Effectiveness of LISTEN on loneliness, neuroimmunological stress response, psychosocial functioning, quality of life, and physical health measures of chronic illness.

Objectives: Loneliness is a biopsychosocial determinant of health and contributes to physical and psychological chronic illnesses, functional decline, and mortality in older adults. This paper presents the results of the first randomized trial of LISTEN, which is a new cognitive behavioral intervention for loneliness, on loneliness, neuroimmunological stress response, psychosocial functioning, quality of life, and measures of physical health.

Methods: The effectiveness of LISTEN was evaluated in a sample population comprising 27 lonely, chronically ill, older adults living in Appalachia.

Single low-dose lipopolysaccharide preconditioning: neuroprotective against axonal injury and modulates glial cells.

Aim: Over 7 million traumatic brain injuries (TBI) are reported each year in the United States. However, treatments and neuroprotection following TBI are limited because secondary injury cascades are poorly understood. Lipopolysaccharide (LPS) administration before controlled cortical impact can contribute to neuroprotection.

Using Gene Expression Analysis to Examine Changes in Loneliness, Depression and Systemic Inflammation in Lonely Chronically Ill Older Adults.

Purpose: The purpose of this study was to evaluate the effectiveness of LISTEN (Loneliness Intervention) on loneliness, depression, physical health, systemic inflammation, and genomic expression in a sample of lonely, chronically ill, older adults.

Methods: This was a prospective, longitudinal randomized trial of LISTEN, a novel intervention based on theories of narrative and cognitive restructuring to target specific aspects of loneliness. Twenty-three older, lonely, chronically ill adults were recruited from a family medicine clinic in West Virginia.

A genomic profile of the immune response to stroke with implications for stroke recovery.

Objectives: The objectives of this study were to determine the change in gene expression between two time points following stroke and to identify biomarkers of stroke recovery through gene expression profiling and pathway analysis.

Methods: Peripheral blood was collected from 34 ischemic stroke patients (confirmed by magnetic resonance imaging) ≥18 years of age, within 24 hr of symptom onset and 24-48 hr later, and from healthy controls. The Modified Rankin Scale (MRS) was used to determine 30-day recovery.

Early activation of STAT3 regulates reactive astrogliosis induced by diverse forms of neurotoxicity.

Astrogliosis, a cellular response characterized by astrocytic hypertrophy and accumulation of GFAP, is a hallmark of all types of central nervous system (CNS) injuries. Potential signaling mechanisms driving the conversion of astrocytes into "reactive" phenotypes differ with respect to the injury models employed and can be complicated by factors such as disruption of the blood-brain barrier (BBB). As denervation tools, neurotoxicants have the advantage of selective targeting of brain regions and cell types, often with sparing of the BBB.

Sesamol: a Treatment for Diabetes-Associated Blood-Brain Barrier Dysfunction.

Diabetes is a long-standing disease that leads to secondary complications of capillaries such as retinopathy, nephropathy and neuropathy. Emerging evidence suggests that diabetes may also affect the cerebromicrovasculature, the blood-brain barrier (BBB), and lead to changes in the brain that affect cognition and mood. Therefore, it is important to identify natural compounds that may have therapeutic benefit for reducing BBB dysfunction and improve patient quality of life.

Elucidating the severity of preclinical traumatic brain injury models: a role for functional assessment?

Background: Concussion remains a symptom-based diagnosis clinically, yet preclinical studies investigating traumatic brain injury, of which concussion is believed to represent a "mild" form, emphasize histological end points with functional assessments often minimized or ignored all together. Recently, clinical studies have identified the importance of cognitive and neuropsychiatric symptoms, in addition to somatic concerns, following concussion. How these findings may translate to preclinical studies is unclear at present.

C-reactive protein and long-term ischemic stroke prognosis.

C-reactive protein (CRP) is an inflammatory biomarker of inflammation and may reflect progression of vascular disease. Conflicting evidence suggests CRP may be a prognostic biomarker of ischemic stroke outcome. Most studies that have examined the relationship between CRP and ischemic stroke outcome have used mortality or subsequent vascular event as the primary outcome measure.

Admission neutrophil-lymphocyte ratio predicts 90 day outcome after endovascular stroke therapy.

Objective: Immune dysregulation influences outcome following acute ischemic stroke (AIS). Admission white blood cell (WBC) counts are routinely obtained, making the neutrophil-lymphocyte ratio (NLR) a readily available biomarker of the immune response to stroke. This study sought to identify the relationship between NLR and 90 day AIS outcome.

The transcriptome of cerebral ischemia.

The molecular causality and response to stroke is complex. Yet, much of the literature examining the molecular response to stroke has focused on targeted pathways that have been well-characterized. Consequently, our understanding of stroke pathophysiology has made little progress by way of clinical therapeutics since tissue plasminogen activator was approved for treatment nearly a decade ago.

Targeting the neurovascular unit for treatment of neurological disorders.

Drug discovery for CNS disorders has been restricted by the inability for therapeutic agents to cross the blood-brain barrier (BBB). Moreover, current drugs aim to correct neuron cell signaling, thereby neglecting pathophysiological changes affecting other cell types of the neurovascular unit (NVU). Components of the NVU (pericytes, microglia, astrocytes, and neurons, and basal lamina) act as an intricate network to maintain the neuronal homeostatic microenvironment.

NOX2 inhibition with apocynin worsens stroke outcome in aged rats.

This study utilized middle cerebral artery occlusion (MCAO) with tissue plasminogen activator (tPA) to assess inhibition of the NOX2 isoform of NADPH oxidase on brain injury and functional recovery in aged rats. Effects of NOX2 on the degree of brain injury and functional recovery following MCAO and tPA reperfusion was assessed in young adult and aged rats. Rats received apocynin (NOX2 inhibitor; 5 mg/kg) or saline 30 min prior to MCAO.

Streptozotocin-induced diabetes progressively increases blood-brain barrier permeability in specific brain regions in rats.

This study investigated the effects of streptozotocin-induced diabetes on the functional integrity of the blood-brain barrier in the rat at 7, 28, 56, and 90 days, using vascular space markers ranging in size from 342 to 65,000 Da. We also examined the effect of insulin treatment of diabetes on the formation and progression of cerebral microvascular damage and determined whether observed functional changes occurred globally throughout the brain or within specific brain regions. Results demonstrate that streptozotocin-induced diabetes produced a progressive increase in blood-brain barrier permeability to small molecules from 28 to 90 days and these changes in blood-brain barrier permeability were region specific, with the midbrain most susceptible to diabetes-induced microvascular damage.

Expression of a familial amyotrophic lateral sclerosis-associated mutant human superoxide dismutase in yeast leads to decreased mitochondrial electron transport.

Strains of Saccharomyces cerevisiae that express either the wild type or the amyotrophic lateral sclerosis-associated mutant human copper-zinc superoxide dismutase (SOD1) proteins A4V and G93A, respectively, in a yeast SOD1-deficient parent strain were used to investigate the hypothesis that expression of a mutant SOD1 protein causes deficient mitochondrial electron transport as a possible mechanism for disease induction. Mitochondria isolated from the wild type SOD1-expressing yeast were identical to mitochondria from the parent strain in heme content and activities of complexes II, III, and IV. Mitochondria isolated from the A4V-expressing yeast had decreased rates of electron transport in complexes II+III, III, and IV and corresponding decreases in hemes b, c-c1, and a-a3 content compared to mitochondria from wild type human SOD1-expressing yeast.

Prostate cancer cell proliferation is influenced by leptin.

Background: Obesity is considered a risk for many cancers. Serum leptin levels are often elevated in obese people. Leptin acts as a mitogenic agent in many tissues; therefore, it may act to promote cancer cell growth.