Medial prefrontal cortex to nucleus reuniens circuit is critical for performance in an operant delayed nonmatch to position task.

Working memory refers to the temporary retention of a small amount of information used in the execution of a cognitive task. The prefrontal cortex and its connections with thalamic subregions are thought to mediate specific aspects of working memory, including engaging with the hippocampus to mediate memory retrieval. We used an operant delayed-non match to position task, which does not require the hippocampus, to determine roles of the rodent medial prefrontal cortex (mPFC), the nucleus reuniens thalamic region (RE), and their connection.

Transient strain differences in an operant delayed non-match to position task.

Working memory refers to the temporary retention of a small amount of information used in the execution of a cognitive task. Working memory impairments are one of the common hallmarks of many neuropsychiatric and neurological disorders including schizophrenia and Alzheimer's disease. Here, we investigated Fischer 344 and Long-Evans rats for strain and sex differences in working memory using the operant-based DNMTP task.

Impaired neural differentiation and glymphatic CSF flow in the rat model of neonatal hydrocephalus: genetic interaction with .

Neonatal hydrocephalus affects about one child per 1000 births and is a major congenital brain abnormality. We previously discovered a gene mutation within the coiled-coil domain-containing 39 () gene, which causes the () phenotype in mice due to lack of ependymal-cilia-mediated cerebrospinal fluid (CSF) flow. In this study, we used CRISPR/Cas9 to introduce the gene mutation into rats, which are more suitable for imaging and surgical experiments.

Magnetic resonance imaging of disease progression and resolution in a transgenic mouse model of pulmonary fibrosis.

Pulmonary fibrosis contributes to morbidity and mortality in a range of diseases, and there are no approved therapies for reversing its progression. To understand the mechanisms underlying pulmonary fibrosis and assess potential therapies, mouse models are central to basic and translational research. Unfortunately, metrics commonly used to assess murine pulmonary fibrosis require animals to be grouped and euthanized, increasing experimental difficulty and cost.

Blocking lymphocyte trafficking with FTY720 prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns.

Intrauterine infection (chorioamnionitis) aggravates neonatal hypoxic-ischemic (HI) brain injury, but the mechanisms linking systemic inflammation to the CNS damage remain uncertain. Here we report evidence for brain influx of T-helper 17 (TH17)-like lymphocytes to coordinate neuroinflammatory responses in lipopolysaccharide (LPS)-sensitized HI injury in neonates. We found that both infants with histological chorioamnionitis and rat pups challenged by LPS/HI have elevated expression of the interleukin-23 (IL-23) receptor, a marker of early TH17 lymphocytes, in the peripheral blood mononuclear cells.

The effectiveness of sit-stand workstations for changing office workers' sitting time: results from the Stand@Work randomized controlled trial pilot.

Background: Prolonged sitting time is detrimental for health. Individuals with desk-based occupations tend to sit a great deal and sit-stand workstations have been identified as a potential strategy to reduce sitting time. Hence, the objective of the current study was to examine the effects of using sit-stand workstations on office workers' sitting time at work and over the whole day.

Desk-based workers' perspectives on using sit-stand workstations: a qualitative analysis of the Stand@Work study.

Background: Prolonged sitting time has been identified as a health risk factor. Sit-stand workstations allow desk workers to alternate between sitting and standing throughout the working day, but not much is known about their acceptability and feasibility. Hence, the aim of this study was to qualitatively evaluate the acceptability, feasibility and perceptions of using sit-stand workstations in a group of desk-based office workers.

Synergy of combined tPA-edaravone therapy in experimental thrombotic stroke.

Edaravone, a potent antioxidant, may improve thrombolytic therapy because it benefits ischemic stroke patients on its own and mitigates adverse effects of tissue plasminogen activator (tPA) in preclinical models. However, whether the combined tPA-edaravone therapy is more effective in reducing infarct size than singular treatment is uncertain. Here we investigated this issue using a transient hypoxia-ischemia (tHI)-induced thrombotic stroke model, in which adult C57BL/6 mice were subjected to reversible ligation of the unilateral common carotid artery plus inhalation of 7.

Intranasal delivery of cell-penetrating anti-NF-κB peptides (Tat-NBD) alleviates infection-sensitized hypoxic-ischemic brain injury.

Perinatal infection aggravates neonatal hypoxic-ischemic (HI) brain injury and may interfere with therapeutic hypothermia. While the NF-κB signaling pathway has been implicated in microglia activation in infection-sensitized HI, the current therapeutic strategies rely on systemic intervention, which could impair neonatal immunity and increase the risk of severe infection. To devise a brain-targeted anti-NF-κB strategy, we examined the effects of intranasal delivery of tat-NBD peptides in two animal models of neonatal infection-sensitized HI.

Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition.

Neurofibromatosis type 1 (NF1) is a common genetic disease that predisposes 30-50 % of affected individuals to develop plexiform neurofibromas. We found that macrophage infiltration of both mouse and human neurofibromas correlates with disease progression. Macrophages accounted for almost half of neurofibroma cells, leading us to hypothesize that nerve macrophages are inflammatory effectors in neurofibroma development and/or growth.

Plasminogen activator inhibitor-1 mitigates brain injury in a rat model of infection-sensitized neonatal hypoxia-ischemia.

Intrauterine infection exacerbates neonatal hypoxic-ischemic (HI) brain injury and impairs the development of cerebral cortex. Here we used low-dose lipopolysaccharide (LPS) pre-exposure followed by unilateral cerebral HI insult in 7-day-old rats to study the pathogenic mechanisms. We found that LPS pre-exposure blocked the HI-induced proteolytic activity of tissue-type plasminogen activator (tPA), but significantly enhanced NF-κB signaling, microglia activation, and the production of pro-inflammatory cytokines in newborn brains.

CMV infection attenuates the disease course in a murine model of multiple sclerosis.

Recent evidence in multiple sclerosis (MS) suggests that active CMV infection may result in more benign clinical disease. The goal of this pilot study was to determine whether underlying murine CMV (MCMV) infection affects the course of the Theiler's murine encephalitis virus (TMEV) induced murine model of MS. A group of eight TMEV-infected mice were co-infected with MCMV at 2 weeks prior to TMEV infection while a second group of TMEV-infected mice received MCMV two weeks post TMEV.

Contrasting roles for CD4 vs. CD8 T-cells in a murine model of virally induced "T1 black hole" formation.

MRI is sensitive to tissue pathology in multiple sclerosis (MS); however, most lesional MRI findings have limited correlation with disability. Chronic T1 hypointense lesions or "T1 black holes" (T1BH), observed in a subset of MS patients and thought to represent axonal damage, show moderate to strong correlation with disability. The pathogenesis of T1BH remains unclear.

A tool for measuring workers' sitting time by domain: the Workforce Sitting Questionnaire.

Background: Sitting time is an emerging health risk, and many working adults spend large amounts of time sitting each day. It is important to have reliable and accurate measurement tools to assess sitting time in different contexts.

Objective: To validate the Workforce Sitting Questionnaire (WSQ), an adapted measure of total and domain-specific sitting time based on work and non-workdays for use in working adults.

Validity of the occupational sitting and physical activity questionnaire.

Purpose: Sitting at work is an emerging occupational health risk. Few instruments designed for use in population-based research measure occupational sitting and standing as distinct behaviors. This study aimed to develop and validate brief measure of occupational sitting and physical activity.

The 2010 Haiti earthquake: a pathology perspective aboard the USNS Comfort.

The US Navy hospital ship USNS Comfort played an integral role in the initial phases of Operation Unified Response-Haiti following the devastating earthquake that struck near Port-Au-Prince, Haiti, on January 12, 2010. Deployed to Haiti from its home in Baltimore, Maryland, just 4 days after the earthquake, the USNS Comfort would become the region's primary tertiary casualty receiving center for 6 weeks. The pathology and laboratory department staff onboard the ship helped support the mission and experienced unique mass casualty/disaster relief scenarios while underway.

Long term antipsychotic treatment does not alter metabolite concentrations in rat striatum: an in vivo magnetic resonance spectroscopy study.

Proton magnetic resonance spectroscopy (MRS) studies of schizophrenic patients generally reveal reduced levels of N-acetyl aspartate (NAA) when compared with healthy controls. Whether this reduction is due to the disease or to the drugs used for treatment remains an open question. Numerous human and animal studies have attempted to determine the effects of antipsychotics on NAA levels with mixed results.

Preclincial testing of sorafenib and RAD001 in the Nf(flox/flox) ;DhhCre mouse model of plexiform neurofibroma using magnetic resonance imaging.

Background: Neurofibromatosis type 1 (NF1) is an inherited disease predisposing affected patients to variable numbers of benign neurofibromas. To date there are no effective chemotherapeutic drugs available for this slow growing tumor. Molecularly targeted agents that aim to slow neurofibroma growth are being tested in clinical trials.

Ex vivo diffusion tensor imaging and neuropathological correlation in a murine model of hypoxia-ischemia-induced thrombotic stroke.

Diffusion tensor imaging (DTI) is a powerful method to visualize white matter, but its use in patients with acute stroke remains limited because of the lack of corresponding histologic information. In this study, we addressed this issue using a hypoxia-ischemia (HI)-induced thrombotic model of stroke in adult mice. At 6, 15, and 24  hours after injury, animals were divided into three groups for (1) in vivo T2- and diffusion-weighted magnetic resonance imaging, followed by histochemistry, (2) ex vivo DTI and electron microscopy, and (3) additional biochemical or immunochemical assays.

Magnetic resonance imaging assessment of cardiac dysfunction in δ-sarcoglycan null mice.

Delta-sarcoglycan (δ-sarcoglycan) null, Scgd(-/-), mice develop cardiac and skeletal muscle histopathological alterations similar to those in humans with limb-girdle muscular dystrophy. The objective of this study was to assess the feasibility of using MRI to investigate cardiac dysfunction in Scgd(-/-) mice. Cardiac MRI of 8 month old Scgd(-/-) and wild type (WT) mice was performed.

Brain atrophy correlates with functional outcome in a murine model of multiple sclerosis.

White matter (WM) lesions are the classic pathological hallmarks of multiple sclerosis (MS). However, MRI-based WM lesion load shows relatively poor correlation with functional outcome, resulting in the "clinico-radiological paradox" of MS. Unlike lesion based measures, volumetric MRI assessment of brain atrophy shows a strong correlation with functional outcome, and the presence of early atrophy predicts a worse disease course.

Therapeutic administration of plasminogen activator inhibitor-1 prevents hypoxic-ischemic brain injury in newborns.

Disruption of the integrity of the blood-brain barrier (BBB) is an important mechanism of cerebrovascular diseases, including neonatal cerebral hypoxia-ischemia (HI). Although both tissue-type plasminogen activator (tPA) and matrix metalloproteinase-9 (MMP-9) can produce BBB damage, their relationship in neonatal cerebral HI is unclear. Here we use a rodent model to test whether the plasminogen activator (PA) system is critical for MMP-9 activation and HI-induced brain injury in newborns.

Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy.

Hypoxia is a critical factor for cell death or survival in ischemic stroke, but the pathological consequences of combined ischemia-hypoxia are not fully understood. Here we examine this issue using a modified Levine/Vannucci procedure in adult mice that consists of unilateral common carotid artery occlusion and hypoxia with tightly regulated body temperature. At the cellular level, ischemia-hypoxia produced proinflammatory cytokines and simultaneously activated both prosurvival (eg, synthesis of heat shock 70 protein, phosphorylation of ERK and AKT) and proapoptosis signaling pathways (eg, release of cytochrome c and AIF from mitochondria, cleavage of caspase-9 and -8).

Making memories: a cross-sectional investigation of episodic memory encoding in childhood using FMRI.

In adults, the neural substrate associated with encoding memories connected to a specific time and place include the prefrontal cortex and medial temporal lobe (MTL). Using functional magnetic resonance imaging, this research studied the developmental trajectory of this frontal-MTL system by comparing 7- and 8-year-old children to those who were 10 or older in conditions that promoted episodic encoding. In 1 condition, participants generated verbs from nouns heard; in another, they listened to short stories for comprehension.

High-resolution functional MRI at 3T in healthy and epilepsy subjects: hippocampal activation with picture encoding task.

Functional MRI (fMRI) studies of memory with coarse resolution of 4 x 4 x 5 mm often fail to demonstrate blood oxygenation level-dependent (BOLD) activation in the hippocampal formation. This failure occurs when nonactivating white matter is averaged with the signal from hippocampal gray matter, attenuating the total BOLD signal from a single voxel due to the "partial volume effect." In this study, we evaluated the suitability of high-resolution fMRI at 3T (voxel size 2 x 2 x 3 mm) for improved visualization of hippocampal activation during memory encoding in 21 healthy and 6 epilepsy subjects.