Injectable, reversibly thermoresponsive captopril-laden hydrogel for the local treatment of sensory loss in diabetic neuropathy.

A major and irreversible complication of diabetes is diabetic peripheral neuropathy (DPN), which can lead to significant disability and decreased quality of life. Prior work demonstrates the peptide hormone Angiotensin II (Ang II) is released locally in neuropathy and drives inflammation and impaired endoneurial blood flow. Therefore, we proposed that by utilizing a local thermoresponsive hydrogel injection, we could deliver inhibitors of angiotensin-converting enzyme (ACE) to suppress Ang II production and reduce nerve dysfunction in DPN through local drug release.

Neuromuscular Polytrauma Pain is Resolved by Macrophage COX-2 Nanoimmunomodulation.

Soft tissue injuries often involve muscle and peripheral nerves and are qualitatively distinct from single-tissue injuries. Prior research suggests that damaged innervation compromises wound healing. To test this in a traumatic injury context, we developed a novel mouse model of nerve and lower limb polytrauma, which features greater pain hypersensitivity and more sustained macrophage infiltration than either injury in isolation.

Single-cell analysis of age-related changes in leukocytes of diabetic mouse hindpaws.

Complications associated with Type 1 and Type 2 diabetes, such as diabetic peripheral neuropathy and diabetic foot ulcers, are a growing health-care concern. In addition, this concern increases as diabetic patients age due to their increased susceptibility to complications. To address this growing problem, it is important to understand fluctuations in physiology which lead to pathological changes associated with the metabolic disturbances of diabetes.

Sustained pain and macrophage infiltration in a mouse muscle contusion model.

Introduction/aims: Prior studies have emphasized the role of inflammation in the response to injury and muscle regeneration, but little emphasis has been placed on characterizing the relationship between innate inflammation, pain, and functional impairment. The aim of our study was to determine the contribution of innate immunity to prolonged pain following muscle contusion.

Methods: We developed a closed-impact mouse model of muscle contusion and a macrophage-targeted near-infrared fluorescent nanoemulsion.

Age-Dependent Effects of Transgenic 2D2 Mice Used to Induce Passive Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice.

Introduction: Multiple sclerosis (MS) is a neurodegenerative autoimmune disease that worsens with age. Here, we examined the influence of age on passive experimental autoimmune encephalomyelitis (P-EAE), a model to study MS, using young and mature adult 2D2 transgenic donor mice to induce pathology in WT C57BL6/J mice.

Methods: Lymphocytes from young adult (i.

Sensory neuron dysfunction in orthotopic mouse models of colon cancer.

Reports of neurological sequelae related to colon cancer are largely restricted to rare instances of paraneoplastic syndromes, due to autoimmune reactions. Systemic inflammation associated with tumor development influences sensory neuron function in other disease models, though the extent to which this occurs in colorectal cancer is unknown. We induced orthotopic colorectal cancer via orthotopic injection of two colorectal cancer cell lines (MC38 and CT26) in two different mouse strains (C57BL/6 and Balb/c, respectively).

Tracking macrophages in diabetic neuropathy with two-color nanoemulsions for near-infrared fluorescent imaging and microscopy.

Background: The incidence of diabetes and diabetic peripheral neuropathy continues to rise, and studies have shown that macrophages play an important role in their pathogenesis. To date, macrophage tracking has largely been achieved using genetically-encoded fluorescent proteins. Here we present a novel two-color fluorescently labeled perfluorocarbon nanoemulsion (PFC-NE) designed to monitor phagocytic macrophages in diabetic neuropathy in vitro and in vivo using non-invasive near-infrared fluorescent (NIRF) imaging and fluorescence microscopy.

The CB Receptor Differentially Regulates IFN-γ Production and in Experimental Autoimmune Encephalomyelitis.

Activation of the peripheral immune system and the infiltration of immune cells into the central nervous system are both key features of the experimental autoimmune encephalomyelitis (EAE) model. By exploring how the endocannabinoid system works to modulate this response, we can better understand how exogenous cannabinoids, such as THC, might be used to modulate the immune responses of multiple sclerosis patients. In this study, we examined the role of the CB receptor in IFN-γ and IL-17A production in the EAE model and stimulations of naive splenocytes using mice and wild-type (WT) littermates.

CBD Suppression of EAE Is Correlated with Early Inhibition of Splenic IFN-γ + CD8+ T Cells and Modest Inhibition of Neuroinflammation.

In this study cannabidiol (CBD) was administered orally to determine its effects and mechanisms in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). We hypothesized that 75 mg/kg of oral CBD given for 5 days after initiation of disease would reduce EAE severity through suppression of either the early peripheral immune or late neuroimmune response. EAE was induced in C57BL/6 mice at two different magnitudes, and peripheral inflammatory and neuroinflammatory responses were measured at days 3, 10, and 18.

Immune Responses Regulated by Cannabidiol.

Cannabidiol (CBD) as Epidiolex (GW Pharmaceuticals) was recently approved by the U.S. Food and Drug Administration (FDA) to treat rare forms of epilepsy in patients 2 years of age and older.

Neuroinflammation and B-Cell Phenotypes in Cervical and Lumbosacral Regions of the Spinal Cord in Experimental Autoimmune Encephalomyelitis in the Absence of Pertussis Toxin.

Objectives: The active experimental autoimmune encephalomyelitis (EAE) model is often initiated using myelin oligodendrocyte glycoprotein (MOG) immunization followed by pertussis toxin (PTX) to study multiple sclerosis. However, PTX inactivates G protein-coupled receptors, and with increasing knowledge of the role that various G protein-coupled receptors play in immune homeostasis, it is valuable to establish neuroimmune endpoints for active EAE without PTX.

Methods: Female C57BL/6 mice were immunized with MOG35-55 peptide in Complete Freund's Adjuvant and neuroinflammation, including central nervous system B-cell infiltration, was compared to saline-injected mice.