Hypoxia-inducible factor-1␣ (HIF-1␣) plays an essential role in cellular and systemic O 2 homeostasis by regulating the expression of genes important in glycolysis, erythropoiesis, angiogenesis, and catecholamine metabolism. It is also believed to be a key component of the cellular response to hypoxia and ischemia under pathophysiological conditions, such as stroke. To clarify the function of HIF-1␣ in the brain, we exposed adult mice with late-stage brain deletion of HIF-1␣ to hypoxic injuries. Contrary to expectations, the brains from the HIF-1␣-deficient mice were protected from hypoxia-induced cell death. These surprising findings suggest that decreasing the level of HIF-1␣ can be neuroprotective. Gene chip expression analysis revealed that, contrary to expectations, the majority of hypoxia-dependent gene-expression changes were unaltered, whereas a specific downregulation of apoptotic genes was observed in the HIF-1␣-deficient mice. Although the role of HIF-1␣ has been extensively characterized in vitro, in cancer models, and in chronic preconditioning paradigms, this is the first study to evaluate the role of HIF-1␣ in vivo in the brain in response to acute hypoxia/ischemia. Our data suggest, that in acute hypoxia, the neuroprotection found in the HIF-1␣-deficient mice is mechanistically consistent with a predominant role of HIF-1␣ as proapoptotic and loss of function leads to neuroprotection. Furthermore, our data suggest that functional redundancy develops after excluding HIF-1␣, leading to the preservation of gene expression regulating the majority of other previously characterized HIF-dependent genes.

Administration of NO in experimental stroke reduces stroke lesion volume in permanent and transient models. This may be mediated, in part, by increased cerebral perfusion in permanent models. These data support clinical trials in stroke patients, although the presence of a narrow therapeutic time window may be a limiting factor.

No abstract

No abstract

Nitric oxide (NO) is produced in the CNS following injury-induced expression of inducible nitric oxide synthase (iNOS), yet its role as protective or damaging is unclear. Previous studies investigating the therapeutic potential of female sex steroids in stroke and trauma suggest that NO from this source is harmful, since oestradiol and progesterone decreased the level of iNOS expression in vitro and improved neurological outcome. We investigated the effects of progesterone on stroke-induced expression of iNOS in mice, as well as cytokine-induced expression of iNOS and its transcriptional activators in cells relevant to injury. We observed a significant reduction in stroke-induced iNOS transcript in progesterone-treated mice and in cultured macrophages. In contrast, progesterone significantly amplifed cytokine-induced iNOS mRNA in cultured primary astrocytes, although the expression of protein was decreased. We sequenced upstream of the 1.5 kb reported iNOS promoter region and identified a potential progesterone response element (PRE). Astrocytes transiently transfected with iNOS promoter/CAT reporter gene constructs containing the PRE displayed a significant increase in induction of CAT expression after progesterone treatment, and this was diminished in cells transfected with a construct containing a disrupted PRE. These observations suggest the involvement of iNOS in the neuroprotective effects of progesterone.

There is limited information on the risk of eating disorders and body image of elite male athletes. However, research suggests there are some athletes who have poor body image and they may be at increased risk of developing eating disorders. Therefore, the current study investigated risk of eating disorders, body image, and the relationship with age, in elite rugby union players during their pre-season training period.This cross-sectional study was undertaken at the start of the pre-season amongst elite rugby union players in New Zealand. Twenty-six professional rugby union players completed a 49-item questionnaire on body image and disordered eating. A 'body image score' was calculated from questionnaire subscales including 'drive for thinness', 'bulimia' and 'body dissatisfaction', with total scores above twenty indicative of poor body image.Body image scores varied from 8-39 out of a possible 0-100. Disordered eating behaviours were reported, including binge eating at least once a week (15%, n=4/26), pathogenic weight control use (4%, n=1/26) and avoidance of certain foods (77%, n=20/26). There was a statistically significant inverse association between the bulimia subscale and age (P = 0.034).At the start of the pre-season training period, many elite rugby union players experience disturbances in body image. The prevalence of disordered eating behaviours is of concern, and needs to be minimised due to the negative impact on health and performance. A focus on assessment and education of younger male rugby players may be required in order to reduce disordered eating patterns.

We investigated whether the neuroprotective mechanism of progesterone involves modulation of the neurotrophin brain-derived neurotrophic factor (BDNF). We show that BDNF expression is upregulated following cerebral ischemia in mice and in C6 glioma cells exposed to cytokines, while reduced in cerebellar granule neurons exposed to the excitotoxin glutamate. Progesterone was without additional effect on BDNF in these paradigms. Progesterone also protected PC12 neurons deprived of trophic support, while it decreased cerebellar granule neuron viability. Both the effects of progesterone and the expression of BDNF can clearly vary following stroke-like injuries, however we found no evidence for a neuroprotective relationship between progesterone and BDNF.

Dementia continues to be the most burdening neurocognitive disorder, having a negative impact on the lives of millions. The search for biomarkers to improve the clinical diagnosis of dementia is ongoing, with the focus on effective use of readily accessible peripheral markers. In this review, we concentrate on platelets as biomarkers of dementia and analyze their potential as easily-accessible clinical biomarkers for various subtypes of dementia. Current platelet protein biomarkers that have been investigated for their clinical utility in the diagnosis of dementia, in particular Alzheimer's disease, include amyloid-β protein precursor (AβPP), the AβPP secretases (BACE1 and ADAM10), α-synuclein, tau protein, serotonin, cholesterol, phospholipases, clusterin, IgG, surface receptors, MAO-B, and coated platelets. Few of them, i.e., platelet tau, AβPP (particularly with regards to coated platelets) and secreted ADAM10 and BACE1 show the most promise to be taken forward into clinical setting to diagnose dementia. Aside from protein biomarkers, changes in factors such as mean platelet volume have the potential to play a very specific role in both the dementia diagnosis and prognosis. This review raises a number of research questions for consideration before application of the above biomarkers to routine clinical setting. It is without doubt that there is a need for more clarification on the effects of dementia on platelet morphology and protein content before these changes can be clinically applied as dementia biomarkers and explored further in differentiating distinct dementia subtypes.