Sex differences in the effects of mild traumatic brain injury and progesterone treatment on anxiety-like behavior and fear conditioning in rats.

Mild traumatic brain injuries (mild TBIs) commonly occur in young adults of both sexes, oftentimes in high-stress environments. In humans, sex differences have been observed in the development of post-concussive anxiety and PTSD-like behaviors. Progesterone, a sex steroid that has neuroprotective properties, restores cognitive function in animal models following more severe TBI, but its effectiveness in preventing the psychological symptoms associated with mild TBI has not been evaluated. Using a model of mild TBI that pairs a social stressor (social defeat) with weight drop, male and naturally estrous-cycling female rats were treated with 4 mg/kg progesterone or vehicle once daily for 5 days after injury. Behavioral measures, including elevated plus maze (EPM), contextual fear conditioning, and novel object recognition (NOR) were assessed following progesterone treatment. Anxiety-like behavior was increased by mild TBI in male rats, with a smaller effect seen in female rats in the diestrus phase at the time of EPM testing. In contrast, mild TBI impaired fear learning in female rats in estrus at the time of fear acquisition. Progesterone treatment failed to attenuate post-mild TBI anxiety-like behavior in either sex. Furthermore, progesterone increased fear conditioning and impaired NOR discrimination in male rats, independent of TBI status. Overall, both sex and estrous cycle contributed to psychological outcomes following mild TBI, which were not ameliorated by post-TBI progesterone. This suggests sex steroids play an important role as a moderator of the expression of mild TBI-induced psychological symptoms, rather than as a potential treatment for their underlying etiology.

Disparities in Outcomes During Lower Respiratory Tract Infection in American Indian Children: A 9-Year Retrospective Analysis in a Rural Population in South Dakota.

BACKGROUND: American Indian (AI) children are at increased risk for severe disease during lower respiratory tract infection (LRTI). The reasons for this increased severity are poorly understood. The objective of this study was to define the clinical presentations of LRTI and highlight the differences between AI and non-AI previously healthy patients under the age of 24 months. METHODS: We performed a retrospective chart review between October 2010 and December 2019. We reviewed 1245 patient charts and 691 children met inclusion criteria for this study. Data records included demographics, clinical, laboratory data, and illness outcomes. RESULTS: Of 691 patients, 120 were AI and 571 were non-AI. There was a significant difference in breast-feeding history (10% of AI vs. 28% of non-AI, P < 0.0001) and in secondhand smoke exposure (37% of AI vs. 21% of non-AI, P < 0.0001). AI children had increased length of hospitalization compared with non-AI children (median of 3 vs. 2 days, P < 0.001). In addition, AI children had higher rates of pediatric intensive unit admission (30%, n = 37) compared with non-AI children (11%; n = 67, P < 0.01). AI children also had higher rates (62.5%, n = 75) and duration of oxygen supplementation (median 3 days) than non-AI children (48%, n = 274, P = 0.004; median 2 days, P = 0.0002). On a multivariate analysis, AI race was an independent predictor of severe disease during LRTI. CONCLUSIONS: AI children have increased disease severity during LRTI with longer duration of hospitalization and oxygen supplementation, a higher rate of oxygen requirement and Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation pediatric intensive care unit admissions, and a greater need for mechanical ventilation. These results emphasize the need for improvement in health policies and access to health care in this vulnerable population.

Central Administration of Cyclosporine A Decreases Ethanol Drinking.

AIMS: Abstinence among alcohol dependent liver graft recipients is remarkably high. The routine use of anti-immune agents in these patients led to rodent studies showing that immunosuppressants acting through inhibition of calcineurin (CLN) are highly effective in decreasing alcohol consumption. It remained unclear, however, whether the decreased alcohol consumption in rodent models is mediated through peripheral suppression of immune response or centrally through direct inhibition of cyclophilin-CLN in the brain. We tested the hypothesis that direct brain inhibition of CLN with intracerebroventricular (ICV) injections of the immunosuppressant cyclosporine A (CsA) is sufficient to decrease ethanol consumption in a rodent model of binge-like drinking. METHODS: Male C57BL/6NHsd mice were put through a modified 'drinking in the dark' (DID) paradigm. Effects of both peripheral (IP) and central (ICV) injections of CsA on ethanol consumption were assessed. RESULTS: Here, as in earlier work, IP CsA administration significantly decreased alcohol consumption. Supporting our hypothesis, central administration of CsA was sufficient to decrease alcohol consumption in a dose-dependent manner. There was no significant effect of CsA on water or sucrose consumption. CONCLUSIONS: These results clearly implicate a CLN-mediated mechanism in brain in the inhibitory effects of CsA on ethanol consumption and provide novel targets for investigation of treatment for Alcohol Use Disorders (AUD). These results also add to the growing body of literature implicating neuroimmune mechanisms in the etiology, pathophysiology and behaviors driving AUD. SHORT SUMMARY: The unusually high abstinence rate and routine use of immunosuppressants in AUD liver graft recipients led us to rodent studies showing that immunosuppressants acting through inhibition of calcineurin (CLN) are highly effective in decreasing drinking. Here we demonstrate that this effect is mediated by brain rather than peripheral immune mechanisms.