| 1. |
- Bentzer, Peter, et al.
(författare)
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Infusion of prostacyclin following experimental brain injury in the rat reduces cortical lesion volume
- 2001
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 18:3, s. 275-285
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial-derived prostacyclin is an important regulator of microvascular function, and its main actions are inhibition of platelet/leukocyte aggregation and adhesion, and vasodilation. Disturbances in endothelial integrity following traumatic brain injury (TBI) may result in insufficient prostacyclin production and participate in the pathophysiological sequelae of brain injury. The objective of this study was to evaluate the potential therapeutic effects of a low-dose prostacyclin infusion on cortical lesion volume, CA3 neuron survival and functional outcome following TBI in the rat. Anesthetized animals (sodium pentobarbital, 60 mg/kg, i.p.) were subjected to a lateral fluid percussion brain injury (2.5 atm) or sham injury. Following TBI, animals were randomized to receive a constant infusion of either prostacyclin (1 ng/kg x min(-1) i.v.) or vehicle over 48 h. All sham animals received vehicle (n = 6). Evaluation of neuromotor function, lesion volume, and CA3 neuronal loss was performed blindly. By 7 days postinjury, cortical lesion volume was significantly reduced by 43% in the prostacyclin-treated group as compared to the vehicle treated group (p < 0.01; n = 12 prostacyclin, n = 12 vehicle). No differences were observed in neuromotor function (48 h and 7 days following TBI), or in hippocampal cell loss (7 days following TBI) between the prostacyclin- and vehicle-treated groups. We conclude that prostacyclin in a low dose reduces loss of neocortical neurons following TBI and may be a potential clinical therapeutic agent to reduce neuronal cell death associated with brain trauma.
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| 2. |
- Deierborg Olsson, Tomas, et al.
(författare)
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Overexpression of UCP2 protects thalamic neurons following global ischemia in the mouse.
- 2008
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 28, s. 1186-1195
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Tidskriftsartikel (refereegranskat)abstract
- Uncoupling protein 2 (UCP2) is upregulated in the brain after sublethal ischemia, and overexpression of UCP2 is neuroprotective in several models of neurodegenerative disease. We investigated if increased levels of UCP2 diminished neuronal damage after global brain ischemia by subjecting mice overexpressing UCP2 (UCP2/3tg) and wild-type littermates (wt) to a 12-min global ischemia. The histopathological outcome in the cortex, hippocampus, striatum, and thalamus was evaluated at 4 days of recovery, allowing maturation of the selective neuronal death. Global ischemia led to extensive cell death in the striatum, thalamus, and in the CA1 and CA2, and less-pronounced cell death in the CA3 and dentate gyrus (DG) hippocampal subfields. Histologic damage was significantly lower in the ventral posterolateral VPL and medial VPM thalamic nuclei in UCP2/3tg animals compared with wt. These thalamic regions showed a larger increase in UCP2 expression in UCP2/3tg compared with wt animals relative to the nonprotected DG. In the other regions studied, the histologic damage was lower or equal in UCP2/3tg animals compared with wt. Consequently, neuroprotection in the thalamus correlated with a high expression of UCP2, which is neuroprotective in a number of models of neurodegenerative diseases.Journal of Cerebral Blood Flow & Metabolism advance online publication, 27 February 2008; doi:10.1038/jcbfm.2008.8.
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| 3. |
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| 4. |
- Hansson, Magnus, et al.
(författare)
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Increased potassium conductance of brain mitochondria induces resistance to permeability transition by enhancing matrix volume.
- 2010
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 285, s. 741-750
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Tidskriftsartikel (refereegranskat)abstract
- Modulation of K+ conductance of the inner mitochondrial membrane has been proposed to mediate preconditioning in ischemia-reperfusion injury. The mechanism is not entirely understood but it has been linked to a decreased activation of mitochondrial permeability transition (mPT). In the present study, K+ channel activity was mimicked by picomolar concentrations of valinomycin. Isolated brain mitochondria were exposed to continuous infusions of calcium. Monitoring of extramitochondrial Ca2+ and mitochondrial respiration provided a quantitative assay for mPT-sensitivity by determining calcium retention capacity (CRC). Valinomycin and cyclophilin D-inhibition separately and additively increased CRC. Comparable degrees of respiratory uncoupling induced by increased K+ or H+ conductance had opposite effects on mPT sensitivity. Protonophores dose-dependently decreased CRC, demonstrating that so-called mild uncoupling was not beneficial per se. The putative mitoKATP channel opener diazoxide did not mimic the effect of valinomycin. An alkaline matrix pH was required in order for mitochondria to retain calcium, but increased K+ conductance did not result in augmented DeltapH. The beneficial effect of valinomycin on CRC was not mediated by H2O2-induced PKCepsilon activation. In contrast, increased K+ conductance reduced H2O2 generation during calcium infusion. Lowering the osmolarity of the buffer induced an increase in mitochondrial volume and improved CRC similar to valinomycin without inducing uncoupling or otherwise affecting respiration. We propose that increased potassium conductance in brain mitochondria may cause a direct physiological effect on matrix volume inducing resistance to pathological calcium challenges.
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| 5. |
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| 6. |
- Jungner, Mårten, et al.
(författare)
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Effects on brain edema of crystalloid and albumin fluid resuscitation after brain trauma and hemorrhage in the rat.
- 2010
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Ingår i: Anesthesiology. - 1528-1175. ; 112:5, s. 1194-1203
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It has been hypothesized that resuscitation with crystalloids after brain trauma increases brain edema compared with colloids, but previous studies on the subject have been inconclusive. To test this hypothesis, the authors compared groups resuscitated with either colloid or crystalloid. METHODS: After fluid percussion injury, rats were subjected to a controlled hemorrhage of 20 ml/kg and were randomized to 5% albumin at 20 ml/kg (A20), isotonic Ringer's acetate at 50 ml/kg (C50), or 90 ml/kg (C90). After 3 or 24 h, water content in the injured cortex was determined using a wet/dry weight method. Blood volume was calculated from plasma volume, measured by 125I-albumin dilution, and hematocrit. Oncotic pressure and osmolality were measured with osmometers. RESULTS: At 3 h, blood volume was equal in the A20 and C90 groups and lower in the C50 group. Oncotic pressure was reduced by 35-40% in the crystalloid groups and unchanged in the albumin group. Cortical water content in the A20 group was lower than in the C90 group (81.3 +/- 0.5% vs. 82.1 +/- 1.1%, P < 0.05), but it was not different from the C50 group (81.8 +/- 1.1%). At 24 h, oncotic pressure and blood volume were normalized in all groups, and cortical water content was significantly lower in the albumin group than in the crystalloid groups. Osmolality and arterial pressure were equal in all groups throughout the experiment. CONCLUSIONS: When given to the same intravascular volume expansion, isotonic crystalloids caused greater posttraumatic brain edema than 5% albumin at 3 and 24 h after trauma.
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| 7. |
- Lybeck, Anna, et al.
(författare)
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Bedside interpretation of simplified continuous EEG after cardiac arrest
- 2020
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 64:1, s. 85-92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Continuous EEG-monitoring (cEEG) in the ICU is recommended to assess prognosis and detect seizures after cardiac arrest but implementation is often limited by the lack of EEG-technicians and experts. The aim of the study was to assess ICU physicians ability to perform preliminary interpretations of a simplified cEEG in the post cardiac arrest setting. Methods: Five ICU physicians received training in interpretation of simplified cEEG - total training duration 1 day. The ICU physicians then interpreted 71 simplified cEEG recordings from 37 comatose survivors of cardiac arrest. The cEEG included amplitude-integrated EEG trends and two channels with original EEG-signals. Basic EEG background patterns and presence of epileptiform discharges or seizure activity were assessed on 5-grade rank-ordered scales based on standardized EEG terminology. An EEG-expert was used as reference. Results: There was substantial agreement (κ 0.69) for EEG background patterns and moderate agreement (κ 0.43) for epileptiform discharges between ICU physicians and the EEG-expert. Sensitivity for detecting seizure activity by ICU physicians was limited (50%), but with high specificity (87%). Conclusions: After cardiac arrest, preliminary bedside interpretations of simplified cEEGs by trained ICU physicians may allow earlier detection of clinically relevant cEEG changes, prompting changes in patient management as well as additional evaluation by an EEG-expert. This strategy requires awareness of limitations of both the simplified electrode montage and the cEEG interpretations performed by ICU physicians. cEEG evaluation by an expert should not be delayed.
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| 8. |
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| 9. |
- Mattiasson, Gustav
(författare)
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Experimental Traumatic Brain Injury and Cell Death - in vivo and in vitro aspects
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic and ischemic brain damage are major causes of disability and death. While much effort has been spent on developing pharmacological treatments for these conditions, no neuroprotective drugs are in clinical use. Neuronal death following trauma and ischemia occurs in selected cell populations of the brain at various time points after the injury, and causes cognitive and behavioral dysfunction. The injury mechanisms are similar in both types of injury. Brain trauma causes ischemia, and mitochondrial dysfunction is an important initiator of both types of cell death. In the first part of the study, a clinically relevant model of traumatic brain injury (TBI) in the rat was used to evaluate the rotating pole test as a test of neuromotor function, as well as the neuroprotective effect of administration of a low dose of prostacyclin following TBI. The rotating pole test was useful to assess outcome and functional improvement following injury, and administration of prostacyclin led to a significantly reduced cortical lesion volume, presumably through an improved microcirculation. Here we show that a low dose of prostacyclin without side effects such as systemic hypotension reduces cell death following experimental TBI. In the second part of the study, the role of mitochondria in cell death following acute brain injury was studied. A flow cytometric method for the analysis of minute samples of isolated brain mitochondria was developed, and applied to compare mitochondria from hippocampal subregions. Cell vulnerability correlated with an increased mitochondrial production of reactive oxygen species and increased sensitivity to calcium-induced mitochondrial permeability transition (mPT). In the final study, we used a functional genomics approach to identify potentially neuroprotective genes that were upregulated following ischemic preconditioning. Increased expression of the mitochondrial protein UCP-2 correlated with cell survival, and overexpression of UCP-2 was neuroprotective both in vivo and in vitro. The results suggest that under basal conditions, UCP-2 may signal through cellular redox systems to upregulate neuroprotective genes. Following injury, UCP-2 inhibits mPT, activation of caspases and cell death. Mitochondrial involvement in ischemic and traumatic brain injury is supported by the strong neuroprotective effect of inhibitors of mPT (e.g. cyclosporin A). The uncoupling proteins have attracted much interest as potential targets for the treatment of obesity, which have led to devlopment of pharmacological inducers of these proteins. The results of this study suggest that such compounds may also be used to induce neuroprotection.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Mattiasson, Gustav, et al.
(författare)
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The rotating pole test: evaluation of its effectiveness in assessing functional motor deficits following experimental head injury in the rat
- 2000
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Ingår i: Journal of Neuroscience Methods. - 1872-678X. ; 95:1, s. 75-82
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Tidskriftsartikel (refereegranskat)abstract
- Neurological motor dysfunction is often an integral component of the neurological sequelae of traumatic brain injury (TBI). In experimental TBI, neurological motor testing is an outcome measure used to monitor severity of injury, and the response to treatment. This study evaluates the effectiveness and sensitivity of the rotating pole test (RP) to characterize and evaluate the temporal course of motor deficits after lateral fluid percussion (FP) injury to the rat brain. The results are compared with the previously characterized and widely used composite neuroscore of motor function (NS). The animals were required to walk across an elevated wooden pole that was either stationary or rotating to left or right directions at different speeds. Male Wistar rats underwent lateral FP injury of moderate severity (mean 2.4 atm, n = 9) or sham surgery (n = 9), and were tested at 48 h and 7 days post-injury using the NS and RP. The results of the NS directly correlated to the results of the RP, showing a significant injury effect at both 48 h and 7 days. This is the first study to show that the RP-test detects neurological motor deficits after lateral FP injury, and suggests that this technique is a reliable behavioral tool for evaluating neurological motor function in the acute period after experimental TBI.
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| 14. |
- Mattiasson, Gustav, et al.
(författare)
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Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma.
- 2003
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 9:8, s. 1062-1068
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Tidskriftsartikel (refereegranskat)abstract
- Whereas uncoupling protein 1 (UCP-1) is clearly involved in thermogenesis, the role of UCP-2 is less clear. Using hybridization, cloning techniques and cDNA array analysis to identify inducible neuroprotective genes, we found that neuronal survival correlates with increased expression of Ucp2. In mice overexpressing human UCP-2, brain damage was diminished after experimental stroke and traumatic brain injury, and neurological recovery was enhanced. In cultured cortical neurons, UCP-2 reduced cell death and inhibited caspase-3 activation induced by oxygen and glucose deprivation. Mild mitochondrial uncoupling by 2,4-dinitrophenol (DNP) reduced neuronal death, and UCP-2 activity was enhanced by palmitic acid in isolated mitochondria. Also in isolated mitochondria, UCP-2 shifted the release of reactive oxygen species from the mitochondrial matrix to the extramitochondrial space. We propose that UCP-2 is an inducible protein that is neuroprotective by activating cellular redox signaling or by inducing mild mitochondrial uncoupling that prevents the release of apoptogenic proteins.
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| 15. |
- Philips, Matthew F., et al.
(författare)
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Neuroprotective and behavioral efficacy of nerve growth factor-transfected hippocampal progenitor cell transplants after experimental traumatic brain injury
- 2001
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Ingår i: Journal of Neurosurgery. - 0022-3085. ; 94:5, s. 765-765
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Tidskriftsartikel (refereegranskat)abstract
- OBJECT: Immortalized neural progenitor cells derived from embryonic rat hippocampus (HiB5), were transduced ex vivo with the gene for mouse nerve growth factor (NGF) to secrete NGF (NGF-HiB5) at 2 ng/hr/10(5) cells in culture. METHODS: Fifty-nine male Wistar rats weighing 300 to 370 g each were anesthetized with 60 mg/kg sodium pentobarbital and subjected to lateral fluid-percussion brain injury of moderate severity (2.3-2.4 atm, 34 rats) or sham injury (25 rats). At 24 hours postinjury, 2 microl (150,000 cells/microl) of [3H]thymidine-labeled NGF-HiB5 cells were transplanted stereotactically into three individual sites in the cerebral cortex adjacent to the injury site (14 rats). Separate groups of brain-injured rats received nontransfected (naive [n])-HiB5 cells (12 animals) or cell suspension vehicle (eight animals). One week postinjury, animals underwent neurological evaluation for motor function and cognition (Morris water maze) and were killed for histological, autoradiographic, and immunocytochemical analysis. Viable HiB5 cell grafts were identified in all animals, together with reactive microglia and macrophages located throughout the periinjured parenchyma and grafts (OX-42 immunohistochemistry). Brain-injured animals transplanted with either NGF-HiB5 or n-HiB5 cells displayed significantly improved neuromotor function (p < 0.05) and spatial learning behavior (p < 0.005) compared with brain-injured animals receiving microinjections of vehicle alone. A significant reduction in hippocampal CA3 cell death was observed in brain-injured animals receiving transplants of NGF-HiB5 cells compared with those receiving n-HiB5 cells or vehicle (p < 0.025). CONCLUSIONS: This study demonstrates that immortalized neural stem cells that have been retrovirally transduced to produce NGF can markedly improve cognitive and neuromotor function and rescue hippocampal CA3 neurons when transplanted into the injured brain during the acute posttraumatic period.
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| 16. |
- Robba, Chiara, et al.
(författare)
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Oxygen targets and 6-month outcome after out of hospital cardiac arrest : a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial
- 2022
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.
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| 17. |
- Robba, Chiara, et al.
(författare)
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Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients : a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
- 2022
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 48:8, s. 1024-1038
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2–8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5–9) cmH20, plateau pressure was 20 cmH20 (IQR = 17–23), driving pressure was 12 cmH20 (IQR = 10–15), mechanical power 16.2 J/min (IQR = 12.1–21.8), ventilatory ratio was 1.27 (IQR = 1.04–1.6), and respiratory rate was 17 breaths/minute (IQR = 14–20). Median partial pressure of oxygen was 87 mmHg (IQR = 75–105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36–45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003–1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001–1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. Conclusions: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.
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| 18. |
- Rytter, Anna, et al.
(författare)
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The temperature dependence and involvement of mitochondria permeability transition and caspase activation in damage to organotypic hippocampal slices following in vitro ischemia.
- 2005
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Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 95:4, s. 1108-1117
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Tidskriftsartikel (refereegranskat)abstract
- The aggravating effect of hyperglycemia on ischemic brain injury can be mimicked in a model of in vitro ischemia (IVI) using murine hippocampal slice cultures. Using this model, we found that the damage in the CA1 region following IVI in the absence or presence of 40 mM glucose (hyperglycemia) is highly temperature dependent. Decreasing the temperature from 35 to 31 degrees C during IVI prevented cell death, whereas increasing the temperature by 2 degrees C markedly aggravated damage. As blockade of the mitochondrial permeability transition (MPT) is equally effective as hypothermia in preventing ischemic cell death in vivo, we investigated whether inhibition of MPT or of caspases was protective following IVI. In the absence of glucose, the MPT blockers cyclosporin A and MeIle(4)-CsA but not the immunosuppressive compound FK506 diminished cell death. In contrast, following hyperglycemic IVI, MPT blockade was ineffective. Also, the pan-caspase inhibitor Boc-Asp(OMe)fluoromethyl ketone did not decrease cell death in the CA1 region following IVI or hyperglycemic IVI. We conclude that cell death in the CA1 region of organotypic murine hippocampal slices following IVI is highly temperature dependent and involves MPT. In contrast, cell death following hyperglycemic IVI, although completely prevented by hypothermia, is not mediated by mechanisms that involve MPT or caspase activation
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| 19. |
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| 20. |
- Teilum, Maria, et al.
(författare)
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Hypothermia Affects Translocation of Numerous Cytoplasmic Proteins Following Global Cerebral Ischemia.
- 2007
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:7, s. 2822-2832
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Tidskriftsartikel (refereegranskat)abstract
- Using a decapitation ischemia model, we studied translocation of proteins to and from the cytosol in normothermic (NT) and hypothermic (HT) rat brains. 2D gel analysis identified 74 proteins whose cytosolic level changed significantly after 15 min of ischemia. HT preserved the cytosolic levels of several glycolytic enzymes, as well as many plasticity related proteins, otherwise decreased following NT ischemia. The levels of redox-related proteins was lower in HT than in NT. Our results indicate that translocation of proteins to and from the cytosol is an important issue during ischemia.
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| 21. |
- Tomasevic, Gregor, et al.
(författare)
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Delayed neuromotor recovery and increased memory acquisition dysfunction following experimental brain trauma in mice lacking the DNA repair gene XPA.
- 2012
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Ingår i: Journal of Neurosurgery. - 0022-3085. ; 116:6, s. 1368-1378
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Tidskriftsartikel (refereegranskat)abstract
- Object: This study investigates the outcome after traumatic brain injury (TBI) in mice lacking the essential DNA repair gene xeroderma pigmentosum group A (XPA). As damage to DNA has been implicated in neuronal cell death in various models, the authors sought to elucidate whether the absence of an essential DNA repair factor would affect the outcome of TBI in an experimental setting. Methods: Thirty-seven adult mice of either wild-type (n = 18) or XPA-deficient ("knock-out" [n = 19]) genotype were subjected to controlled cortical impact experimental brain trauma, which produced a focal brain injury. Sham-injured mice of both genotypes were used as controls (9 in each group). The mice were subjected to neurobehavoral tests evaluating learning/acquisition (Morris water maze) and motor dysfunction (Rotarod and composite neuroscore test), pre- and postinjury up to 4 weeks. The mice were killed after 1 or 4 weeks, and cortical lesion volume, as well as hippocampal and thalamic cell loss, was evaluated. Hippocampal staining with doublecortin antibody was used to evaluate neurogenesis after the insult. Results: Brain-injured XPA(-/-) mice exhibited delayed recovery from impairment in neurological motor function, as well as pronounced cognitive dysfunction in a spatial learning task (Morris water maze), compared with injured XPA(+/+) mice (p < 0.05). No differences in cortical lesion volume, hippocampal damage, or thalamic cell loss were detected between XPA(+/+) and XPA(-/-) mice after brain injury. Also, no difference in the number of cells stained with doublecortin in the hippocampus was detected. Conclusions: The authors' results suggest that lack of the DNA repair factor XPA may delay neurobehavioral recovery after TBI, although they do not support the notion that this DNA repair deficiency results in increased cell or tissue death in the posttraumatic brain.
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| 22. |
- Wieloch, Tadeusz, et al.
(författare)
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Mitochondrial Permeability Transition in the CNS - Composition, Regulation, and Pathophysiological Relevance
- 2007
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Ingår i: Handbook of Neurochemistry and Molecular Neurobiology - Brain Energetics. Integration of Molecular and Cellular Processes. - Boston, MA : Springer US. - 9780387303666 ; , s. 667-702
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Mitochondrial permeability transition (MPT) is induced in isolated brain mitochondria by calcium and oxidants and is inhibited by adenine nucleotides. When induced, MPT is associated with equilibration of solutes of <1500 Da across the inner mitochondrial membrane. A persistent induction of MPT depolarizes the inner membrane and causes cessation of ATP synthesis, swelling of the matrix, and bursting of the mitochondrial membranes. The rupture of the membranes releases calcium stored in the mitochondrial matrix and apoptogenic factors from the intermembrane space, leading to cell death. MPT has been implicated in acute brain injury and neurodegenerative disease since inhibitors of MPT such as cyclosporin A (CsA) are brain protective. Whether MPT has a physiological role is unclear, but MPT may be important in calcium homeostasis under conditions of excessive neuronal activity.
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