A method for the selective depletion of microglia in the dorsal hippocampus in the juvenile rat brain.

BACKGROUND: To understand the role of microglia in brain function and development, methods have emerged to deplete microglia throughout the brain. Liposome-encapsulated clodronate (LEC) can be infused into the brain to deplete microglia in a brain-region and time-specific manner. NEW METHOD: This study validates methodology to deplete microglia in the rat dorsal hippocampus (dHP) during a specific period of juvenile development. Stereotaxic surgery was performed to infuse LEC at postnatal day (P) 16 or 19 into dHP. Rat brains were harvested at various ages to determine specificity of infusion and duration of depletion. RESULTS: P19 infusion of LEC into dHP with a 27G syringe depleted microglia in dHP subregions CA1, dentate gyrus (DG), and CA3 from P24-P30. There was also evidence of depletion in parietal cortex above the infusion site. P16 infusion of LEC with a 32 G syringe depleted microglia only in dHP subregions CA1 and DG from P21-P40. COMPARISON WITH EXISTING METHOD(S): Previous methods have infused LEC intra-hippocampally in adult rats or intra-cerebroventricularly in neonatal rats. This study is the first to publish methodology to deplete microglia in a brain-region specific manner during juvenile rat development. CONCLUSIONS: The timing of LEC infusion during the juvenile period can be adjusted to achieve maximal microglia depletion by a specific postnatal day. A 27G needle results in LEC backflow during the infusion, but also allows LEC to reach all subregions of dHP. Infusion with a 32 G needle prevents backflow during infusion, but results in a more local spread of LEC within dHP.

An Examination of the Long-Term Neurodevelopmental Impact of Prenatal Zika Virus Infection in a Rat Model Using a High Resolution, Longitudinal MRI Approach.

Since Zika virus (ZIKV) first emerged as a public health concern in 2015, our ability to identify and track the long-term neurological sequelae of prenatal Zika virus (ZIKV) infection in humans has been limited. Our lab has developed a rat model of maternal ZIKV infection with associated vertical transmission to the fetus that results in significant brain malformations in the neonatal offspring. Here, we use this model in conjunction with longitudinal magnetic resonance imaging (MRI) to expand our understanding of the long-term neurological consequences of prenatal ZIKV infection in order to identify characteristic neurodevelopmental changes and track them across time. We exploited both manual and automated atlas-based segmentation of MR images in order to identify long-term structural changes within the developing rat brain following inoculation. The paradigm involved scanning three cohorts of male and female rats that were prenatally inoculated with 107 PFU ZIKV, 107 UV-inactivated ZIKV (iZIKV), or diluent medium (mock), at 4 different postnatal day (P) age points: P2, P16, P24, and P60. Analysis of tracked brain structures revealed significantly altered development in both the ZIKV and iZIKV rats. Moreover, we demonstrate that prenatal ZIKV infection alters the growth of brain regions throughout the neonatal and juvenile ages. Our findings also suggest that maternal immune activation caused by inactive viral proteins may play a role in altered brain growth throughout development. For the very first time, we introduce manual and automated atlas-based segmentation of neonatal and juvenile rat brains longitudinally. Experimental results demonstrate the effectiveness of our novel approach for detecting significant changes in neurodevelopment in models of early-life infections.

Selective Atrophy of the Vastus Medialis: Does It Exist in Women With Nontraumatic Patellofemoral Pain?

BACKGROUND: A commonly cited theory related to the pathomechanics of patellofemoral pain (PFP) states that atrophy of the vastus medialis (VM) muscle leads to lateral tracking of the patella. However, isolated atrophy of the VM or atrophy of the quadriceps muscle group as a whole, has not been consistently reported in this population. PURPOSE: To compare individual and total quadriceps muscle volumes between women with nontraumatic PFP and women without PFP as measured on magnetic resonance imaging scans. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 52 women with nontraumatic PFP and 64 women without PFP between the ages of 18 and 45 years participated. Magnetic resonance imaging scans of the thigh were obtained from the anterior inferior iliac spine to the tibial plateau. Individual quadriceps muscle cross-sectional area measurements were obtained from each image, and muscle volumes for the VM, vastus lateralis, vastus intermedius, and rectus femoris were calculated. Muscle volume measurements were expressed in absolute values and normalized to body mass. Separate 2-way mixed-factorial analysis of variance (group × muscle) were used to compare absolute and normalized individual muscle volumes between groups. Independent t tests were used to compare absolute and normalized total quadriceps volumes between groups. RESULTS: There was no difference in absolute and normalized individual muscle volumes between individuals with and those without PFP. Additionally, absolute and normalized total muscle volumes did not differ between groups. CONCLUSION: Our findings do not support the concept of preferential atrophy of the VM or generalized quadriceps atrophy in women with nontraumatic PFP.

An IL-6 receptor antagonist attenuates postpartum anhedonia, but has no effect on anhedonia precipitated by subchronic stress in female rats.

RATIONALE: Nearly 60-80% of women experience some form of sadness, anxiety, or anhedonia in the weeks following the birth of a child (Patel et al. 23(2):534-42, 2012; Degner 10: 359;j4692, 2017); however, the exact mechanisms that precipitate these changes in mood postpartum are still unknown. It is well-known that the function of the peripheral immune system is significantly altered during pregnancy in order to protect the developing fetus from being rejected by the maternal immune system (Fallon et al. 17(1):7-17, 2002), and we have recently found a dramatic change in the central immune system during and just after pregnancy in female rats (Sherer et al. 66:201-209, 2017). We observed anhedonia in Sprague-Dawley rat dams on the day of birth that is associated with an increase in interleukin (IL)-6 expression in the brain on the day of birth (Posillico and Schwarz 298(Pt B):218-28, 2016). OBJECTIVES: The goal of the current experiments was to determine whether inhibiting the IL-6 receptor could prevent onset of this postpartum anhedonia, or anhedonia precipitated by subchronic stress in non-pregnant females. RESULTS: Treatment with an IL-6 receptor antibody attenuated postpartum anhedonia as characterized by a decrease in sucrose preference. In contrast, this antibody had no effect on the decrease in sucrose preference induced following a week of forced swim stress in non-pregnant female rats. CONCLUSIONS: The results of these studies suggest that the molecular mechanisms that underlie the onset of anhedonia following birth or mild stress in female rats may be distinct.

Mercury Concentrations in Feathers of Adult and Nestling Osprey (Pandion haliaetus) from Coastal and Freshwater Environments of Florida.

We determined mercury (Hg) concentrations in feathers of osprey (Pandion haliaetus), both nestlings (n = 95) and adults (n = 110), across peninsular Florida and the Florida Keys during February-August 2014. Feathers plucked from nestlings, aged 3-7 weeks, contained Hg concentrations that ranged from 0.338 to 45.79 mg/kg and averaged 6.92 ± 7.58 mg/kg (mean ± 1SD). Feathers shed from adults contained significantly higher concentrations ranging from 0.375 to 93.65 mg/kg, with an average of 17.8 ± 16.1 mg/kg. These levels were in the upper range of previously reported feather Hg concentrations of osprey and clearly show that Florida continues to have Hg hotspots that are elevated compared with many other regions. While these concentrations did not exceed levels previously reported in osprey from heavily Hg contaminated areas that showed no evidence of reproductive impairments, we cannot rule out potential individual-level effects to highly exposed nestlings after fledging. Mercury concentrations in nestlings were highest in coastal habitats of Collier and Monroe counties, where ongoing declines in osprey populations also have been documented.

Fixation of supracondylar femoral fractures following total knee arthroplasty: is there any difference comparing angular stable plate fixation versus rigid interlocking nail fixation?

INTRODUCTION: Literature does not provide any reliable comparison between angular stable plate fixation and rigid nail fixation for stabilization of supracondylar periprosthetic femoral fractures. Thus, the purpose of this study was to compare these two implants in clinical practice relating to fracture healing, functional results and treatment-related complications. PATIENTS AND METHODS: In this retrospective study (level IV), clinical and radiographic records of 86 patients (62 female and 24 male, average age: 75.6) with supracondylar periprosthetic femoral fractures between 1996 and 2010 were analyzed. 48 patients underwent lateral plate fixation by an angular stable plate system (LISS), whereas 38 patients were stabilized by a rigid interlocking nail device. RESULTS: Sixty-four (76 %) patients returned to their pre-injury activity level and were satisfied with their clinical outcome. We had an overall Oxford outcome score of 2.21, with patients following angular stable plate fixation of 2.22, and patients after rigid nail fixation of 2.20. Successful fracture healing within 6 months was achieved in 74 (88 %) patients. Comparing between plate fixation and nail fixation, statistical analysis did not reveal any significant differences. Overall, we had a relatively high rate of fracture healing and a satisfactory functional outcome with both implants. Both methods of fixation showed similar results relating to the functional outcome and individual satisfaction of the patients. However, with regards to fracture healing and treatment-related complications, intramedullary nail fixation showed slight advantages.

Mild executive dysfunctions in undergraduates are related to recollecting words never presented.

The aim of this study was to explore whether individual differences in executive function in undergraduate students (n = 72) contribute to false recall and recognition as obtained with the Deese/Roediger-McDermott (DRM) paradigm. Participants were subjected to the DRM paradigm and also were given a test designed to assess executive function--the Random Number Generation task (RNG). A relationship was found between heightened seriation on the RNG (indicating a deficiency in the ability to inhibit cognitive schemes) and false recognition of non-presented, critical lure words in the DRM paradigm. This suggests that individual differences in executive function do occur in a healthy population and that the reconstructive activity inherent in memory depends in part on executive functioning.