In Vivo Studies of Brain Oxygen Metabolism and Oxidative Phosphorylation

Author(s):  
Xiao-Hong Zhu ◽  
Wei Chen
2003 ◽  
pp. 251-253 ◽  
Author(s):  
Atsushi Sakurai ◽  
K. Kinoshita ◽  
T. Atsumi ◽  
T. Moriya ◽  
A. Utagawa ◽  
...  

Gut ◽  
1997 ◽  
Vol 41 (3) ◽  
pp. 344-353 ◽  
Author(s):  
S Somasundaram ◽  
S Rafi ◽  
J Hayllar ◽  
G Sigthorsson ◽  
M Jacob ◽  
...  

Background—The “topical” effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage.Aim—To examine the possible mechanism of the “topical” phase of damage in the small intestine.Methods—Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg). The effect of conventional and non-acidic NSAIDs on rat liver mitochondrial respiration was measured in vitro in a Clarke-type oxygen electrode.Results—The subcellular organelle marker enzymes showed mitochondrial and brush border involvement within an hour of indomethacin administration. Electron microscopy showed dose dependent mitochondrial changes following indomethacin administration consistent with uncoupling of oxidative phosphorylation (or inhibition of electron transport) which were indistinguishable from those seen with the uncoupler dinitrophenol. Parenteral indomethacin caused similar changes, but not in rats with ligated bile ducts. A range of NSAIDs, but not paracetamol or non-acidic NSAIDs which have a favourable gastrointestinal tolerability profile, uncoupled oxidative phosphorylation in vitro at micromolar concentrations and inhibited respiration at higher concentrations. In vivo studies with nabumetone and aspirin further suggested that uncoupling or inhibition of electron transport underlies the “topical” phase of NSAID induced damage.Conclusion—Collectively, these studies suggest that NSAID induced changes in mitochondrial energy production may be an important component of the “topical” phase of damage induction.


PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
Author(s):  
Valerie E. M. Griffeth ◽  
Nicholas P. Blockley ◽  
Aaron B. Simon ◽  
Richard B. Buxton

2007 ◽  
Vol 106 (4) ◽  
pp. 526-529 ◽  
Author(s):  
Michael N. Diringer ◽  
Venkatesh Aiyagari ◽  
Allyson R. Zazulia ◽  
Tom O. Videen ◽  
William J. Powers

Object Recent observations indicate that traumatic brain injury (TBI) may be associated with mitochondrial dysfunction. This, along with growing use of brain tissue PO2 monitors, has led to considerable interest in the potential use of ventilation with 100% oxygen to treat patients who have suffered a TBI. To date, the impact of normobaric hyperoxia has only been evaluated using indirect measures of its impact on brain metabolism. To determine if normobaric hyperoxia improves brain oxygen metabolism following acute TBI, the authors directly measured the cerebral metabolic rate for oxygen (CMRO2) with positron emission tomography before and after ventilation with 100% oxygen. Methods Baseline measurements of arterial and jugular venous blood gases, mean arterial blood pressure, intracranial pressure, cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction, and CMRO2 were made at baseline while the patients underwent ventilation with a fraction of inspired oxygen (FiO2) of 0.3 to 0.5. The FiO2 was then increased to 1.0, and 1 hour later all measurements were repeated. Five patients were studied a mean of 17.9 ±5.8 hours (range 12–23 hours) after trauma. The median admission Glasgow Coma Scale score was 7 (range 3–9). During ventilation with 100% oxygen, there was a marked rise in PaO2 (from 117 ± 31 to 371 ± 99 mm Hg, p < 0.0001) and a small rise in arterial oxygen content (12.7 ± 4.0 to 13.3 ± 4.6 vol %, p = 0.03). There were no significant changes in systemic hemodynamic or other blood gas measurements. At the baseline evaluation, bihemispheric CBF was 39 ± 12 ml/100 g/min and bihemispheric CMRO2 was 1.9 ± 0.6 ml/100 g/min. During hyperoxia there was no significant change in either of these measurements. (Values are given as the mean ± standard deviation throughout.) Conclusions Normobaric hyperoxia did not improve brain oxygen metabolism. In the absence of outcome data from clinical trials, these preliminary data do not support the use of 100% oxygen in patients with acute TBI, although larger confirmatory studies are needed.


2017 ◽  
Vol 38 (9) ◽  
pp. 1481-1499 ◽  
Author(s):  
Weili Lin ◽  
William J Powers

Gaining insights into brain oxygen metabolism has been one of the key areas of research in neurosciences. Extensive efforts have been devoted to developing approaches capable of providing measures of brain oxygen metabolism not only under normal physiological conditions but, more importantly, in various pathophysiological conditions such as cerebral ischemia. In particular, quantitative measures of cerebral metabolic rate of oxygen using positron emission tomography (PET) have been shown to be capable of discerning brain tissue viability during ischemic insults. However, the complex logistics associated with oxygen-15 PET have substantially hampered its wide clinical applicability. In contrast, magnetic resonance imaging (MRI)-based approaches have provided quantitative measures of cerebral oxygen metabolism similar to that obtained using PET. Given the wide availability, MRI-based approaches may have broader clinical impacts, particularly in cerebral ischemia, when time is a critical factor in deciding treatment selection. In this article, we review the pathophysiological basis of altered cerebral hemodynamics and oxygen metabolism in cerebral ischemia, how quantitative measures of cerebral metabolism were obtained using the Kety–Schmidt approach, the physical concepts of non-invasive oxygen metabolism imaging approaches, and, finally, clinical applications of the discussed imaging approaches.


NeuroImage ◽  
2017 ◽  
Vol 155 ◽  
pp. 331-343 ◽  
Author(s):  
Alberto Merola ◽  
Michael A. Germuska ◽  
Esther AH Warnert ◽  
Lewys Richmond ◽  
Daniel Helme ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document