Phenotypic characterization of frontal cortex microglia in a rat model of post-traumatic stress disorder.

INTRODUCTION: Post-traumatic stress disorder (PTSD) is an anxiety disorder induced by psychologically traumatic events. Using a rat model, this study aimed to determine whether psychological trauma alters relative expression between pro-inflammatory and anti-inflammatory markers in microglia. To meet this goal, expression of genes encoding i-NOS, arginase, TNF-α, interleukin-10, CD74, and Mannose Receptor C was analyzed on multiple days following trauma exposure. METHODS: Single-prolonged stress (SPS) was used to model PTSD in male Sprague-Dawley rats. Twenty-four rats (12 Controls and 12 SPS-exposed) were sacrificed on Days 1, 3, and 7 post-SPS. Twenty-four (12 Controls and 12 SPS-exposed) additional rats were exposed to classical fear conditioning on Day 7, and fear extinction on Days 8, 9, 10, 15, 16, and 17. Freezing behavior was measured to assess fear resolution. Microglial isolates were collected from the frontal cortex, and RNA was extracted. Changes in relative expression of target genes were quantified via RT-PCR. RESULTS: SPS rats showed significant decreases in IL-10 and TNF-α expression and increases in the i-NOS:Arginase and TNF-α:IL-10 ratios compared to Controls on Day 1, but not on Day 3 or Day 7 for any of the dependent variables. Day 17 SPS rats showed a significant decrease in IL-10 expression and an increase in the TNF-α:IL-10 ratio, further characterized by a significant inverse relationship between IL-10 expression and fear persistence. CONCLUSION: Psychological trauma impacts the immunological phenotype of microglia of the frontal cortex. Consequently, future studies should further evaluate the mechanistic role of microglia in PTSD pathology.

Predicting military working dog core temperature during exertional heat strain: Validation of a Canine Thermal Model.

Military working dogs (MWDs) operate under a wide range of conditions, including hot environments. Predicting how long a MWD can safely work without overheating is important for both health and performance. A Canine Thermal Model (CTM) was developed to predict core temperature (Tc) of MWDs. The CTM calculates heat storage from the balance of heat production from metabolism and heat exchange with the environment. Inputs to the CTM are: meteorological conditions (ambient temperature, relative humidity, solar radiation and wind speed), physical characteristics of the dog (mass, length), and metabolic activity (MET level, estimated from accelerometer data). The CTM was validated against Tc measured in 23 MWDs during training sessions (11.6 ± 5.0 min (mean ± standard deviation), range 4-26 min) in October (24 °C, 52% RH), March (14 °C, 74% RH), or August (28 °C, 64% RH), and 24 kennel MWDs during a standard exercise walk (11.4 ± 3.3 min, range 5.6-18 min) in July (26 °C, 77% RH). The CTM was considered acceptable if predicted Tc was within ±0.5 °C of measured Tc at the end of exercise. Compared to Tc at the end of training sessions (39.8 ± 0.6 °C, range 38.4-41.1 °C) and exercise walks (40.0 ± 0.7 °C, range 38.9-41.4 °C), the CTM-predicted Tc was within ±0.5 °C for 71 of 84 cases (85%) and 19 of 24 cases (79%), respectively. The mean difference between CTM-predicted and measured final Tc during training was -0.04 ± 0.43 °C, with 80 of 84 cases (95%) within the range of ±2 SD (Bland Altman comparison). During exercise walks the mean difference was -0.15 °C ± 0.57, with 23 of 24 cases (96%) within ±2 SD. These results support the use of the CTM to predict Tc of MWDs for the types of physical activities described above.

Core temperature responses of military working dogs during training activities and exercise walks.

Heat strain is common in military working dogs (MWDs), but can be mitigated by limiting duration of activity to avoid overheating and allowing sufficient time for recovery. To determine work/rest times for MWDs, temperature responses during training must be characterized. This study measured body core temperature of 48 MWDs at Lackland Air Force Base, San Antonio, TX. Twenty-four MWDs in training for patrol and detection activities participated under a range of ambient temperatures in August (27°C-32°C), October (22°C-26°C) and March (approximately 13°C). These MWDs swallowed a telemetric thermometer pill to measure continuous gastrointestinal tract temperature (Tgi). Twenty-four kennel MWDs participated in July (25°C-29°C). In these dogs rectal temperature (Tre) was measured manually during a standard exercise walk. For the MWDs in training, Tgi before the first activity was 38.5±0.5°C (mean±SD) and final Tgi was 39.8±0.6°C after sessions that lasted 13.1±4.9 minutes (5.4 to 26.3 minutes). Peak Tgi, 0.4±0.4°C above final Tgi, occurred 8 to 12 minutes into recovery. Before beginning a second activity 40 to 165 minutes later, Tgi was within 0.5°C of initial values for 80% of dogs. For the kennel MWDs, Tre was 39.0±0.8°C (37.7°C to 40.7°C) at the start and 40.1±0.6°C at the end of the 21.3±2.8 minute walk. The continuous increase in core temperature during activity of both groups of MWDs indicates that limiting exercise duration is important for minimizing risk of overheating in MWDs. The observation of continued increase in Tgi to a peak after exercise ends suggests that for MWDs suspected of overheating temperature should be monitored for at least 15 minutes postexercise to ensure recovery.