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A Courtney DeVries

Publications and source records attributed to A Courtney DeVries.

13 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↗
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

Cardiac arrest/cardiopulmonary resuscitation augments cell-mediated immune function and transiently suppresses humoral immune function.

Immune system activation has implications for cerebrovascular health, but little is known about the function of the immune system after a major cerebrovascular event, such as cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Cardiac arrest and cardiopulmonary resuscitation damages the hippocampus, an important component of the hypothalamic-pituitary-adrenal (HPA) axis, and alterations in HPA axis activity can affect immune function. We tested the hypothesis that CA/CPR (approximately 8 mins) would cause HPA axis dysregulation and alter the delayed type hypersensitivity (DTH) response to antigenic challenge. We also assessed the primary and secondary antibody response of mice exposed to CA/CPR. Of the mice exposed to CA/CPR, half had brains protected by hypothermia to isolate the effects of the CA/CPR procedure from the effects of CA/CPR-induced neuronal damage. Cardiac arrest and cardiopulmonary resuscitation-induced neuronal damage resulted in a persistent elevation of blood corticosterone concentration and a concomitant augmentation of the DTH response to antigenic challenge. Furthermore, immune activation before CA/CPR decreased survival after global ischemia. These data highlight the potential impact of neuronal damage on cell-mediated immune function and the role of humoral immune activation in outcome after global ischemia.

Animals↗
PubMed2004

Histopathological and behavioral characterization of a novel model of cardiac arrest and cardiopulmonary resuscitation in mice.

Cardiac arrest is associated with high mortality and poor neurological outcome. We characterized functional and histological outcome in a novel mouse model of cardiac arrest and cardiopulmonary resuscitation (CPR) in order to study neuroprotective mechanisms. Cardiac arrest was induced in male C57Bl/6 and 129SVEV mice by i.v. injection of KCl. After 10 min cardiac standstill, CPR was initiated by administration of epinephrine, ventilation with 100% oxygen and chest compressions. Twenty-four hours before and 3 or 7 days after CPR, mice were subjected to behavioral testing using a passive avoidance task, locomotor activity in an open field, and spontaneous alternation in a T-maze. Hippocampal and caudoputamen injury was quantified 3 or 7 days after CPR. At both time points, caudoputamen injury was worse in 129SVEV mice. Post-ischemic mice of both strains showed a reduced number of correct choices in the T-maze up to 7 days after CPR, and were temporarily impaired in learning the passive avoidance task with a retention deficit on day 3 but not on day 7. Locomotor activity showed strain differences with C57Bl/6 mice being more active, but little ischemia-related effects. A dissociation between functional and histological outcome was found emphasizing the importance of combining both outcome measures for evaluation of neuroprotective strategies.

Animals↗
PubMed2004

Chronic behavioral testing after focal ischemia in the mouse: functional recovery and the effects of gender.

Several useful behavioral tests exist for measuring behavioral recovery after ischemia in higher-order animals and rats. With the increasing use of mice in focal stroke research, simple, reliable, and reproducible behavioral testing has become a priority. As neuroprotective agents are tested, long-term outcome must be assessed, especially in studies focused on neuronal plasticity and regeneration after ischemia. Our laboratory and others have previously shown that estrogen (E2) is neuroprotective in rodent stroke paradigms. We examined a battery of behavioral tests in male and female mice subjected to 90 min of middle cerebral artery occlusion (MCAO) to determine the most sensitive tests for detecting sensorimotor dysfunction after stroke, and to determine the functional significance of E2-mediated neuroprotection. Only two tests, the corner test and the cylinder test, were able to differentiate between groups (sham and stroke) after several days of repeated testing. The cylinder test was sensitive to the neuroprotective/neurorestorative effects of E2, but 2 weeks after stroke, the cylinder test was unable to distinguish between sham and stroke animals treated with E2. In contrast, the corner test was able to differentiate stroke and sham animals even 6 weeks after stroke, but did not distinguish animals treated with E2 vs. vehicle. These tests provide a simple, rapid, reliable assessment of sensorimotor dysfunction in the mouse after focal ischemia. Hormonal status influences speed of recovery on cylinder testing in animals of both genders. This suggests that a short battery of tests including the neurological score, cylinder, and corner test may be adequate to rapidly and repeatedly assess sensorimotor dysfunction in mice of both genders.

Animals↗
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↗
PubMed2004

Cardiac arrest/cardiopulmonary resuscitation increases anxiety-like behavior and decreases social interaction.

Advances in medical technology have increased the number of individuals who survive cardiac arrest/cardiopulmonary resuscitation (CPR). This increased incidence of survival has created a population of patients with behavioral and physiologic impairments. We used temperature manipulations to characterize the contribution of central nervous system damage to behavioral deficits elicited by 8 minutes of cardiac arrest/CPR in a mouse model. Once sensorimotor deficits were resolved, we examined anxiety-like behavior with the elevated plus maze and social interaction with an ovariectomized female. We hypothesized that anxiety-like behavior would increase and social interaction would decrease in mice subjected to cardiac arrest/CPR and that these changes would be attributable to central nervous system damage rather than damage to peripheral organs or changes orchestrated by the administration of epinephrine. Mice that were subjected to cardiac arrest/CPR while the peripheral organs, but not the brain, were protected by hypothermia exhibited increased anxiety-like behavior and decreased social interaction, whereas mice with hypothermic brains and peripheral organs during cardiac arrest/CPR did not exhibit behavioral impairments. The present study demonstrates that central nervous system damage from cardiac arrest/CPR results in increased anxiety and decreased social interaction and that these behavioral changes are not attributed to underlying sensorimotor deficits, dynamics of arrest and CPR, or peripheral organ damage.

Animals↗
PubMed2004

Cardiac arrest with cardiopulmonary resuscitation reduces dendritic spine density in CA1 pyramidal cells and selectively alters acquisition of spatial memory.

The hippocampus is highly sensitive to ischemia and is one of the most extensively damaged regions of brain during cardiac arrest. Damage to hippocampus can subsequently lead to learning and memory deficits. The current study used the Morris water maze to characterize spatial learning and memory deficits elicited by 8 min of cardiac arrest with cardiopulmonary resuscitation (CA/CPR) in mice, which is associated with a 25-50% decrease in CA1 neurons. Mice were trained to navigate the water maze prior to CA/CPR or sham surgery (SHAM). They were retested in the water maze on days 7 and 8 postsurgery; both CA/CPR and SHAM groups were able to perform the task at presurgical levels. However, when the hidden platform was moved to a new location, the SHAM mice were able to adapt more quickly to the change and swam a shorter distance in search of the platform than did CA/CPR mice. Thus, CA/CPR did not affect the ability of mice to retain a previously learned platform location, but it did affect their ability to learn a new platform location. This behavioural impairment was correlated with dendritic spine density in the CA1 region of the hippocampus. Data presented here suggest that morphological changes, such as spine density, that occur in neurons that survive CA/CPR may be associated with cognitive impairments.

Animals↗
PubMed2003

Social modulation of stress responses.

Social interactions can profoundly affect the hypothalamic-pituitary-adrenal (HPA) axis. Although most research on social modulation of glucocorticoid concentrations has focused on the consequences of exposure to stressful social stimuli, there is a growing body of literature which suggests that social support in humans and affiliative behaviors in some animals can provide a buffer against stress and have a positive impact on measures of health and well-being. This review will compare HPA axis activity among individuals for whom social relationships are maintained through aggressive displays, such as dominance hierarchies, vs. individuals engaging in high levels of prosocial behavior. We also will examine oxytocin, a neuropeptide that is well known for promoting social behavior, as the physiological link between positive social interactions and suppression of the HPA axis. Despite many examples of social interaction modulating the HPA axis and improving health outcomes, there is relatively little known regarding the underlying mechanisms through which social behavior can provide a buffer against stress-related disease.

Adaptation, Physiological↗
PubMed2002

Corticotropin-releasing factor induces social preferences in male prairie voles.

Exposure to stressors facilitates the formation of social preferences in monogamous male prairie voles (Microtus ochrogaster). In the present study, the hypothesis was tested that treatment with corticotropin-releasing factor (CRF), a neuropeptide released during stress, is capable of inducing social preferences in male prairie voles. The effects of five doses of CRF (0.01, 0.1, 1.0, 10 and 100 ng; i.c.v.) on social preference were assessed. Exogenous CRF did not alter the amount of social contact that occurred between the experimental animal and partner during the initial cohabitation period. However, when tested after 3 h of cohabitation, animals that had been treated with 0.1 or 1.0 ng CRF spent significantly more time in physical contact with the partner than a stranger. In contrast, 3 h of cohabitation was not sufficient to induce social preferences in animals pre-treated with an artificial CSF vehicle or other doses of CRF. Furthermore, co-administration of a CRF receptor antagonist prevented the formation of CRF-induced social preferences. These data provide support for a role of the hypothalamic-pituitary-adrenal axis in social bonding in prairie voles.

Animals↗
PubMed2002

Social stress exacerbates focal cerebral ischemia in mice.

BACKGROUND AND PURPOSE: The purpose of the present study was to determine whether exposure to stress or elevated corticosterone concentrations in the days preceding cerebral ischemia exacerbates ischemic injury as assessed by histological and behavioral outcomes. METHODS: For 7 consecutive days, male C57/BL6 mice were exposed to social stress for 45 minutes or injected with 1 mg/kg corticosterone or vehicle. The animals exposed to social stress were injected with either 1 mg/kg mifepristone, a glucocorticoid receptor antagonist, or the vehicle 30 minutes before stress. On the seventh day, all animals were trained in a passive avoidance task. Twenty-four hours after training, the animals were subjected to 60 minutes of intraluminal middle cerebral artery occlusion (MCAO) or sham surgery. At 72 hours of reperfusion, the animals were tested for retention of the passive avoidance task, and infarction size was determined. RESULTS: Animals subjected to chronic social stress or treated with exogenous corticosterone before MCAO exhibited larger infarcts and reduced retention of passive avoidance compared with the nonstressed MCAO control. The effects of social stress on infarct volume and passive avoidance were reversed by pretreatment with mifepristone. There was no difference between stressed and control groups in physiological parameters or reduction of laser-Doppler flow signal during MCAO or reperfusion. CONCLUSIONS: Prior exposure to social stress increases infarction volume and exacerbates cognitive deficits associated with transient cerebral ischemia. The mechanism underlying the effects of stress on stroke outcome likely involves corticosterone acting through glucocorticoid receptors to increase subsequent ischemia-induced neuronal death.

Animals↗