Biomedical subjects

Hubert J Bardenheuer

Publications and source records attributed to Hubert J Bardenheuer.

8 recordsLinked to original sources

PubMed2006

Chronic corticosterone-induced deterioration in rat behaviour is not paralleled by changes in hippocampal NF-kappaB-activation.

We investigated whether long-lasting stress induced by chronic glucocorticoid (GC) exposure affects activation of brain NF-kappaB and whether these changes are related to functional deterioration and structural changes in the rat hippocampus. Psychometric investigations were conducted using a holeboard test system in 28 one-year-old male Wistar rats. Thereafter, rats were divided into three groups for daily administration of 10 mg corticosterone (treatment) or sesame oil (placebo = sham control for effects of the vehicle) for 60 days. Additional control rats did not receive any treatment or handling until the end of the experiment. Behavioural and cognitive changes were tested again in the holeboard system. Rat body weights and corticosterone concentrations in plasma, hippocampus and urine were determined and adrenal glands were investigated histopathologically. Hippocampal concentrations of corticosterone, NF-kappaB and I-kappaBalpha were determined using RIA, EMSA and Western blotting techniques, respectively. Structural changes in rat hippocampus were measured using magnetic resonance imaging techniques. High peripheral corticosterone concentrations after chronic treatment led to significant reductions in rat body weight. Significant atrophy of both adrenal glands with marked histological deterioration was detected. Furthermore, an increase in hippocampal corticosterone concentrations was observed after chronic administration. Chronic corticosterone treatment also significantly altered behaviour and working and reference memory capacity without changing hippocampal structure. Daily injections of sesame oil in the placebo group, however, were also sufficient to reduce the pellet-finding time. However, neither in the corticosterone group nor in the placebo group were behavioural changes paralleled by significant changes in brain NF-kappaB activation and I-kappaBalpha expression. Thus, cognitive alterations in rats seen after chronic corticosterone exposure are not paralleled by hippocampal NF-kappaB modulation.

Animals↗

PubMed2005

Evolution of apparent diffusion coefficient and transverse relaxation time (T2) in the subchronic stage of global cerebral oligemia in different rat models.

Using magnetic resonance imaging techniques, we examined the time course of apparent diffusion coefficient (ADC), T2, and T2* relaxation times in 1-year-old rats after different forms of cerebral oligemia had been induced by (1) transient systemic hypotension, (2) permanent bilateral carotid artery occlusion (BCCAO), and (3) combined hypotension and BCCAO over a time period of 14 days after the oligemic event. These groups were compared with a group of sham-operated adult rats (controls, 4) to rule out a drift of the parameters over time. The animals were examined in a 2.35 T scanner. ADC, T2, and T2* were measured in both hemispheres of rat parietotemporal cerebral cortex, thalamic nuclei, and hippocampus 1 day before as well as on days 1, 3, 7, and 14 after sham operation and in different models of oligemia, respectively. Hypotension alone had no significant effect on MRI parameters in rat brain. After BCCAO, an increase in T2* was observed. If a permanent BCCAO was combined with transient hypotension, however, 84% of 1-year-old animals died within 14 days after surgery. In the surviving animals, significant changes in ADC, T2, and T2* were observed in the hippocampus and parietotemporal cerebral cortex. ADC showed a decrease on day 1 after oligemia, and an increase on days 3, 7, and 14. The T2* and T2 values were markedly increased on days 7 and 14 after surgery. In conclusion, only severe oligemia combining BCCAO and hypotension induces significant changes in tissue integrity (as shown by ADC) and in blood oxygenation levels in the subchronic period, whereas no significant changes were detected if permanent BCCAO or transient hypotension was applied separately.

Analysis of Variance↗

PubMed2005

Hypoxia impairs systemic endothelial function in individuals prone to high-altitude pulmonary edema.

RATIONALE: High-altitude pulmonary edema (HAPE) is characterized by excessive pulmonary vasoconstriction and is associated with decreased concentrations of nitric oxide (NO) in the lung. OBJECTIVES: We hypothesized that individuals susceptible to HAPE (HAPE-S) would also have dysfunction of the vascular NO vasodilator pathway during hypoxia in the systemic vasculature. METHODS: During normoxia (FI(O(2)) = 0.21) and 4 hours of normobaric hypoxia (FI(O(2)) = 0.12, corresponding to an altitude of 4,500 m above sea level) endothelium-dependent and endothelium-independent vasodilator responses to intraarterial infusion of acetylcholine (ACh) and sodium nitroprusside, respectively, were measured by forearm venous occlusion plethysmography in nine HAPE-S subjects and in nine HAPE-resistant control subjects. MAIN RESULTS: Pulmonary artery systolic pressure increased from 22 +/- 3 to 33 +/- 6 mm Hg (p < 0.001) during hypoxia in control subjects, and from 25 +/- 4 to 50 +/- 9 mm Hg in HAPE-S subjects (p < 0.001). Despite similar responses during normoxia in both groups, ACh-induced changes in forearm blood flow markedly decreased during hypoxia in HAPE-S subjects (p = 0.01) but not in control subjects. The attenuated vascular response to ACh infusion during hypoxia inversely correlated with increased pulmonary artery systolic pressure (p = 0.04) and decreased plasma nitrite correlated with attenuated ACh-induced vasodilation in HAPE-S subjects (p = 0.02). CONCLUSIONS: Hypoxia markedly impairs vascular endothelial function in the systemic circulation in HAPE-S subjects due to a decreased bioavailability of NO. Impairment of the NO pathway could contribute to the enhanced hypoxic pulmonary vasoconstriction that is central to the pathogenesis of HAPE.

Acetylcholine↗

PubMed2004

A mouse model of cerebral oligemia: relation to brain histopathology, cerebral blood flow, and energy state.

An animal model involving stepwise occlusion of the common carotid arteries (sCCAO) in DBA/2 mice is presented in which the right and left carotid arteries were permanently ligated within a time interval of four weeks. Thereafter, cerebral functional and structural parameters were determined at acute (15 min) and subchronic (1 day; 3, 7, and 14 days) time points after sCCAO. Quantitative changes in regional cerebral blood flow (rCBF) as determined by the [14C]iodoantipyrine method, energy state (ATP, phosphocreatine, ADP, AMP, adenosine) as shown by HPLC, brain histopathology, and neuronal densities were measured in both hemispheres. Acute sCCAO was accompanied by a drastic reduction in cerebral energy-rich phosphate concentrations, ATP and phosphocreatine, and in rCBF of more than 50%. In contrast, cortical adenosine increased around five-fold. Subchronic sCCAO, however, was associated with normalization in brain energy metabolites and near-complete restoration of rCBF, except in the caudate nucleus (-40%). No marked signs of necrotic or apoptotic cell destruction were detected. Thus, during the subchronic period, compensatory mechanisms are induced to counteract the drastic changes seen after acute vessel occlusion. In conclusion, this sCCAO mouse model may be useful for long-lasting investigations of stepwise deterioration contributing to chronic cerebrovascular disorders.

Adenosine↗

PubMed2004

The systemic inflammatory response syndrome.

Sepsis and septic shock are the leading causes of death in intensive care units in developed countries despite recent advances in critical care medicine. Sepsis is the systemic inflammatory response to infection frequently associated with hypoperfusion followed by tissue injury and organ failure. The activation of monocytes/macrophages and neutrophils, with the consecutive release of pro-inflammatory mediators and activation of the coagulation cascade, seems to play a key role in the pathogenesis of sepsis. Elimination of the septic focus, anti-microbial therapy and supportive treatment are the cornerstones of sepsis therapy. In addition, the application of small doses hydrocortisone to patients with refractory septic shock and the treatment of patients with septic multiple organ failure with activated protein C are two adjunctive therapeutic strategies. Promising new experimental treatment options are interference with MIF, HMGB1, C5a or TREM-1 signal transduction pathways and an inhibition of apoptosis, which may further improve the prognosis of septic patients in the future.

Animals↗

PubMed2004

Regional cerebral oxygen saturation is a sensitive marker of cerebral hypoperfusion during orthotopic liver transplantation.

Neurological complications contribute significantly to morbidity and mortality of patients after orthotopic liver transplantation (OLT). One possible cause of postoperative neurological complications is cerebral ischemia during the surgical procedure. In this study, we investigated the relationship between intraoperative changes in regional cerebral oxygen saturation (rSo(2)) and postoperative values of neuron-specific enolase (NSE) and S-100, which are specific variables that indicate cerebral disturbances due to hypoxia/ischemia. The rSo(2) was monitored continuously by near-infrared spectroscopy in 16 patients undergoing OLT. In addition, NSE and S-100 were determined in arterial blood before surgery and 24 h after reperfusion of the donor liver. Interestingly, clamping of the recipient's liver led to a significant decline in rSo(2) in eight patients, whereas the others tolerated clamping without major changes in rSo(2). The decrease in rSo(2) after clamping correlated significantly with postoperative increases in NSE (r(2) = 0.57) and S-100 (r(2) = 0.52). However, there were no significant differences between patients with and without rSo(2) decline concerning hemodynamic variables. There were no significant correlations between DeltarSo(2) and cardiac output (r(2) = 0.20), NSE and cardiac output (r(2) = 0.37), or S-100 and cardiac output (r(2) = 0.24). Monitoring of rSo(2) may be a useful noninvasive tool to estimate disturbances in rSo(2) during OLT.

Adult↗

PubMed2002

In vivo monitoring of age-related changes in rat brain using quantitative diffusion magnetic resonance imaging and magnetic resonance relaxometry.

Diffusion-weighted magnetic resonance imaging (MRI) has been proven to be a sensitive diagnostic tool to examine age associated acute and chronic changes in brain tissue. The aim of our study was to examine whether there are differences in brain diffusion and transverse relaxation time between young and adult rats. In an experimental MR scanner, 24 young (age: 3 months) and 26 adult rats (age: 12 months) were examined using diffusion-weighted and transverse relaxation time (T2)-weighted MRI sequences. There were no differences in the T2 relaxation time between the two animal groups, either local or global. However, the mean apparent diffusion coefficient (ADC) within the whole brain was significantly lower (P<0.0005) in the adult animals (765+/-35 x 10(-6) mm(2)/s) than in the young animals (829+/-45 x 10(-6) mm(2)/s). ADC decrease was mainly found in the cerebral cortex. These results can be attributed to an activity-related or central nervous system damage-related internal water shift from the extracellular to the intracellular space without a net increase in water content in brain tissue. Our study also shows that age-related changes in diffusion should be considered when performing longitudinal studies in rats.

Aging↗

PubMedDate not supplied

Does permanent carotid artery occlusion produce a 'preconditioning-like' effect towards more severe hypotension in energy metabolites? Role of cerebral adenosine.

1. The aim of the present study was to investigate the potential energy preserving effect of permanent bilateral common carotid artery occlusion (BCCAO) towards additional systemic hypotension of severe duration (30 min). In addition, the role of adenosine A1 receptors in cerebral ischaemic preconditioning was investigated in male Wistar rats. Thus, oligaemic rats were assigned randomly to continuous treatment with the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) or the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT), receiving daily intraperitoneal infusions of 0.1 mg/kg bodyweight CCPA or CPT or placebo (200 microL aqueous 2-hydropropyl-beta-cyclodextrin) at a delivery rate of 0.5 microL/h over 14 days. 2. Haemodynamic parameters and arterial blood gases were monitored. Rat cortical energy metabolites ATP, ADP, AMP, phosphocreatine and adenosine were measured using HPLC techniques. Adenosine A1 receptor expression was determined by immunhistochemistry and quantified by western blotting. 3. Two weeks of permanent BCCAO induced an 'energy saving' effect in rat cortical ATP concentrations. Under subchronic conditions, significant increases were detected in ADP and AMP concentrations after CCPA compared with placebo. Because similar changes were also seen after CPT, this adenosine A1 receptor-mediated effect does not seems to be specific. Furthermore, no differences in adenosine A1 receptor expression could be detected. 4. Adenosine was not specifically involved in the 'preconditioning-like' effect via the modulation of the adenosine A1 receptor in the present oligaemia model. Obviously, adenosine A1 receptor-specific effects after delayed cerebral ischaemic preconditioning do not seem to play an essential role if BCCAO is followed by a prolonged additional severe ischaemic event.

Adenine Nucleotides↗