrid approach involving both in vivo (11 C-PBR28 PET) and ex vivo (morphology) to elucidate the role of immune cells in a controlled cortical impact (CCI), a rodent model for TBI. Density of activated brain microglia/macrophages was quantified 120 hours after injury using the standardized uptake value (SUV) approach. Ex vivo morphological analysis from specific brain regions using IBA-1 antibodies differentiated ramified (resting) from amoeboid (activated) immune cells. Additional immunostaining of PBRs facilitated co-localization of PBRs with IBA-1 staining to further validate PET data. Injured animals displayed greater PBR28suv when compared to sham animals. Immunohistochemistry demonstrated elevated density of amoeboid microglia/macrophages in the ipsilateral dentate gyrus, corpus callosum, thalami and injury penumbra of injured animals compared to sham animals. PBR co-stained with amoeboid microglia/macrophages in the injury penumbra and not with astrocytes. These data suggest the technologies evaluated may serve as bio-signatures of neuroinflammation following severe brain injury in small animals, potentially enabling in vivo tracking of neuroinflammation following TBI and cellular-based therapies.

Impact of Hurricane Harvey on Healthcare Utilization and Emergency Department Operations.

INTRODUCTION: Hurricanes have increased in severity over the past 35 years, and climate change has led to an increased frequency of catastrophic flooding. The impact of floods on emergency department (ED) operations and patient health has not been well studied. We sought to detail challenges and lessons learned from the severe weather event caused by Hurricane Harvey in Houston, Texas, in August 2017. METHODS: This report combines narrative data from interviews with retrospective data on patient volumes, mode of arrival, and ED lengths of stay (LOS). We compared the five-week peri-storm period for the 2017 hurricane to similar periods in 2015 and 2016. RESULTS: For five days, flooding limited access to the hospital, with a consequent negative impact on provider staffing availability, disposition and transfer processes, and resource consumption. Interruption of patient transfer capabilities threatened patient safety, but flexibility of operations prevented poor outcomes. The total ED patient census for the study period decreased in 2017 (7062 patients) compared to 2015 (7665 patients) and 2016 (7770) patients). Over the five-week study period, the arrival-by-ambulance rate was 12.45% in 2017 compared to 10.1% in 2016 (p < 0.0001) and 13.7% in 2015 (p < 0.0001). The median ED length of stay (LOS) in minutes for admitted patients was 976 minutes in 2015 (p < 0.0001) compared to 723 minutes in 2016 and 591 in 2017 (p < 0.0001). For discharged patients, median ED LOS was 336 minutes in 2016 compared to 356 in 2015 (p < 0.0001) and 261 in 2017 (p < 0.0001). Median boarding time for admitted ED patients was 284 minutes in 2016 compared to 470 in 2015 (p < 0.0001) and 234.5 in 2017 (p < 0.001). Water damage resulted in a loss of 133 of 179 inpatient beds (74%). Rapid and dynamic ED process changes were made to share ED beds with admitted patients and to maximize transfers post-flooding to decrease ED boarding times. CONCLUSION: A number of pre-storm preparations could have allowed for smoother and safer ride-out functioning for both hospital personnel and patients. These measures include surplus provisioning of staff and supplies to account for limited facility access. During a disaster, innovative flexibility of both ED and hospital operations may be critical when disposition and transfer capibilities or bedding capacity are compromised.