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Reinhard Bauer

Publications and source records attributed to Reinhard Bauer.

32 records · Page 2Linked to original sources
PubMed2004

Pathophysiology of traumatic injury in the developing brain: an introduction and short update.

Current understanding about the main peculiarities in pathophysiology of immature brain traumatic injury involves marked developmental discrepancy of biomechanical properties, aspects of altered features in water and electrolyte homeostasis as well as maturation dependent differences in structural and functional responses of major transmitter systems. Based on the fact that traumatic brain injury (TBI) is one of the major causes of morbidity and mortality in infants and children, the currently available epidemiological data are reviewed in order to gain insights about scope and dimension of health care engagement and derive the requirements for reinforced pathogenetic research. To this end, the main aspects of peculiarities in primary and secondary TBI mechanisms in the immature/developing brain are discussed, including structural and functional conditions resulting in a markedly diminished shear resistance of the immature brain tissue. As such, the immature brain tissue appears to be more susceptible to mechanical alterations, because similar mechanical load induces a more intense brain tissue displacement. Furthermore, available indications for increased incidence of brain swelling in the immature brain after TBI are reviewed, focusing on the interrelationship between the age-dependent differences in extracellular space and aquaporin-4 expression during brain maturation. The developmental differences of TBI induced cerebrovascular response as well as some relevant aspects of altered neurotransmission following TBI of the immature brain in regard to the glutamatergic and dopaminergic transmitter system are assessed. Thus, this mini-review highlights some progress but also an increased necessity for expanded pathogenetic research on a clinical scale in order to develop a solid foundation for adequate therapeutic strategies for the different life-threatening consequences of TBI in infancy and childhood, which mainly have failed up to now.

Age Factors↗
PubMed2004

Stupor and coma: pathophysiology of hypoxia--ontogenetic aspects.

There are several levels of O2 deprivation with different possibilities of adaptation and compensation. All of them appear to be highly conservative in phylogenesis and are active early in ontogenetic development. The coordinated structural and functional responses to systemic and/or local hypoxia form the basis for individual adaptation to environmental requirements and pathological threat.

Adaptation, Physiological↗
PubMed2004

Age-dependent effects of severe traumatic brain injury on cerebral dopaminergic activity in newborn and juvenile pigs.

There is evidence that the dopaminergic system is sensitive to traumatic brain injury (TBI). However, the age-dependency of this sensitivity has not been studied together with brain oxidative metabolism. We postulate that the acute effects of severe TBI on brain dopamine turnover are age-dependent. Therefore 18F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with Positron-Emission-Tomography (PET) was used to estimate the activity of the aromatic amino acid decarboxylase (AADC) in the brain of 11 newborn piglets (7-10 days old) and nine juvenile pigs (6-7 weeks old). Six newborn and five juvenile animals were subjected to a severe fluid-percussion (FP) induced TBI. The remaining animals were used as sham operated untreated control groups. Simultaneously, the regional cerebral blood flow (CBF) was measured with colored microspheres and the cerebral metabolic rates of oxygen and glucose were determined. At 1 h after FP-TBI, [18F]FDOPA was infused and PET scanning was performed for 2 h. At 2 h after FP-TBI administration, a second series of measurements of physiological values including CBF and brain oxidative metabolism data had been obtained. Severe FP-TBI elicited a marked increase in the rate constant for fluorodopamine production (k3FDOPA) in all brain regions of newborn piglets studied by between 97% (mesencephalon) and 143% (frontal cortex) (p < 0.05). In contrast, brain hemodynamics and cerebral oxidative metabolism remained unaltered after TBI. Furthermore, the permeability-surface area product of FDOPA (PSFDOPA) was unchanged. In addition, regional blood flow differences between corresponding ipsi- and contralateral brain regions did not occur after TBI. Thus, it is suggested that severe FP-TBI induces an upregulation of AADC activity of newborn piglets that is not related to alterations in brain oxidative metabolism.

Age Factors↗
PubMed2004

Secondary injuries in brain trauma: effects of hypothermia.

Hypothermia has been shown to be cerebroprotective in traumatized brains. Although a large number of traumatic brain injury (TBI) studies in animals have shown that hypothermia is effective in suppressing a variety of damaging mechanisms, clinical investigations have shown less consistent results. The complexity of damaging mechanisms in human TBI may contribute to these discrepancies. In particular, secondary injuries such as hypotension and hypoxemia may promote poor outcome. However, few experimental TBI studies have employed complex models that included such secondary injuries to clarify the efficacy of hypothermia. This review discusses the effects of hypothermia in various TBI models addressing primary and acute secondary injuries. Included are recently published clinical data using hypothermia as a therapeutic tool for preventing or reducing the detrimental posttraumatic secondary injuries and neurobehavioral deficits. Also discussed are recent successful applications of hypothermia from outside the TBI realm. Based on all available data, some general considerations for the application of hypothermia in TBI patients are given.

Animals↗
PubMed2003

Marked reduction of brainstem blood flow in artificially ventilated newborn piglets during normoxia and normocapnic hypoxia.

OBJECTIVE: To estimate the effect of artificial ventilation on regional cerebral blood flow, cardiovascular regulation, and cerebral oxidative metabolism in newborns. DESIGN AND SUBJECTS: Comparison of three randomized treatment groups of newborn piglets: Group 1 (artificially ventilated sham-operated group; n =7); group 2 (artificially ventilated group with normoxia and moderate normocapnic hypoxia; n =7); group 3 (spontaneously breathing group with normoxia and moderate normocapnic hypoxia; n =6). MEASUREMENTS AND RESULTS: Animals were anesthetized with 0.5% isoflurane in 70% nitrous oxide and 30% oxygen. Groups 1 and 2 were artificially ventilated. Animals in group 3 breathed spontaneously. Moderate normocapnic hypoxia was induced in groups 2 and 3 for 1 h by lowering the inspiratory oxygen fraction from 0.35 to 0.11. Mode of ventilation induced at most marginal effects on global cerebrovascular response, cardiovascular regulation, and cerebral oxidative metabolism. However, under normoxic conditions, regional cerebral blood flow of the medulla oblongata, pons, mesencephalon, thalamus, and cerebellum were markedly reduced in artificially ventilated piglets ( P <0.05). Moderate normocapnic hypoxia led to a marked increase in regional cerebral blood flow, which was significantly lower in the medulla oblongata, pons, mesencephalon, thalamus, and cerebellum of artificially ventilated piglets ( P <0.05). CONCLUSION: Artificial ventilation clearly induces reduced neuronal activity in the brain stem and cerebellum of newborn piglets. This is suggested by a considerably reduced blood flow in these regions under normoxia and moderate normocapnic hypoxia. However, there is no relevant detrimental effect on cardiovascular regulation and brain oxidative metabolism.

Animals↗
PubMed2003

Impact of asymmetric intrauterine growth restriction on organ function in newborn piglets.

Fetal malnutrition may induce asymmetric intrauterine growth restriction (aIUGR) with long-lasting consequences. Understanding the organ-specific structural and functional effects aIUGR may have on the newborn, and understanding the potential impact on the neonatal response to compromising conditions, appears to be essential for adequate treatment. Therefore, a survey is given of some organ-specific alterations in newborns, which have suffered from aIUGR. We studied these effects in a model of asymmetric intrauterine growth restriction based on the spontaneous occurrence of runting in pigs. We wish to demonstrate that experimental studies in animal models are necessary and helpful to elucidate pathogenetic mechanisms. aIUGR seems to have both beneficial and detrimental effects on the newborn. The development of skeletal muscles (conversion to oxidative type I fibers) and of their vascular supply as well as of the brain dopaminergic activity is accelerated. Also, aIUGR apparently improves the ability to withstand critical periods of gradual oxygen deficit as shown by the maintenance of renal blood flow during severe systemic hypoxia, and by improved cerebrovascular autoregulation in hemorrhagic hypotension. On the other hand, aIUGR leads to the reduction of the number of nephrons and to impaired renal excretory functions with arterial hypertension and chronic renal failure.

Animals↗
PubMed2003

Lung perfusion, shunt fraction, and oxygenation during one-lung ventilation in pigs: the effects of desflurane, isoflurane, and propofol.

OBJECTIVE: To study how desflurane, isoflurane, and propofol affect pulmonary perfusion, shunt fraction, and systemic oxygenation during one-lung ventilation (OLV) in vivo. DESIGN: Prospective animal study with a crossover design. SETTING: Animal laboratory of a university hospital. PARTICIPANTS: Twelve female pigs. INTERVENTIONS: The pigs were anesthetized, tracheally intubated, and mechanically ventilated. After placement of femoral arterial and thermodilution pulmonary artery catheters, a left-sided, double-lumen tube (DLT) was placed via tracheotomy. After DLT placement, F(I)O(2) was adjusted at 0.8, and anesthesia was continued in random order with 1 minimal alveolar concentration of desflurane, 1 minimal alveolar concentration of isoflurane, or propofol. MEASUREMENTS AND MAIN RESULTS: Measurements of respiratory and hemodynamic parameters were made after stabilization at each anesthetic. During OLV, perfusion of the nonventilated lung and shunt fraction were comparable during all 3 anesthetics. PaO(2) was lower during desflurane and isoflurane anesthesia as compared with propofol anesthesia. Mixed venous PO(2) and cardiac output were lower with desflurane and isoflurane as compared with propofol. CONCLUSIONS: In a clinically relevant model of OLV cardiac output, PaO(2) and mixed venous PO(2) decreased during desflurane and isoflurane as compared with propofol, whereas perfusion of the nonventilated lung and shunt fraction remained comparable.

Anesthetics, Inhalation↗
PubMed2003

Effect of estradiol sulfamate (ES-J995) on affinity of hemoglobin for oxygen, cardiovascular function and acid-base balance in ovariectomized rats.

Oral administration of estradiol sulfamate (ES, prodrug of estradiol) leads to increased systemic and reduced hepatic effects than estradiol because ES is accumulated in erythrocytes. However, possible alterations of erythrocytic oxygen transport by intraerythrocytic ES accumulation has not been studied. Therefore, ovariectomized adult female rats (n = 58; body wt.) were randomly treated orally either with single doses (day 1) or multiple dose (days 1-4) with vehicle, with estradiol sulfamate (ES-J995, 1 mg x kg(-1) b.w.) or with estradiol (30 mg x kg(-1) b.w.). Under general anesthesia arterial blood pressure, heart rate, blood gases, and acid-base balance were measured. Hypoxia was performed by lowering the inspired fraction of oxygen from 0.35 to 0.12. In addition, individual oxygen dissociation curves and ES-J995 distribution in blood and plasma were estimated. ES-J995 was accumulated in erythrocytes by approximately 98% (P < 0.01), but oxygen transport capacity was not altered (P50: 35.6 +/- 1.0 mm Hg to 37.1 +/- 1.1 mm Hg). Blood gases and acid-base balance parameters were not altered after ES-J995 treatment under normoxic and hypoxic conditions. In conclusion, ES-J995 accumulation in erythrocytes does not alter the affinity of hemoglobin for oxygen nor any function which would indicate an impaired oxygen delivery to the body.

Acid-Base Imbalance↗
PubMed2002

The Drosophila gap junction channel gene innexin 2 controls foregut development in response to Wingless signalling.

In invertebrates, the direct communication of neighbouring cells is mediated by gap junctions, which are composed of oligomers of the innexin family of transmembrane proteins. Studies of the few known innexin mutants in Drosophila and C. elegans have shown that innexin proteins, which are structurally analogous to the connexins in vertebrates, play a major structural role as gap junctional core components in electric signal transmission. We show that Drosophila innexin 2 mutants display a feeding defect that originates from a failure of epithelial cells to migrate and invaginate during proventriculus organogenesis. The proventriculus is a valve-like organ that regulates food passage from the foregut into the midgut. Immunohistological studies indicate that innexin 2 is functionally required to establish a primordial structure of the proventriculus, the keyhole, during the regionalisation of the embryonic foregut tube, which is under the control of Wingless and Hedgehog signalling. Our genetic lack- and gain-of-function studies, and experiments in Dorsophila tissue culture cells provide strong evidence that innexin 2 is a target gene of Wingless signalling in the proventricular cells. This is the first evidence, to our knowledge, that an invertebrate gap junction gene controls epithelial tissue and organ morphogenesis in response to the conserved WNT signalling cascade.

Animals↗
PubMed2002

Effect of hypoxia/hypercapnia on metabolism of 6-[(18)F]fluoro-L-DOPA in newborn piglets.

There is evidence that the dopaminergic system is sensitive to altered p(O(2)) in the immature brain. However, the respective enzyme activities have not been measured in the living neonatal brain together with brain oxidative metabolism. Therefore 18F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with positron emission tomography (PET) was used to estimate the activity of the aromatic amino acid decarboxylase (AADC) in the brain of fifteen newborn piglets (2-5 days old). Two PET scans were performed in each piglet. Eleven animals underwent a period of normoxia and moderate hypoxia/hypercapnia (H/H). The remaining four animals were used as an untreated control group. Simultaneously, the brain tissue p(O(2)) was recorded, the regional cerebral blood flow (CBF) was measured with colored microspheres and the cerebral metabolic rate of oxygen (CMRO(2)) was determined. In addition, in four untreated and six H/H treated piglets the relative amounts of fluorodopamine and the respective metabolites were determined in brain tissue samples using HPLC analysis. H/H conditions were induced by lowering the inspired fraction of oxygen from 0.35 to 0.10 and adding CO(2) to the inspired gas resulting in an arterial p(CO(2)) between 74 and 79 mmHg. H/H elicited a more than 3-fold increase of the CBF (P<0.05) so that the CMRO(2) remained unchanged throughout the H/H period. Despite this, the brain tissue p(O(2)) was reduced from 19+/-4 to 6+/-3 mmHg (P<0.05). The permeability-surface area product of FDOPA (PS(FDOPA)) was unchanged. However, the transfer rate of FDOPA (k(3)(FDOPA)) of the nigrostriatal dopaminergic system and the relative amounts of fluorodopamine and the respective metabolites were significantly increased (P<0.05). It is suggested that H/H induces an increase of AADC activity. However, an H/H-induced CBF increase maintains bulk O(2) delivery and preserves CMRO(2).

Animals↗
PubMed2002

Developmental changes in cerebral autoregulatory capacity in the fetal sheep parietal cortex.

We validated laser Doppler flowmetry (LDF) for long-term monitoring and detection of acute changes of local cerebral blood flow (lCBF) in chronically instrumented fetal sheep. Using LDF, we estimated developmental changes of cerebral autoregulation. Single fibre laser probes (0.4 mm in diameter) were implanted in and surface probes were placed on the parietal cerebral cortex at 105 +/- 2 (n = 7) and 120 +/- 2 days gestational age (dGA, n = 7). Basal lCBF was monitored over 5 days followed by a hypercapnic challenge (fetal arterial partial pressure of CO(2), P(a,CO2): 83 +/- 3 mmHg) during which lCBF changes obtained by LDF were compared to those obtained with coloured microspheres (CMSs). Mean arterial blood pressure (MABP) was increased and decreased using phenylephrine and sodium nitroprusside at 110 +/- 2 and 128 +/- 2 dGA. Intracortical and cortical surface laser probes gave stable measurements over 5 days. The lCBF increase during hypercapnia obtained by LDF correlated well with flows obtained using CMS (r = 0.89, P < 0.01). The signals of intracortical and surface laser probes also correlated well (r = 0.91, P < 0.01). Gliosis of 0.35 +/- 0.06 mm around the tip of intracortical probes did not affect the measurements. The range of MABP over which cerebral autoregulation was observed increased from 20-48 mmHg at 110 dGA to 35 to > 95 mmHg at 128 dGA (P < 0.05). Since MABP increased from 33 to 54 mmHg over this period (P < 0.01), the range between the lower limit of cerebral autoregulation and the MABP increased from 13 mmHg at 110 dGA to 19 mmHg at 128 dGA (P < 0.01). LDF is a reliable tool to assess dynamic changes in cerebral perfusion continuously in fetal sheep.

Animals↗
PubMed2001

Campylobacter upsaliensis exerts a cytolethal distending toxin effect on HeLa cells and T lymphocytes.

Campylobacter upsaliensis is an emerging human enteropathogen. However, little is known about the pathogenesis of C. upsaliensis infection. In this study the authors demonstrate that C. upsaliensis whole-cell preparations and extracts produce a cytolethal distending toxin (CDT)-like effect on HeLa cells characterized by progressive distension and nuclear fragmentation culminating in cell death over 5 d. To further delineate the nature of this toxic effect in relation to CDT from other pathogens, the effect of C. upsaliensis on cellular events in epithelial cells and immunocytes was investigated. C. upsaliensis lysate-treated HeLa cells subjected to FACScan analysis using carboxyfluorescein diacetete succinimidyl ester (CFDA-SE) as a cell tracer demonstrated cell division arrest. Propidium iodide (PI) staining of HeLa cells revealed that cell cycle arrest occurred in G(2)/M. Human T lymphocytes exposed to C. upsaliensis lysates also showed cell cycle arrest in G(2)/M. Using a combination of Annexin V/PI staining and TUNEL assay, cytodistended HeLa cells were shown to undergo apoptotic cell death. These data provide the first insights into the virulence mechanisms of this novel enteropathogen.

Bacterial Toxins↗
PubMedDate not supplied

Cellular distribution of innexin 1 and 2 gap junctional channel proteins in epithelia of the Drosophila embryo.

Invertebrate gap junctions are composed of Innexin channel proteins that are structurally and functionally analogous to the connexins in vertebrates. In situ hybridization experiments have shown that most of the eight known innexin genes in Drosophila are expressed in a complex and overlapping temporal and spatial profile, with several members showing high levels of expression in developing epithelia of the embryo. To further study the cellular roles of Innexins, we have generated antibodies against Innexins 1 and 2 and studied their protein distribution in the developing embryo. We find that both Innexins are co-expressed in a number of epithelial tissues including the epidermis, the gut and the salivary glands. On the cellular level, we find both proteins localized to the membranes of epithelial cells. Immunohistochemical analysis using cell polarity markers indicates that Innexin 1 is predominantly localized to the baso-lateral domain of epithelial cells, basal to septate junctions. In contrast, we find a variable positioning of Innexin 2 along the apico-basal axis of epithelial cells depending on the type of tissue and organ. Our findings suggest that the distribution of Innexin channel proteins to specific membrane domains of epithelial cells is regulated by tissue specific factors during the development of epithelia in the fly embryo.

Animals↗