Embracing Heterogeneity in The Multicenter Stroke Preclinical Assessment Network (SPAN) Trial.

The Stroke Preclinical Assessment Network (SPAN) is a multicenter preclinical trial platform using rodent models of transient focal cerebral ischemia to address translational failure in experimental stroke. In addition to centralized randomization and blinding and large samples, SPAN aimed to introduce heterogeneity to simulate the heterogeneity embodied in clinical trials for robust conclusions. Here, we report the heterogeneity introduced by allowing the 6 SPAN laboratories to vary most of the biological and experimental model variables and the impact of this heterogeneity on middle cerebral artery occlusion (MCAo) performance.

The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results.

Cerebral ischemia and reperfusion initiate cellular events in brain that lead to neurological disability. Investigating these cellular events provides ample targets for developing new treatments. Despite considerable work, no such therapy has translated into successful stroke treatment.

Adrenal cortex stimulation with hCG in spayed female dogs with Cushing's syndrome: Is the LH-dependent variant possible?

Background: The expression and overexpression of luteinizing hormone (LH) receptors in the canine adrenal gland cortex have been reported. Therefore, it was hypothesized that a LH-dependent form of Cushing's syndrome (CS) could exist in dogs.

Aim: To assess whether the adrenal gland post-ovariectomy (OVx) exhibits a greater response to adrenocorticotrophin (ACTH) stimulation; to evaluate whether the adrenal gland responds to human chorionic gonadotropin (hCG) stimulation by increasing the release of cortisol; and to consider whether hCG stimulus testing would be useful as a diagnosis for possible cases of LH-dependent CS.

Childhood acute poisoning in the Italian North-West area: a six-year retrospective study.

Background: Data about acute poisoning in Italian pediatric patients are obsolete or absent. This study would partially fill this exiting gap and compare the scene with others around the world.

Methods: A retrospective evaluation was performed on a 2012-2017 data registry of the Children's Emergency Department at the Regina Margherita Hospital of Turin, where 1030 children under age 14 were accepted with a diagnosis of acute intoxication.

Uncovering the Rosetta Stone: Report from the First Annual Conference on Key Elements in Translating Stroke Therapeutics from Pre-Clinical to Clinical.

The first annual Stroke Translational Research Advancement Workshop (STRAW), entitled "Uncovering the Rosetta Stone: Key Elements in Translating Stroke Therapeutics from Pre-Clinical to Clinical" was held at the University of Kentucky on October 4-5, 2017. This workshop was organized by the Center for Advanced Translational Stroke Science. The workshop consisted of 2 days of activities.

Decrease in the AP-2 DNA-Binding Activity and in the Protein Expression of AP-2 a and AP-2 b in Frontal Cortex of Rats Treated with Lithium for 6 Weeks.

This corrects the article DOI: 10.1038/ajg.2016.

The flavonoid Baicalein attenuates cuprizone-induced demyelination via suppression of neuroinflammation.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, and axonal pathology. Baicalein isolated from the roots of Scutellaria baicalensis has been shown to exert anti-inflammatory and antioxidant effects. The cuprizone model is an established mouse model of MS and causes demyelination and motor dysfunction and induces neuroinflammation, such as glial activation and pro-inflammatory cytokine production.

The Science of Vascular Contributions to Cognitive Impairment and Dementia (VCID): A Framework for Advancing Research Priorities in the Cerebrovascular Biology of Cognitive Decline.

The World Health Organization reports that 47.5 million people are affected by dementia worldwide. With aging populations and 7.

Vascular contributions to cognitive impairment and dementia including Alzheimer's disease.

Scientific evidence continues to demonstrate the linkage of vascular contributions to cognitive impairment and dementia such as Alzheimer's disease. In December, 2013, the Alzheimer's Association, with scientific input from the National Institute of Neurological Disorders and Stroke and the National Heart, Lung and Blood Institute from the National Institutes of Health, convened scientific experts to discuss the research gaps in our understanding of how vascular factors contribute to Alzheimer's disease and related dementia. This manuscript summarizes the meeting and the resultant discussion, including an outline of next steps needed to move this area of research forward.

Toll-like receptors, immunoproteasome and regulatory T cells in children with Henoch-Schönlein purpura and primary IgA nephropathy.

Background: Henoch-Schönlein purpura (HSP) nephritis and primary IgA nephropathy (pIgAN) present with glomerular IgA deposits, but differ with regard to clinical features. The suspected involvement of different immune system pathways is largely unknown.

Methods: This study was aimed at investigating some of the immunological features including Toll-like receptors (TLR), proteasome (PS)/immunoproteasome (iPS) switch, and the regulatory T cell system (Treg/Th17 cells) in 63 children with HSP with/without renal involvement and in 25 with pIgAN.

Alterations of brain eicosanoid synthetic pathway in multiple sclerosis and in animal models of demyelination: role of cyclooxygenase-2.

Inflammation is a physiological response to exogenous and endogenous stimuli and, together with demyelination and immune system activation, is one of the key features of multiple sclerosis (MS). Arachidonic acid (AA) metabolism by cyclooxygenase (COX) and lipoxygenase (LO) enzymes leads to the production of proinflammatory eicosanoids, and stimulates cytokine production and activation of microglia and astrocytes, thereby contributing to MS pathology. Current therapies target the immune system but do not specifically target AA-related inflammatory pathway.

Unesterified docosahexaenoic acid is protective in neuroinflammation.

Docosahexaenoic acid (22:6n-3) is the major brain n-3 polyunsaturated fatty acid and it is possible that docosahexaenoic acid is anti-inflammatory in the brain as it is known to be in other tissues. Using a combination of models including the fat-1 transgenic mouse, chronic dietary n-3 polyunsaturated fatty acid modulation in transgenic and wild-type mice, and acute direct brain infusion, we demonstrated that unesterified docosahexaenoic acid attenuates neuroinflammation initiated by intracerebroventricular lipopolysaccharide. Hippocampal neuroinflammation was assessed by gene expression and immunohistochemistry.

Genetic variation of germination cold tolerance in Japanese rice germplasm.

Low temperatures at the initial stages of rice development prevent fast germination and seedling establishment and may cause significant productivity losses. In order to develop rice cultivars exhibiting cold tolerance, it is necessary to investigate genetic resources, providing basic knowledge to allow the introduction of genes involved in low temperature germination ability from accessions into elite cultivars. Japanese rice accessions were evaluated at the germination under two conditions: 13°C for 28 days (cold stress) and 28°C for seven days (optimal temperature).

Cyclooxygenase-1 inhibition reduces amyloid pathology and improves memory deficits in a mouse model of Alzheimer's disease.

Several epidemiological and preclinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase (COX), reduce the risk of Alzheimer's disease (AD) and can lower β-amyloid (Aβ) production and inhibit neuroinflammation. However, follow-up clinical trials, mostly using selective cyclooxygenase (COX)-2 inhibitors, failed to show any beneficial effect in AD patients with mild to severe cognitive deficits. Recent data indicated that COX-1, classically viewed as the homeostatic isoform, is localized in microglia and is actively involved in brain injury induced by pro-inflammatory stimuli including Aβ, lipopolysaccharide, and interleukins.

3,6'-Dithiothalidomide, a new TNF-α synthesis inhibitor, attenuates the effect of Aβ1-42 intracerebroventricular injection on hippocampal neurogenesis and memory deficit.

Evidence indicates altered neurogenesis in neurodegenerative diseases associated with inflammation, including Alzheimer's disease (AD). Neuroinflammation and its propagation have a critical role in the degeneration of hippocampal neurons, cognitive impairment, and altered neurogenesis. Particularly, tumor necrosis factor (TNF)-α plays a central role in initiating and regulating the cytokine cascade during an inflammatory response and is up-regulated in brain of AD patients.