An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents.

Chronic, unresolved stress is a major risk factor for the development of clinical depression. While many preclinical models of stress-induced depression have been reported, the unpredictable chronic mild stress (UCMS) protocol is an established translationally-relevant model for inducing behavioral symptoms commonly associated with clinical depression, such as anhedonia, altered grooming behavior, and learned helplessness in rodents. The UCMS protocol also induces physiological (e.

Protective effect of sex on chronic stress- and depressive behavior-induced vascular dysfunction in BALB/cJ mice.

The presence of chronic, unresolvable stresses leads to negative health outcomes, including development of clinical depression/depressive disorders, with outcome severity being correlated with depressive symptom severity. One of the major outcomes associated with chronic stress and depression is the development of cardiovascular disease (CVD) and an elevated CVD risk profile. However, in epidemiological research, sex disparities are evident, with premenopausal women suffering from depressive symptoms more acutely than men, but also demonstrating a relative protection from the onset of CVD.

Impact of increased intramuscular perfusion heterogeneity on skeletal muscle microvascular hematocrit in the metabolic syndrome.

Objective: To determine HMV and PS in skeletal muscle of OZR and evaluate the impact of increased microvascular perfusion heterogeneity on mass transport/exchange.

Methods: The in situ gastrocnemius muscle from OZR and LZR was examined under control conditions and following pretreatment with TEMPOL (antioxidant)/SQ-29548 (PGH2 /TxA2 receptor antagonist), phentolamine (adrenergic antagonist), or all agents combined. A spike input of a labeled blood tracer cocktail was injected into the perfusing artery.

Dual acute proinflammatory and antifibrotic pulmonary effects of short palate, lung, and nasal epithelium clone-1 after exposure to carbon nanotubes.

Carbon nanotubes (CNTs; allotropes of carbon with a cylindrical nanostructure) have emerged as one of the most commonly used types of nanomaterials, with numerous applications in industry and biomedicine. However, the inhalation of CNTs has been shown to elicit pulmonary toxicity, accompanied by a robust inflammatory response with an early-onset fibrotic phase. Epithelial host-defense proteins represent an important component of the pulmonary innate immune response to foreign inhalants such as particles and bacteria.

Differential impact of dilator stimuli on increased myogenic activation of cerebral and skeletal muscle resistance arterioles in obese zucker rats.

Objective: To use the OZR model of the metabolic syndrome to determine the impact of dilator stimuli on MA of GA and MCA. We tested the hypothesis that increased oxidant stress and TxA2 exacerbate MA, and prevent its blunting with dilator stimuli, in OZR.

Methods: GA/MCA from OZR and LZR was pressurized ex vivo.

Blunted temporal activity of microvascular perfusion heterogeneity in metabolic syndrome: a new attractor for peripheral vascular disease?

A key clinical outcome for peripheral vascular disease (PVD) in patients is a progressive decay in skeletal muscle performance and its ability to resist fatigue with elevated metabolic demand. We have demonstrated that PVD in obese Zucker rats (OZR) is partially due to increased perfusion distribution heterogeneity at successive microvascular bifurcations within skeletal muscle. As this increased heterogeneity (γ) is longitudinally present in the network, its cumulative impact is a more heterogeneous distribution of perfusion between terminal arterioles than normal, causing greater regional tissue ischemia.

Carbon nanotubes enhance metastatic growth of lung carcinoma via up-regulation of myeloid-derived suppressor cells.

Metastatic establishment and growth of Lewis lung carcinoma is promoted by single-walled carbon nanotubes (SWCNT) in C57BL6/J mice. The effect is mediated by increased local and systemic accumulation of myeloid-derived suppressor cells (MDSC), as their depletion abrogated pro-tumor activity in vivo. These data are important for the design of novel theranostics platforms with modules capable of depleting or functionally suppressing MDSC to ensure effective immunosurveillance in the tumor microenvironment.

Graphene oxide, but not fullerenes, targets immunoproteasomes and suppresses antigen presentation by dendritic cells.

Graphene oxide (GO) and C60 - or C60 -TRIS fullerenes, internalized by murine dendritic cells (DCs), differently affect their abilities to present antigens to T-cells. While C60 -fullerenes stimulate the ovalbumin-specific MHC class I-restricted T-cell response, GO impairs the stimulatory potential of DCs. In contrast to C60 -fullerenes, GO decreases the intracellular levels of LMP7 immunoproteasome subunits required for processing of protein antigens.