Biomedical subjects

Tara K S Craft

Publications and source records attributed to Tara K S Craft.

6 recordsLinked to original sources

PubMed2006

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. Mice were treated with metyrapone (100 mg/kg intraperitoneally), mifepristone (50 mg/kg subcutaneously), or vehicle injections on reperfusion days 4-7. A separate cohort of mice was implanted with cannulae and was administered IL-1 receptor antagonist (IL-1ra) or vehicle (6 microg intracerebroventricularly) on reperfusion days 6 and 7. After the final injection or infusion, sucrose consumption was recorded for 6 hours. RESULTS: Mice in the sham-treated group consumed significantly more sucrose solution than water, whereas MCAO-treated mice consumed similar amounts of each, suggesting anhedonia among MCAO-treated mice. A separate experiment assessed whether stroke-induced increases in corticosteroids or IL-1 contribute to anhedonia. Only IL-1ra restored sucrose consumption in MCAO-treated mice. Vehicle-MCAO-treated mice drank significantly less sucrose solution than did both IL-1ra and vehicle-sham treatment groups, whereas IL-1ra-MCAO-treated mice drank similar amounts to both sham-treated groups. CONCLUSIONS: Poststroke anhedonia, a symptom of depression in human beings, can be reproduced in a mouse model of stroke and appears to involve altered IL-1 transmission in the brain.

Animals↗

PubMed2006

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. Specifically, brief mother-infant separation decreases the initial corticosteroid response to experimental stroke in adult mice, but increases post-stroke pro-inflammatory cytokine expression, edema, and infarct volume compared to ischemic controls. Brief maternal separation also compromises functional recovery and long-term survival following stroke. In addition, adrenalectomy reverses the effects of brief maternal separation on stroke outcome when corticosterone is replaced at baseline, but not ischemic, concentrations; thus, neonatally separated mice are more sensitized as adults to the detrimental effects of elevated corticosterone during ischemia. Taken together, these data provide the first direct evidence that neonatal environment can substantially influence adult cerebrovascular health.

Adrenal Glands↗

PubMed2005

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. RESULTS: Subattomole quantity of TCT, but not TCP, protected neurons from glutamate challenge. Pharmacological as well as genetic approaches revealed that 12-Lox is rapidly tyrosine phosphorylated in the glutamate-challenged neuron and that this phosphorylation is catalyzed by c-Src. 12-Lox-deficient mice were more resistant to stroke-induced brain injury than their wild-type controls. Oral supplementation of TCT to spontaneously hypertensive rats led to increased TCT levels in the brain. TCT-supplemented rats showed more protection against stroke-induced injury compared with matched controls. Such protection was associated with lower c-Src activation and 12-Lox phosphorylation at the stroke site. CONCLUSIONS: The natural vitamin E, TCT, acts on key molecular checkpoints to protect against glutamate- and stroke-induced neurodegeneration.

Animals↗

PubMed2005

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. Behavioral assessments were made 24 hours before 60 or 90 minutes of transient intraluminal middle cerebral artery occlusion (MCAO) or SHAM surgery and after 7 days of reperfusion. Two hours after behavioral testing on day 7, infarct size was determined by 2,3,5-triphenyltetrazolium histology, and blood samples were collected for assessment of corticosterone and C-reactive protein (CRP) concentrations. RESULTS: Pair housing significantly decreased infarct size and improved contralateral paw use in 60-minute MCAO males and 90-minute MCAO females compared with socially isolated cohorts. Housing condition had no significant effect on infarct size in females that underwent 60 minutes of MCAO, but pair housing was associated with improved contralateral paw use relative to socially isolated mice. In a separate cohort of males, intraischemic CRP concentration was significantly reduced in pair-housed males relative to isolated males. CONCLUSIONS: Affiliative interaction during the peri-ischemic period reduces intraischemic CRP concentration, decreases ischemic damage in male and female mice, and improves behavioral outcome.

Animals↗

PubMed2005

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. Furthermore, dense astrogliosis, indicated by glial fibrillary acidic protein (GFAP) immunohistochemistry, was observed in the globus pallidus, including the areas of origin of cholinergic projections to the cortex. Fluoro-Jade B staining indicated that loss of neurons in the cortex was restricted to areas of microsphere-induced infarcts. Attentional performance was assessed using an operant sustained attention task; performance in this task was previously demonstrated to reflect the integrity and activity of the cortical cholinergic input system. Embolized animals' performance was characterized by a decrease in the animals' ability to detect signals. Their performance in non-signal trials remained unaffected. The residual density of cholinergic axons in prefrontal and frontoparietal areas correlated with the animals' performance. The present data support the hypothesis that microvascular ischemia results in loss of cortical cholinergic inputs and impairs associated attentional performance. Microsphere embolism represents a useful animal model for studying the role of interactions between microvascular disorder and impaired forebrain cholinergic neurotransmission in the manifestation of cognitive impairments.

Acetylcholine↗

PubMed2004

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. Siberian hamsters received a cutaneous wound and then were exposed to immobilization stress. Stress increased cortisol concentrations and impaired wound healing in isolated, but not socially housed, hamsters. Removal of endogenous cortisol via adrenalectomy eliminated the effects of stress on wound healing in isolated hamsters. Treatment of isolated hamsters with oxytocin (OT), a hormone released during social contact and associated with social bonding, also blocked stress-induced increases in cortisol concentrations and facilitated wound healing. In contrast, treating socially housed hamsters with an OT antagonist delayed wound healing. Taken together, these data suggest that social interactions buffer against stress and promote wound healing through a mechanism that involves OT-induced suppression of the HPA axis. The data imply that social isolation impairs wound healing, whereas OT treatment may ameliorate some effects of social isolation on health.

Analysis of Variance↗