Grouping of animals, induction of trauma and outcome analysis were performed by different researchers. In the contralateral cortex exhibiting less pronounced cerebral damage, a spontaneous improvement of CCT was observed within this time frame that was not affected by HBOT.
Mehr Strategie und Ergebnisorientiertheit und bekräftigt die einzigartige und ständig wachsende Bedeutung der Beziehungen zwischen der Europäischen Union und den Vereinigten Staaten. Focusing on Strategy and Delivering Results, restates the unique and ever-increasing importance of the relationship between the European Union and the United States.
Effectiveness also calls for more result-oriented guidelines, leading to less emphasis on methods used, and better definition of results to be achieved. Der belgische Föderale Öffentliche Dienst Soziale Sicherheit hat ein dynamisches Arbeitsumfeld geschaffen, in dem neue Arbeitsformen erprobt werden, um Methoden wie flexible Bürokonstellationen Desk-Sharing , Teleheimarbeit, verstärkte Ergebnisorientiertheit und flexible Arten von Teamstrukturen und Teamarbeit zu fördern.
The Belgian FPS Social Security has created a dynamic workplace where new ways of working have been implemented to promote practices such as desk sharing, home working, increased focus on results and more flexible ways in which teams are structured and work. In der Betonung des Prozesshaften bestand der wesentliche Unterschied zur Ergebnisorientiertheit vergleichbarer konstruktiver Ansätze seiner Minimalistenkollegen Donald Judd oder Carl Andre.
LeWitt postulierte eine klare Aufgabenstellung, eine experimentelle, quasi wissenschaftliche Versuchsanordnung, die mit methodischem Ansatz streng ausgeführt ein Resultat hervorbringen könne, das für den Künstler ebenso überraschend sei wie für den Betrachter.
His emphasis on process formulated the essential difference to the similarly constructive approaches of his Minimalist colleagues Donald Judd or Carl Andre, who were more result-oriented.
LeWitt postulated a clear task, an experimental, quasi-scientific investigation whose methodical approach, when executed precisely, could bring about a result that was as surprising to the artist as it was to the viewer.
Future cooperation will consider innovative forms of implementation, as set out in the Agenda for Change, the EU's blueprint to make development aid more efficient and more result-targeted. Bei der Ausarbeitung der Strategiepapiere gelten folgende Grundsätze der Wirksamkeit der Entwicklungszusammenarbeit: The preparation of strategy papers shall apply principles of aid effectiveness: The preparation and implementation of the PDSD shall apply principles of aid effectiveness: The preparation and implementation of strategy papers shall comply with the principles of aid effectiveness: More context All My memories Ask Google.
German Wir erwarten von unseren Partnern, dass sie die gleiche Ergebnisorientiertheit und Offenheit an den Tag legen. English We look to our partners to express the same sense of purpose and openness. English The key aim of the report is the simplification and clarification of practices and administration, and increased results. English The advantage of this type of administration is that it is results-oriented and may, under the right conditions, make for effective Structural Fund assistance.
German Die Europäische Kommission hat heute eine Mitteilung an den Rat und das Europäische Parlament über die Stärkung der transatlantischen Beziehungen durch mehr Strategie und Ergebnisorientiertheit angenommen.
English The European Commission has adopted today a Communication to the Council and the European Parliament on reinforcing the transatlantic relationship, through focusing on strategy and delivering results.
German Diese Grundsätze sind: English These principles are: Patient heterogeneity as well as differences in study design and treatment modalities make the direct comparison of these results difficult. Although experimental studies are also based on varying animal models of brain injury and different HBO treatment modalities, the standardized set up of these studies allows for a more detailed exploration of the protective or detrimental effects of HBOT.
HBO treatment following experimental brain trauma was demonstrated to support recovery of aerobic metabolic function  , an increase in overall cerebral glucose metabolism and cerebral PO 2  ,  , an increase in vascular density and spatial learning  , a significant reduction of apoptosis, higher cell counts as well as a denser axonal network  , .
Thus far, experimental observations have primarily been based on short-term studies during the acute phase of injury. Generally, HBO treatment was started within 3 hours of brain injury and pursued for a maximum of five days with the number of HBOT treatments varying between 1 and 6 sessions  —  ,  ,  ,  — . At the same time, however, neurological improvements following TBI in the clinical setting have often been reported following 20 to HBOT sessions  ,  — .
We therefore hypothesized that repetitive long-term HBO treatment following traumatic brain injury would have more pronounced effects and might modulate different cerebral functions than short-term treatment during the acute phase of TBI only. To test this hypothesis, we analysed the effects of repetitive HBOT treatment applied over a 3-week period following moderate and severe lateral fluid percussion head injuries. The HBOT-mediated modulation of sensorimotor functions and of somatosensory-evoked potentials was evaluated every week.
Due to a pronounced decrease in the central conduction time in the ipsilateral hemispheres following four weeks of HBOT treatments, the myelination of neurons in the injured hemispheres was investigated in more detail. Our results indicate that long-term HBO treatment following brain injury mediates pronounced remyelination in the ipsilateral cortex, which in turn, is associated with a significant increase in motor function improvement.
Each treatment lasted 1 hour. The procedure was repeated on days 2 and 3 after injury induction and at weeks 1, 2 and 3 for a further 3 days each Fig. Morphological changes, somatosensory-evoked potentials SSEP , protein expression and behavioural tests were analysed following the three successive HBO treatments at days 4, 10, 16 and Correlation between trauma severity and outcome were assessed for different parameters.
Trauma severity-associated changes were only observed for the analysis of neurological motor function by the Rotarod performance test and the composite neuroscore testing paradigm for correlation analysis see Fig.
S1 , S2 and S4. Traumatic brain injury results in progressive long-term functional and structural brain damage due to elevated inflammation, suppressed regeneration and cell death. This is in accordance with our previous results documenting pronounced ipsilateral cerebral damage within 3 weeks following traumatic brain injury . HBOT-associated reduction in these lesions was also observable at this time point.
Due to the variability in the trauma-induced lesions, quantitative analysis of the structural damage was not possible. In Table S1 the number of animals with or without distinct lesions in the different groups is summarized. The lesions observed in the ispilateral cortex of HBO-treated animals appear less pronounced. Trauma-associated extensive ipsilateral cortical damage might be accompanied by the impaired integrity of the central neuronal pathways.
Amplitude-latency analysis was used to assess somatosensory-evoked potentials SSEP. After collecting complete SSEP data, the stored recordings were evaluated for the presence of the main cervical potential in the channel Cerv-Fpz and the primary cortical potentials in the channels of C3'-Fpz and C4'-Fpz Fig. Schematic representation of the somatosensory-evoked potential recording sites adapted from the human 10—20 system. The central conduction time CCT is calculated by subtracting the peak latency of the major response from the neck from the latency of the primary cortical response C.
Time-dependent modulation in the central conduction time recorded at the ipsi- and contralateral hemisphere in treated and untreated brain injured rats.
HBO-treated brain injured rats; open circle: The mean CCT of sham animals as well as brain-injured animals before induction of trauma baseline was recorded at 4. CCT values obtained from the ipsilateral side C4'-Fpz increased in treated and untreated animals within 4 days post-trauma Fig.
Two weeks post-trauma, the mean conduction time was delayed by 2. At three weeks post-trauma CCT values worsened significantly in brain-injured animals.
A similar time-dependent pattern of CCT modulations was observed in the contralateral hemisphere at the early time points of observation. However, a spontaneous recovery of the central conduction times was observed in the contralateral hemisphere that was comparable to the HBO treatment-induced changes in the ipsilateral hemisphere Fig. Myelin basic proteins MBP are essential constituents of the myelin sheath. There are several size isoforms of MBP formed by differential splicing of seven exons.
In rats, MBP constitute the We observed an injury-associated time-dependent biphasic reduction in the expression of MBP isoforms The only statistically significant trauma-induced decrease of MBP expression as compared to sham controls was detected for isoform A distinct pattern of MBP isoform kDa expression was not established.
Statistically expression analysis of this isoform has thereby been omitted. Upregulation of isoform However, upregulation of isoform A-D Myelin basic protein isoform expression at days 4, 11, 16 and 22 as percentage of expression in sham controls and representative western blot gels.
The distinct HBOT-associated increase in MBP isoform expression 22 days post-injury was accompanied by a remyelination in the ipsilateral cortex. Statistically significant augmentation of myelin sheet in the ipsilateral cortex following three weeks of HBO treatment of the severely injured group was demonstrated by an increase in Luxol Fast Blue staining Fig.
Furthermore, proteolipid protein PLP , a predominant myelin protein in the central nervous system, that was down-regulated in the ipsilateral cortex following trauma, was detectable again after 22 days of HBO treatment by immunohistochemistry Fig. Quantitative analysis of myelin stained by Luxol Fast Blue. The ipsilateral hemisphere was analysed as a whole in order to avoid bias. Exemplification of proteolipid protein PLP staining at day 22 following induction of traumatic brain injury and HBO treatment; number of animals see Table 1.
Lateral fluid percussion injury resulted in pronounced cerebral damage of the ipsilateral sensorimotor cortex that was associated with a significant decrease in the amplitude latency as assessed by SEP. We therefore evaluated the motor abilities of the animals following injury and repetitive long-term HBO treatment.
Sensorimotor function was evaluated by the Rotarod test that demands complex movement and coordination abilities and the composite neuroscore that consisted of forelimb reflex, hindlimb flexion, lateral pulsion, and angle board tests . Due to individual differences in baseline performance results obtained for each animal before traumatic brain injury post-injury performance on the Rotarod was analysed as percentage of the baseline values.
An injury—induced, time-dependent decrease in the maximal speed maintained by the animals was observed in moderately and severely injured rats Fig. Note that uneven group sizes arise from missing data points in some animals, which were excluded in repeated measures mixed model ANOVA. It should be taken into account that Rotarod performance is training dependent.
Accordingly, the injury-induced sensorimotor impairment was statistically significant at each time point in severely injured animals as compared to the performance of sham animals at the different time points Fig. Sensorimotor function impairment was compensated by HBO treatment. Among severely injured animals, the HBO-treated group showed a significantly better performance overall Fig.
The most pronounced HBOT-mediated compensation was observed after three weeks of repetitive treatment independent of injury severity Fig. At this time point the performance of treated animals was comparable to the performance of the trained uninjured sham controls Fig. Composite neuroscores were not significantly affected following induction of moderate trauma.
Accordingly the effect of HBO treatment in this group was inconsequential Fig. Hyperbaric oxygen treatment in a clinical setting is usually implemented in the form of repetitive sessions over extensive time periods in order to improve neurological outcomes following traumatic brain injury .
The results presented here demonstrate for the first time some of the potential mechanisms underlying the protective effect of repetitive long-term HBO treatment in an experimental traumatic brain injury model.
Our analysis was focused on cerebral tissue modulations and associated functional improvements that are potentially related to the significant improvement of somatosensory-evoked potentials observed after three weeks of treatment. SSEPs have been widely used at intensive care units since the late s to supplement clinical, radiological and other parameters in assessing neurological function and outcome of patients suffering severe traumatic brain injuries  — .
The central conduction time CCT proved to be an important parameter of SSEP in assessing the neurological function of the brain following traumatic brain injury, because it strongly correlates with the impact of the initial trauma and proved to predict neurological outcome  , .
A delay in CCT observed during trauma or in demyelinating diseases has been linked to conduction changes of the subcortical fiber tracts . Vice versa, CCT decrease can be measured as a result of the remyelination of subcortical fiber tracts  ,  — . Modulation of CCT following cerebral injury or therapeutic interventions might thereby be closely linked to demyelination or remyelination processes, respectively.
Extensive traumatic brain injury-associated white matter demyelination has been reported using animal models  ,  and in human studies . In our experimental setting, a significant decrease in CCT was observed in the ipsilateral cortex of brain injured rats at late stages of disease progression after three weeks of repetitive HBO treatment. The significance of treatment duration for improvement of neurophysiological function is underlined by a study that reported the protective effects of short-term HBO treatment on cerebral integrity but no recovery of evoked potentials in brain injured rabbits following short-term treatment .
In the contralateral cortex exhibiting less pronounced cerebral damage, a spontaneous improvement of CCT was observed within this time frame that was not affected by HBOT. The spontaneous improvement of the CCT in the contralateral hemisphere is in accordance with observations that report inflammation-induced default remyelination in the central nervous system  — . The time-dependent modulation in myelin basic protein expression observed in the ipsilateral cortex by western blot analysis indicates the HBOT-mediated improvement of CCT to be potentially due to remyelination processes.
The exon II containing The isoform is also expressed in highly differentiated oligodendrocytes. It has been associated with protective processes such as inhibition of apoptosis and myelin turnover .
The impact of HBO seemed to be biphasic with rapid but less pronounced changes in MBP isoform expression after 4 days and significant modulations after two and three weeks of treatment. It should be noted that despite a progressive delay of CCT in week 1 and 2 following trauma, a noteworthy decrease in the expression of the MBP isoforms was not detected at these time points.
This is in accordance with studies that have only observed a down-regulation of the phosphorylated isoform Furthermore in early multiple sclerosis studies up-regulation of isoform Up-regulation of MBP isoform expression was accompanied by an increase in Luxol Fast Blue staining in the ipsilateral cortex. These observations underline the notion of an HBO-associated recovery of fibre tracts by remyelination as indicated by the decrease of CCTs following three weeks of treatment.
HBO treatment-associated neurophysiological recovery was accompanied by a pronounced and statistically significant improvement in neuronal function of brain injured rats. A pronounced and statistically significant recovery in neuronal function has been reported in a variety of studies implementing HBO treatment following brain injury. In most of these studies neurological function was shown to significantly improve within hours of early treatment often after one treatment session  — .
Although there was a distinct tendency of behavioural advancement at 4 days following three consecutive HBOT sessions in our study, a statistically significant improvement in sensory motor function of severely injured animals as compared to untreated animals was observed at the earliest after 10 days and six consecutive HBO sessions. However it should be noted that the maximum speed the injured HBO treated animals were able to control on the Rotarod was comparable or beyond the speed maintained before injury, indicating an enhancing effect of HBO treatment on the training abilities of the animals.
An improvement of neurological function exceeding the abilities of the animals before injury has not been shown in any of the other studies analysing the protective effect of HBO treatment following brain injury.
It has to be taken into account though that a direct comparison of the results is problematic, since injury models, HBO treatment modalities and behavioural and comparative group analysis varies considerably in different studies. The deacon Jamie Beamish. The chancellor of the exchequer John Atterbury. Sheriff's assistant Luke Evans. Gaffer Tom Roy Holder. Baron Baldwin's young son Mark David. Margaret Walter's servant Ruby Bentall. The sentry Ned Dennehy. The French cook Nicolas Simon.
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