Vulnerability to stroke: implications of perinatal programming of the hypothalamic-pituitary-adrenal axis.

Chronic stress is capable of exacerbating each major, modifiable, endogenous risk factor for cerebrovascular and cardiovascular disease. Indeed, exposure to stress can increase both the incidence and severity of stroke, presumably through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Now that characterization of the mechanisms underlying epigenetic programming of the HPA axis is well underway, there has been renewed interest in examining the role of early environment on the evolution of health conditions across the entire lifespan.

Moderate recurrent hypoglycemia during early development leads to persistent changes in affective behavior in the rat.

Recurrent hypoglycemia is a common problem among infants and children that is associated with several metabolic disorders and insulin-dependent diabetes mellitus. Although studies have reported a relationship between a history of juvenile hypoglycemia and psychological health problems, the direct effects of recurrent moderate hypoglycemia have not been fully determined. Thus, in this study, we used an animal model to examine the effects of recurrent hypoglycemia during the juvenile period on affective, social, and motor function (assessed under euglycemic conditions) across development.

2006 Curt P. Richter award winner: Social influences on stress responses and health.

Both positive and negative social interactions can modulate the hypothalamic-pituitary-adrenal (HPA) axis and influence recovery from injuries and illnesses, such as wounds, stroke, and cardiac arrest. Stress exacerbates neuronal death following stroke and cardiac arrest, and delays cutaneous wound healing, via a common mechanism involving stress-induced increases in corticosterone, acting on glucocorticoid receptors. In contrast, hamsters and mice that form social bonds are buffered against stress and heal cutaneous wounds more quickly than socially isolated animals, presumably because the physical contact experienced by the pairs releases oxytocin, which in turn suppresses the HPA axis and facilitates wound healing.

Role of IL-1 in poststroke depressive-like behavior in mice.

Background: Poststroke depression (PSD) leads to impaired functional recovery and increased mortality, yet physiological mechanisms are unknown. The present study investigates the roles of glucocorticoids and interleukin-1 (IL-1) in poststroke anhedonia.

Methods: Adult male mice underwent middle cerebral artery occlusion (MCAO), and were recovered 7 days.

Neonatal factors influence adult stroke outcome.

Neonatal environment can have important, life-long influences on stress-reactivity and hypothalamic-pituitary-adrenal (HPA) axis regulation. In rodents, brief mother-infant separations have been shown to improve efficiency of the HPA axis, decrease stress-reactivity, and decrease age-related declines in cognitive function. Here, we provide evidence that there are potential costs associated with improved HPA axis regulation, including increased sensitivity to cerebral inflammation and glucocorticoid-mediated neuronal death following stroke.

Neuroprotective properties of the natural vitamin E alpha-tocotrienol.

Background And Purpose: The current work is based on our previous finding that in neuronal cells, nmol/L concentrations of alpha-tocotrienol (TCT), but not alpha-tocopherol (TCP), blocked glutamate-induced death by suppressing early activation of c-Src kinase and 12-lipoxygenase.

Methods: The single neuron microinjection technique was used to compare the neuroprotective effects of TCT with that of the more widely known TCP. Stroke-dependent brain tissue damage was studied in 12-Lox-deficient mice and spontaneously hypertensive rats orally supplemented with TCT.

Social interaction improves experimental stroke outcome.

Background And Purpose: Social interaction can have a profound effect on health. The purpose of the present study was to determine whether affiliative social interactions before and after stroke improve ischemic outcomes as assessed through histological analysis and behavioral assays.

Methods: Male and female C57BL/6 mice were housed individually or with an ovariectomized female.

Microsphere embolism-induced cortical cholinergic deafferentation and impairments in attentional performance.

Ischemic events have been hypothesized to play a critical role on the pathogenesis of dementia and the acceleration of cognitive impairments. This experiment was designed to determine the consequences of microvascular ischemia on the cortical cholinergic input system and associated attention capacities. Injections of microspheres ( approximately 50 microm diameter; approximately 5000 microspheres/100 microL) into the right common carotid artery of rats served as a model of microvascular ischemia and resulted in decreases in the density of cholinergic fibers in the ipsilateral medial prefrontal cortex and frontoparietal areas.

Social facilitation of wound healing.

It is well documented that psychological stress impairs wound healing in humans and rodents. However, most research effort into influences on wound healing has focused on factors that compromise, rather than promote, healing. In the present study, we determined if positive social interaction, which influences hypothalamic-pituitary-adrenal (HPA) axis activity in social rodents, promotes wound healing.