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Georg Oeltzschner - One of the best experts on this subject based on the ideXlab platform.
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Covert hepatic encephalopathy: elevated total glutathione and absence of Brain Water content changes
Metabolic Brain Disease, 2016Co-Authors: Georg Oeltzschner, Markus Butz, Frithjof Wickrath, Hans-jörg Wittsack, Alfons SchnitzlerAbstract:Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild Brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local Brain Water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy (^1H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI Brain Water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P
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Use of quantitative Brain Water imaging as concentration reference for J-edited MR spectroscopy of GABA
Magnetic resonance imaging, 2016Co-Authors: Georg Oeltzschner, Frithjof Wickrath, Alfons Schnitzler, Helge J. Zöllner, Hans-jörg WittsackAbstract:Abstract Purpose To compare two different methods of obtaining the Water reference for determination of quantitative Water-scaled in vivo concentration estimates of γ-aminobutyric acid (GABA). Methods Water-scaled GABA estimates from localized J-difference edited MR spectroscopy experiments can be computed using standard values for tissue-specific Water content and relaxation times. Water content and relaxation may, however, be altered in pathology. This work re-analyzed data from a recent study in healthy controls and patients with minimal (mHE) or grade I (HE 1) hepatic encephalopathy, a disease associated with slight elevation of Brain Water content. J-difference edited MR spectroscopy data were combined with quantitative Brain Water measures, which provided individual Water density references and T 1 relaxation times. Resulting GABA estimates were compared to concentration values obtained using standard tissue-specific Water content and relaxation values. Results Occipital GABA concentration values obtained from individual Water and T 1 maps were 1.64 ± 0.35 mM in controls, and significantly higher ( P P Conclusion Water-scaled in vivo GABA estimates can be obtained with individual Water density and T 1 relaxation mapping. This approach may be useful for studying GABA levels in pathologies with substantial Brain Water content or relaxation changes.
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Magnetic resonance spectroscopy and quantitative Brain Water imaging in patients with hepatic encephalopathy
2016Co-Authors: Georg OeltzschnerAbstract:Hepatic encephalopathy (HE) is a set of neurological symptoms frequently occurring as a consequence of liver cirrhosis. HE affects many functional entities of the Brain, including cognitive, executive and perceptive systems. Patients with HE exhibit an impaired performance of cognitive tasks, abnormal perception of temperature stimuli, behavioural changes, and motor dysfunctions. The severity of these symptoms is highly volatile and can range from subtle alterations to stupor and coma hepaticum. The accumulation of neurotoxic ammonia in the Brain due to impaired liver activity has been identified as a key feature of HE, triggering manifold responses such as neuroinflammation, oxidative stress, and formation of low-grade oedema. Recent magnetoencephalography (MEG) studies have provided evidence that HE symptoms are consistently associated with slowing of neural oscillations in their respective functional systems, but the underlying mechanisms remain elusive. While these and numerous other processes behind HE have been identified on microscopic and mesoscopic scales, they are yet to be integrated into a coherent pathophysiological concept, and at this point, it remains unclear how they contribute to pathological neural activity. The present work investigated the role of the main inhibitory neurotransmitter gamma-aminobutyric acid (GABA) for the pathogenesis of HE. As local GABA levels had previously been shown to influence the frequency of oscillations in the visual and the motor gamma frequency band, it was hypothesized that altered GABA concentrations contribute to HE symptoms via modulation of neural oscillations. To test this hypothesis, magnetic resonance spectroscopy (MRS) was employed to determine in vivo levels of GABA in a cohort of 16 healthy controls and 30 HE patients. Results showed a decrease of GABA in the visual cortex in HE. Further, individual GABA levels correlated with the critical flicker frequency (CFF), a singular experimental parameter reliably reflecting HE severity. Low GABA was also linked to elevated blood ammonia levels. Beyond this, GABA was coupled to concentrations of glutamine and myo-inositole, two compounds that are highly involved in astrocytic regulation of hyperammonemia. However, none of these relationships became evident in the sensorimotor region, giving rise to the assumption that the mechanisms mediating pathological behaviour are substantially different across Brain regions. In a second MRS investigation, the interplay of the major cerebral antioxidant glutathione, magnetic resonance imaging (MRI) measures of Brain Water content and HE characteristics was studied. Glutathione was elevated in HE, correlated with blood ammonia levels and closely followed alterations of glutamine and myo-inositol, suggesting an involvement in the interception of oxidative stress induced by ammonia. In contrast, measures of Brain Water content were not influenced by HE severity, blood ammonia or metabolite concentrations. This may imply that, at least in early stages of HE, the pathological impact of cerebral oedema may be smaller than previously assumed. In conclusion, the novel findings presented in this work may help improve the understanding of the emergence of HE. GABA concentrations are presumably relevant for the development of HE symptoms in certain functional systems, but evidence prompts the notion that the exact pathways mediating abnormal oscillatory behaviour are highly region-specific. Further, glutathione appears to participate in the adaptation to hyperammonemia, whereas the relationship of Brain Water content and HE severity may be of more complex nature than previously expected.
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Covert hepatic encephalopathy: elevated total glutathione and absence of Brain Water content changes
Metabolic brain disease, 2015Co-Authors: Georg Oeltzschner, Markus Butz, Frithjof Wickrath, Hans-jörg Wittsack, Alfons SchnitzlerAbstract:Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild Brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local Brain Water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy (1H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI Brain Water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P < 0.001). It was further linked to Gln/Cr and mI/Cr (P < 0.01 in visual, P < 0.001 in sensorimotor) and to GABA/Cr (P < 0.01 in visual). Visual GSx/Cr correlated with Brain Water content in the thalamus, nucleus caudatus, and visual cortex (P < 0.01). Brain Water measures did neither show group effects nor correlations with CFF or blood ammonia. Elevated total glutathione levels in covert HE (< HE 2) correlate with blood ammonia and may be a regional-specific reaction to hyperammonemia and oxidative stress. Brain Water content is locally linked to visual glutathione levels, but appears not to be associated with changes of clinical parameters. This might suggest that cerebral oedema is only marginally responsible for the symptoms of covert HE.
Alfons Schnitzler - One of the best experts on this subject based on the ideXlab platform.
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Covert hepatic encephalopathy: elevated total glutathione and absence of Brain Water content changes
Metabolic Brain Disease, 2016Co-Authors: Georg Oeltzschner, Markus Butz, Frithjof Wickrath, Hans-jörg Wittsack, Alfons SchnitzlerAbstract:Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild Brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local Brain Water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy (^1H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI Brain Water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P
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Use of quantitative Brain Water imaging as concentration reference for J-edited MR spectroscopy of GABA
Magnetic resonance imaging, 2016Co-Authors: Georg Oeltzschner, Frithjof Wickrath, Alfons Schnitzler, Helge J. Zöllner, Hans-jörg WittsackAbstract:Abstract Purpose To compare two different methods of obtaining the Water reference for determination of quantitative Water-scaled in vivo concentration estimates of γ-aminobutyric acid (GABA). Methods Water-scaled GABA estimates from localized J-difference edited MR spectroscopy experiments can be computed using standard values for tissue-specific Water content and relaxation times. Water content and relaxation may, however, be altered in pathology. This work re-analyzed data from a recent study in healthy controls and patients with minimal (mHE) or grade I (HE 1) hepatic encephalopathy, a disease associated with slight elevation of Brain Water content. J-difference edited MR spectroscopy data were combined with quantitative Brain Water measures, which provided individual Water density references and T 1 relaxation times. Resulting GABA estimates were compared to concentration values obtained using standard tissue-specific Water content and relaxation values. Results Occipital GABA concentration values obtained from individual Water and T 1 maps were 1.64 ± 0.35 mM in controls, and significantly higher ( P P Conclusion Water-scaled in vivo GABA estimates can be obtained with individual Water density and T 1 relaxation mapping. This approach may be useful for studying GABA levels in pathologies with substantial Brain Water content or relaxation changes.
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Covert hepatic encephalopathy: elevated total glutathione and absence of Brain Water content changes
Metabolic brain disease, 2015Co-Authors: Georg Oeltzschner, Markus Butz, Frithjof Wickrath, Hans-jörg Wittsack, Alfons SchnitzlerAbstract:Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild Brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local Brain Water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy (1H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI Brain Water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P < 0.001). It was further linked to Gln/Cr and mI/Cr (P < 0.01 in visual, P < 0.001 in sensorimotor) and to GABA/Cr (P < 0.01 in visual). Visual GSx/Cr correlated with Brain Water content in the thalamus, nucleus caudatus, and visual cortex (P < 0.01). Brain Water measures did neither show group effects nor correlations with CFF or blood ammonia. Elevated total glutathione levels in covert HE (< HE 2) correlate with blood ammonia and may be a regional-specific reaction to hyperammonemia and oxidative stress. Brain Water content is locally linked to visual glutathione levels, but appears not to be associated with changes of clinical parameters. This might suggest that cerebral oedema is only marginally responsible for the symptoms of covert HE.
Hans-jörg Wittsack - One of the best experts on this subject based on the ideXlab platform.
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Covert hepatic encephalopathy: elevated total glutathione and absence of Brain Water content changes
Metabolic Brain Disease, 2016Co-Authors: Georg Oeltzschner, Markus Butz, Frithjof Wickrath, Hans-jörg Wittsack, Alfons SchnitzlerAbstract:Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild Brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local Brain Water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy (^1H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI Brain Water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P
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Use of quantitative Brain Water imaging as concentration reference for J-edited MR spectroscopy of GABA
Magnetic resonance imaging, 2016Co-Authors: Georg Oeltzschner, Frithjof Wickrath, Alfons Schnitzler, Helge J. Zöllner, Hans-jörg WittsackAbstract:Abstract Purpose To compare two different methods of obtaining the Water reference for determination of quantitative Water-scaled in vivo concentration estimates of γ-aminobutyric acid (GABA). Methods Water-scaled GABA estimates from localized J-difference edited MR spectroscopy experiments can be computed using standard values for tissue-specific Water content and relaxation times. Water content and relaxation may, however, be altered in pathology. This work re-analyzed data from a recent study in healthy controls and patients with minimal (mHE) or grade I (HE 1) hepatic encephalopathy, a disease associated with slight elevation of Brain Water content. J-difference edited MR spectroscopy data were combined with quantitative Brain Water measures, which provided individual Water density references and T 1 relaxation times. Resulting GABA estimates were compared to concentration values obtained using standard tissue-specific Water content and relaxation values. Results Occipital GABA concentration values obtained from individual Water and T 1 maps were 1.64 ± 0.35 mM in controls, and significantly higher ( P P Conclusion Water-scaled in vivo GABA estimates can be obtained with individual Water density and T 1 relaxation mapping. This approach may be useful for studying GABA levels in pathologies with substantial Brain Water content or relaxation changes.
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Covert hepatic encephalopathy: elevated total glutathione and absence of Brain Water content changes
Metabolic brain disease, 2015Co-Authors: Georg Oeltzschner, Markus Butz, Frithjof Wickrath, Hans-jörg Wittsack, Alfons SchnitzlerAbstract:Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild Brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local Brain Water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy (1H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI Brain Water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P < 0.001). It was further linked to Gln/Cr and mI/Cr (P < 0.01 in visual, P < 0.001 in sensorimotor) and to GABA/Cr (P < 0.01 in visual). Visual GSx/Cr correlated with Brain Water content in the thalamus, nucleus caudatus, and visual cortex (P < 0.01). Brain Water measures did neither show group effects nor correlations with CFF or blood ammonia. Elevated total glutathione levels in covert HE (< HE 2) correlate with blood ammonia and may be a regional-specific reaction to hyperammonemia and oxidative stress. Brain Water content is locally linked to visual glutathione levels, but appears not to be associated with changes of clinical parameters. This might suggest that cerebral oedema is only marginally responsible for the symptoms of covert HE.
Thomas J. K. Toung - One of the best experts on this subject based on the ideXlab platform.
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Effects of Volume Replacement for Urinary Losses from Mannitol Diuresis on Brain Water in Normal Rats
Neurocritical Care, 2020Co-Authors: Allan Gottschalk, Thomas J. K. ToungAbstract:Background/Objective It is frequently recommended that urine output following perioperative mannitol administration be replaced 1:1 with an isotonic crystalloid solution. It is possible that this strategy could increase Brain Water by reducing the serum osmolality achieved with prior mannitol administration. Therefore, Brain Water content of rats treated with mannitol alone or mannitol plus normal saline (NS) was studied over a range of urinary replacement ratios. Methods Male Wister rats received mannitol 3.2 gm/100 gm infused over 45 min followed by hourly determinations of urine output (UO). Control animals received no additional therapy, whereas animals undergoing intervention received hourly replacement of their urinary losses with 0.9% NS in decreasing NS:UO ratios (1:1, 1:2, 1:3). Three hours after completion of the mannitol infusion, a final tally of UO was made. At that time in all animals, blood was obtained for determination of hemoglobin and electrolyte concentrations and plasma osmolality. Following that, the animals were sacrificed to determine Brain Water content. Additional groups underwent the same protocol but for 5 h with 1:1 urinary replacement, or received a volume of NS equal to that of the mannitol administered to all other control and intervention animals. Results 1:1 replacement of urinary loss with NS following mannitol administration was associated with Brain Water content indistinguishable from control animals receiving only a volume of NS equal to that of the mannitol administered to all other groups. Regression analysis demonstrated a decrease in the final Brain Water content of 0.67% (CI95 0.43–0.92, p
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Comparison of equivolume, equiosmolar solutions of mannitol and hypertonic saline with or without furosemide on Brain Water content in normal rats.
Anesthesiology, 2013Co-Authors: Liang Chao Wang, Allan Gottschalk, Alexander Papangelou, Christopher Lin, Marek A. Mirski, Thomas J. K. ToungAbstract:BACKGROUND Mannitol and hypertonic saline (HS) are used by clinicians to reduce Brain Water and intracranial pressure and have been evaluated in a variety of experimental and clinical protocols. Administering equivolume, equiosmolar solutions in healthy animals could help produce fundamental data on Water translocation in uninjured tissue. Furthermore, the role of furosemide as an adjunct to osmotherapy remains unclear. METHODS Two hundred twenty isoflurane-anesthetized rats were assigned randomly to receive equivolume normal saline, 4.2% HS (1,368 mOsm/L 25% mannitol (1,375 mOsm/L), normal saline plus furosemide (8 mg/kg), or 4.2% HS plus furosemide (8 mg/kg) over 45 min. Rats were killed at 1, 2, 3, and 5 h after completion of the primary infusion. Outcome measurements included body weight; urinary output; serum and urinary osmolarity and electrolytes; and Brain, lung, skeletal muscle, and small bowel Water content. RESULTS In the mannitol group, the mean Water content of Brain tissue during the experiment was 78.0% (99.3% CI, 77.9-78.2%), compared to results from the normal saline (79.3% [99.3% CI, 79.1-79.5%]) and HS (78.8% [99.3% CI, 78.6-78.9%]) groups (P < 0.001), whereas HS plus furosemide yielded 78.0% (99.3% CI, 77.8-78.2%) (P = 0.917). After reaching a nadir at 1 h, Brain Water content increased at similar rates for mannitol (0.27%/h [99.3% CI, 0.14-0.40%/h]) and HS (0.27%/h [99.3% CI, 0.17-0.37%/h]) groups (P = 0.968). CONCLUSIONS When compared to equivolume, equiosmolar administration of HS, mannitol reduced Brain Water content to a greater extent over the entire course of the 5-h experiment. When furosemide was added to HS, the Brain-dehydrating effect could not be distinguished from that of mannitol.
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global Brain Water increases after experimental focal cerebral ischemia effect of hypertonic saline
Critical Care Medicine, 2002Co-Authors: Thomas J. K. Toung, Patricia D Hurn, Richard J Traystman, Anish BhardwajAbstract:OBJECTIVE Isolated experiments suggest that global cerebral edema is a sequela of large hemispheric ischemic lesions, presumably as an extension of the initial ischemic insult into areas of vital, noninjured tissue. Diuretics and osmotic agents are controversial and poorly defined therapeutic modalities after large infarction. By using a rat model of middle cerebral artery occlusion (MCAO), we tested the hypothesis that significant edema occurs in the contralateral uninjured hemisphere and that this postischemic complication can be manipulated by hypertonic saline therapy. DESIGN Prospective laboratory animal study. SETTING Research laboratory in a teaching hospital. SUBJECTS Halothane-anesthetized, male Wistar rats. INTERVENTIONS Under controlled conditions of normoxia, normocarbia, and normothermia, rats were subjected to 2 hrs of MCAO. MEASUREMENTS AND MAIN RESULTS Adequacy of MCAO and reperfusion was assessed by laser Doppler flowmetry. All animals except naive rats received continuous infusion of 0.9% saline at 0.5 mL/hr throughout the experiment. Brains were harvested, and tissue Water content was estimated by comparing the wet-to-dry weight ratios of ipsilateral and contralateral cerebral hemispheres at 12 hrs, 24 hrs, or 2, 3, or 7 days postischemia. Naive and sham-operated rats served as control cohorts. In a second series of randomized experiments, wet-to-dry weight ratios were determined in rats treated with continuous intravenous infusion of 7.5% hypertonic saline (0.5 mL/hr; acetate/chloride, 50:50) and were compared with well-studied antiedema therapy: 20% mannitol (2.5 g/kg bolus every 6 hrs) or furosemide (2.5 mg/kg bolus every 6 hrs). Treatments were started at 24 hrs of reperfusion, and Brain Water was assessed at 2 days of reperfusion. In a third series of experiments, wet-to-dry ratios were determined in Brains harvested at 2 days of reperfusion from rats that were subjected to 2 hrs of MCAO and did not receive any intravenous fluids. All values are mean +/- SEM. There were no differences between sham-operated and naive control cohorts. At 24 hrs of reperfusion, Water content was higher in both ipsilateral ischemic (82.80 +/- 0.86%) and contralateral hemispheres (80.53 +/- 0.29%), compared with naive animals (ipsilateral, 79.62 +/- 0.12%; contralateral, 79.53 +/- 0.13%). Maximal cerebral edema was measured at 2 days in both hemispheres (ipsilateral, 83.94 +/- 0.47%; contralateral, 80.63 +/- 0.13%). Edema was present for up to 3 days in contralateral tissue (80.27 +/- 0.26%) and persisted to 7 days in the injured hemisphere (81.07 +/- 0.34%). Maximal edema (as assessed at 2 days postocclusion) was robustly attenuated with hypertonic saline therapy (ipsilateral, 81.59 +/- 0.52%; contralateral, 78.44 +/- 0.22%). The efficacy of hypertonic saline was equivalent to furosemide (ipsilateral, 82.09 +/- 0.50%; contralateral, 79.13 +/- 0.17%) but less robust than mannitol (ipsilateral, 79.89 +/- 0.36%; contralateral, 78.73 +/- 0.17%). CONCLUSIONS These data demonstrate that cerebral edema persists in both injured and contralateral hemispheres for days after MCAO. The global, maximal increase in Brain Water is responsive to continuous 7.5% hypertonic saline treatment begun at 24 hrs postischemia and to standard diuretic/osmotic agents. These results may have implications for diuretic and osmotic therapy in clinical ischemic stroke.
Frithjof Wickrath - One of the best experts on this subject based on the ideXlab platform.
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Covert hepatic encephalopathy: elevated total glutathione and absence of Brain Water content changes
Metabolic Brain Disease, 2016Co-Authors: Georg Oeltzschner, Markus Butz, Frithjof Wickrath, Hans-jörg Wittsack, Alfons SchnitzlerAbstract:Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild Brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local Brain Water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy (^1H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI Brain Water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P
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Use of quantitative Brain Water imaging as concentration reference for J-edited MR spectroscopy of GABA
Magnetic resonance imaging, 2016Co-Authors: Georg Oeltzschner, Frithjof Wickrath, Alfons Schnitzler, Helge J. Zöllner, Hans-jörg WittsackAbstract:Abstract Purpose To compare two different methods of obtaining the Water reference for determination of quantitative Water-scaled in vivo concentration estimates of γ-aminobutyric acid (GABA). Methods Water-scaled GABA estimates from localized J-difference edited MR spectroscopy experiments can be computed using standard values for tissue-specific Water content and relaxation times. Water content and relaxation may, however, be altered in pathology. This work re-analyzed data from a recent study in healthy controls and patients with minimal (mHE) or grade I (HE 1) hepatic encephalopathy, a disease associated with slight elevation of Brain Water content. J-difference edited MR spectroscopy data were combined with quantitative Brain Water measures, which provided individual Water density references and T 1 relaxation times. Resulting GABA estimates were compared to concentration values obtained using standard tissue-specific Water content and relaxation values. Results Occipital GABA concentration values obtained from individual Water and T 1 maps were 1.64 ± 0.35 mM in controls, and significantly higher ( P P Conclusion Water-scaled in vivo GABA estimates can be obtained with individual Water density and T 1 relaxation mapping. This approach may be useful for studying GABA levels in pathologies with substantial Brain Water content or relaxation changes.
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Covert hepatic encephalopathy: elevated total glutathione and absence of Brain Water content changes
Metabolic brain disease, 2015Co-Authors: Georg Oeltzschner, Markus Butz, Frithjof Wickrath, Hans-jörg Wittsack, Alfons SchnitzlerAbstract:Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild Brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local Brain Water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy (1H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI Brain Water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P < 0.001). It was further linked to Gln/Cr and mI/Cr (P < 0.01 in visual, P < 0.001 in sensorimotor) and to GABA/Cr (P < 0.01 in visual). Visual GSx/Cr correlated with Brain Water content in the thalamus, nucleus caudatus, and visual cortex (P < 0.01). Brain Water measures did neither show group effects nor correlations with CFF or blood ammonia. Elevated total glutathione levels in covert HE (< HE 2) correlate with blood ammonia and may be a regional-specific reaction to hyperammonemia and oxidative stress. Brain Water content is locally linked to visual glutathione levels, but appears not to be associated with changes of clinical parameters. This might suggest that cerebral oedema is only marginally responsible for the symptoms of covert HE.