Skip to main content
Top
Published in: Medical Gas Research 1/2014

Open Access 01-12-2014 | Research

Extended normobaric hyperoxia therapy yields greater neuroprotection for focal transient ischemia-reperfusion in rats

Authors: Zhongrui Yuan, Rong Pan, Wenlan Liu, Ke Jian Liu

Published in: Medical Gas Research | Issue 1/2014

Login to get access

Abstract

Background

Normobaric hyperoxia (NBO) therapy is neuroprotective in acute ischemic stroke. However, how long the NBO should last to obtain optimal outcome is still unclear. Reports show that ischemic penumbra blood supply may remain compromised for a long period after ischemia-reperfusion, which would impair tissue oxygenation in ischemic penumbra. Therefore, we hypothesized that longer-lasting NBO may yield greater neuroprotection.

Methods

The relationship between treatment outcome and NBO duration was examined in this study. Rats were subjected to 90 min middle cerebral artery occlusion followed by reperfusion for 22.5 hours. NBO started at 30 min post ischemia and lasted for 2, 4 or 8 h. Treatment efficacy was evaluated by measuring infarction volume, oxidative stress and apoptosis.

Results

Among 2 h, 4 h and 8 h NBO, 8 h NBO offered the greatest efficacy in reducing 24-hour infarction volume, attenuating oxidative stress that was indicated by decreased production of 8-hydroxydeoxyguanosine and NADPH oxidase catalytic subunit gp91phox, and alleviating apoptosis that was associated with reduced production of DNA fragment and caspase-3 activity in cortex penumbra.

Conclusions

Under our experimental conditions, longer duration of NBO treatment produced greater benefits in focal transient cerebral ischemia-reperfusion rats.
Appendix
Available only for authorised users
Literature
1.
go back to reference Flynn EP, Auer RN: Eubaric hyperoxemia and experimental cerebral infarction. Ann Neurol. 2002, 52 (5): 566-572.CrossRefPubMed Flynn EP, Auer RN: Eubaric hyperoxemia and experimental cerebral infarction. Ann Neurol. 2002, 52 (5): 566-572.CrossRefPubMed
3.
go back to reference Henninger N, Bouley J, Nelligan JM, Sicard KM, Fisher M: Normobaric hyperoxia delays perfusion/diffusion mismatch evolution, reduces infarct volume, and differentially affects neuronal cell death pathways after suture middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab. 2007, 27 (9): 1632-1642.CrossRefPubMed Henninger N, Bouley J, Nelligan JM, Sicard KM, Fisher M: Normobaric hyperoxia delays perfusion/diffusion mismatch evolution, reduces infarct volume, and differentially affects neuronal cell death pathways after suture middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab. 2007, 27 (9): 1632-1642.CrossRefPubMed
4.
go back to reference Liu W, Chen Q, Liu J, Liu KJ: Normobaric hyperoxia protects the blood brain barrier through inhibiting Nox2 containing NADPH oxidase in ischemic stroke. Med Gas Res. 2011, 1 (1): 22-PubMedCentralCrossRefPubMed Liu W, Chen Q, Liu J, Liu KJ: Normobaric hyperoxia protects the blood brain barrier through inhibiting Nox2 containing NADPH oxidase in ischemic stroke. Med Gas Res. 2011, 1 (1): 22-PubMedCentralCrossRefPubMed
5.
go back to reference Esposito E, Mandeville ET, Hayakawa K, Singhal AB, Lo EH: Effects of normobaric oxygen on the progression of focal cerebral ischemia in rats. Exp Neurol. 2013, 249: 33-38.PubMedCentralCrossRefPubMed Esposito E, Mandeville ET, Hayakawa K, Singhal AB, Lo EH: Effects of normobaric oxygen on the progression of focal cerebral ischemia in rats. Exp Neurol. 2013, 249: 33-38.PubMedCentralCrossRefPubMed
6.
go back to reference Singhal AB, Ratai E, Benner T, Vangel M, Lee V, Koroshetz WJ, Schaefer PW, Sorensen AG, Gonzalez RG: Magnetic resonance spectroscopy study of oxygen therapy in ischemic stroke. Stroke. 2007, 38 (10): 2851-2854.CrossRefPubMed Singhal AB, Ratai E, Benner T, Vangel M, Lee V, Koroshetz WJ, Schaefer PW, Sorensen AG, Gonzalez RG: Magnetic resonance spectroscopy study of oxygen therapy in ischemic stroke. Stroke. 2007, 38 (10): 2851-2854.CrossRefPubMed
7.
go back to reference Chiu EH, Liu CS, Tan TY, Chang KC: Venturi mask adjuvant oxygen therapy in severe acute ischemic stroke. Arch Neurol. 2006, 63 (5): 741-744.CrossRefPubMed Chiu EH, Liu CS, Tan TY, Chang KC: Venturi mask adjuvant oxygen therapy in severe acute ischemic stroke. Arch Neurol. 2006, 63 (5): 741-744.CrossRefPubMed
8.
go back to reference Padma MV, Bhasin A, Bhatia R, Garg A, Singh MB, Tripathi M, Prasad K: Normobaric oxygen therapy in acute ischemic stroke: a pilot study in Indian patients. Ann Indian Acad Neurol. 2010, 13 (4): 284-288.PubMedCentralCrossRefPubMed Padma MV, Bhasin A, Bhatia R, Garg A, Singh MB, Tripathi M, Prasad K: Normobaric oxygen therapy in acute ischemic stroke: a pilot study in Indian patients. Ann Indian Acad Neurol. 2010, 13 (4): 284-288.PubMedCentralCrossRefPubMed
9.
go back to reference Henninger N, Bratane BT, Bastan B, Bouley J, Fisher M: Normobaric hyperoxia and delayed tPA treatment in a rat embolic stroke model. J Cereb Blood Flow Metab. 2009, 29 (1): 119-129.CrossRefPubMed Henninger N, Bratane BT, Bastan B, Bouley J, Fisher M: Normobaric hyperoxia and delayed tPA treatment in a rat embolic stroke model. J Cereb Blood Flow Metab. 2009, 29 (1): 119-129.CrossRefPubMed
10.
11.
go back to reference Singhal AB, Dijkhuizen RM, Rosen BR, Lo EH: Normobaric hyperoxia reduces MRI diffusion abnormalities and infarct size in experimental stroke. Neurology. 2002, 58 (6): 945-952.CrossRefPubMed Singhal AB, Dijkhuizen RM, Rosen BR, Lo EH: Normobaric hyperoxia reduces MRI diffusion abnormalities and infarct size in experimental stroke. Neurology. 2002, 58 (6): 945-952.CrossRefPubMed
12.
go back to reference Liu S, Connor J, Peterson S, Shuttleworth CW, Liu KJ: Direct visualization of trapped erythrocytes in rat brain after focal ischemia and reperfusion. J Cereb Blood Flow Metab. 2002, 22 (10): 1222-1230.CrossRefPubMed Liu S, Connor J, Peterson S, Shuttleworth CW, Liu KJ: Direct visualization of trapped erythrocytes in rat brain after focal ischemia and reperfusion. J Cereb Blood Flow Metab. 2002, 22 (10): 1222-1230.CrossRefPubMed
13.
go back to reference Reffelmann T, Kloner RA: Microvascular alterations after temporary coronary artery occlusion: the no-reflow phenomenon. J Cardiovasc Pharmacol Ther. 2004, 9 (3): 163-172.CrossRefPubMed Reffelmann T, Kloner RA: Microvascular alterations after temporary coronary artery occlusion: the no-reflow phenomenon. J Cardiovasc Pharmacol Ther. 2004, 9 (3): 163-172.CrossRefPubMed
14.
go back to reference Liu S, Liu W, Ding W, Miyake M, Rosenberg GA, Liu KJ: Electron paramagnetic resonance-guided normobaric hyperoxia treatment protects the brain by maintaining penumbral oxygenation in a rat model of transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2006, 26 (10): 1274-1284.CrossRefPubMed Liu S, Liu W, Ding W, Miyake M, Rosenberg GA, Liu KJ: Electron paramagnetic resonance-guided normobaric hyperoxia treatment protects the brain by maintaining penumbral oxygenation in a rat model of transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2006, 26 (10): 1274-1284.CrossRefPubMed
15.
go back to reference Liu S, Shi H, Liu W, Furuichi T, Timmins GS, Liu KJ: Interstitial pO2 in ischemic penumbra and core are differentially affected following transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab. 2004, 24 (3): 343-349.CrossRefPubMed Liu S, Shi H, Liu W, Furuichi T, Timmins GS, Liu KJ: Interstitial pO2 in ischemic penumbra and core are differentially affected following transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab. 2004, 24 (3): 343-349.CrossRefPubMed
16.
go back to reference Komine-Kobayashi M, Chou N, Mochizuki H, Nakao A, Mizuno Y, Urabe T: Dual role of Fcgamma receptor in transient focal cerebral ischemia in mice. Stroke. 2004, 35 (4): 958-963.CrossRefPubMed Komine-Kobayashi M, Chou N, Mochizuki H, Nakao A, Mizuno Y, Urabe T: Dual role of Fcgamma receptor in transient focal cerebral ischemia in mice. Stroke. 2004, 35 (4): 958-963.CrossRefPubMed
17.
go back to reference Walder CE, Green SP, Darbonne WC, Mathias J, Rae J, Dinauer MC, Curnutte JT, Thomas GR: Ischemic stroke injury is reduced in mice lacking a functional NADPH oxidase. Stroke. 1997, 28 (11): 2252-2258.CrossRefPubMed Walder CE, Green SP, Darbonne WC, Mathias J, Rae J, Dinauer MC, Curnutte JT, Thomas GR: Ischemic stroke injury is reduced in mice lacking a functional NADPH oxidase. Stroke. 1997, 28 (11): 2252-2258.CrossRefPubMed
18.
go back to reference Zhang N, Komine-Kobayashi M, Tanaka R, Liu M, Mizuno Y, Urabe T: Edaravone reduces early accumulation of oxidative products and sequential inflammatory responses after transient focal ischemia in mice brain. Stroke. 2005, 36 (10): 2220-2225.CrossRefPubMed Zhang N, Komine-Kobayashi M, Tanaka R, Liu M, Mizuno Y, Urabe T: Edaravone reduces early accumulation of oxidative products and sequential inflammatory responses after transient focal ischemia in mice brain. Stroke. 2005, 36 (10): 2220-2225.CrossRefPubMed
19.
go back to reference Namura S, Zhu J, Fink K, Endres M, Srinivasan A, Tomaselli KJ, Yuan J, Moskowitz MA: Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J Neurosci. 1998, 18 (10): 3659-3668.PubMed Namura S, Zhu J, Fink K, Endres M, Srinivasan A, Tomaselli KJ, Yuan J, Moskowitz MA: Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J Neurosci. 1998, 18 (10): 3659-3668.PubMed
20.
go back to reference Flamm ES, Demopoulos HB, Seligman ML, Poser RG, Ransohoff J: Free radicals in cerebral ischemia. Stroke. 1978, 9 (5): 445-447.CrossRefPubMed Flamm ES, Demopoulos HB, Seligman ML, Poser RG, Ransohoff J: Free radicals in cerebral ischemia. Stroke. 1978, 9 (5): 445-447.CrossRefPubMed
21.
go back to reference Ulatowski JA, Kirsch JR, Traystman RJ: Hypoxic reperfusion after ischemia in swine does not improve acute brain recovery. Am J Physiol. 1994, 267 (5 Pt 2): H1880-H1887.PubMed Ulatowski JA, Kirsch JR, Traystman RJ: Hypoxic reperfusion after ischemia in swine does not improve acute brain recovery. Am J Physiol. 1994, 267 (5 Pt 2): H1880-H1887.PubMed
22.
go back to reference Angelos MG, Kutala VK, Torres CA, He G, Stoner JD, Mohammad M, Kuppusamy P: Hypoxic reperfusion of the ischemic heart and oxygen radical generation. Am J Physiol Heart Circ Physiol. 2006, 290 (1): H341-H347.CrossRefPubMed Angelos MG, Kutala VK, Torres CA, He G, Stoner JD, Mohammad M, Kuppusamy P: Hypoxic reperfusion of the ischemic heart and oxygen radical generation. Am J Physiol Heart Circ Physiol. 2006, 290 (1): H341-H347.CrossRefPubMed
23.
go back to reference Lei B, Popp S, Capuano-Waters C, Cottrell JE, Kass IS: Lidocaine attenuates apoptosis in the ischemic penumbra and reduces infarct size after transient focal cerebral ischemia in rats. Neuroscience. 2004, 125 (3): 691-701.CrossRefPubMed Lei B, Popp S, Capuano-Waters C, Cottrell JE, Kass IS: Lidocaine attenuates apoptosis in the ischemic penumbra and reduces infarct size after transient focal cerebral ischemia in rats. Neuroscience. 2004, 125 (3): 691-701.CrossRefPubMed
24.
go back to reference Yin D, Zhou C, Kusaka I, Calvert JW, Parent AD, Nanda A, Zhang JH: Inhibition of apoptosis by hyperbaric oxygen in a rat focal cerebral ischemic model. J Cereb Blood Flow Metab. 2003, 23 (7): 855-864.CrossRefPubMed Yin D, Zhou C, Kusaka I, Calvert JW, Parent AD, Nanda A, Zhang JH: Inhibition of apoptosis by hyperbaric oxygen in a rat focal cerebral ischemic model. J Cereb Blood Flow Metab. 2003, 23 (7): 855-864.CrossRefPubMed
25.
go back to reference Anderson DC, Zhou C, Kusaka I, Calvert JW, Parent AD, Nanda A, Zhang JH: A pilot study of hyperbaric oxygen in the treatment of human stroke. Stroke. 1991, 22 (9): 1137-1142.CrossRefPubMed Anderson DC, Zhou C, Kusaka I, Calvert JW, Parent AD, Nanda A, Zhang JH: A pilot study of hyperbaric oxygen in the treatment of human stroke. Stroke. 1991, 22 (9): 1137-1142.CrossRefPubMed
26.
go back to reference Lou M, Eschenfelder CC, Herdegen T, Brecht S, Deuschl G: Therapeutic window for use of hyperbaric oxygenation in focal transient ischemia in rats. Stroke. 2004, 35 (2): 578-583.CrossRefPubMed Lou M, Eschenfelder CC, Herdegen T, Brecht S, Deuschl G: Therapeutic window for use of hyperbaric oxygenation in focal transient ischemia in rats. Stroke. 2004, 35 (2): 578-583.CrossRefPubMed
27.
go back to reference Veltkamp R, Sun L, Herrmann O, Wolferts G, Hagmann S, Siebing DA, Marti HH, Veltkamp C, Schwaninger M: Oxygen therapy in permanent brain ischemia: potential and limitations. Brain Res. 2006, 1107 (1): 185-191.CrossRefPubMed Veltkamp R, Sun L, Herrmann O, Wolferts G, Hagmann S, Siebing DA, Marti HH, Veltkamp C, Schwaninger M: Oxygen therapy in permanent brain ischemia: potential and limitations. Brain Res. 2006, 1107 (1): 185-191.CrossRefPubMed
28.
go back to reference Beynon C, Sun L, Marti HH, Heiland S, Veltkamp R: Delayed hyperbaric oxygenation is more effective than early prolonged normobaric hyperoxia in experimental focal cerebral ischemia. Neurosci Lett. 2007, 425 (3): 141-145.CrossRefPubMed Beynon C, Sun L, Marti HH, Heiland S, Veltkamp R: Delayed hyperbaric oxygenation is more effective than early prolonged normobaric hyperoxia in experimental focal cerebral ischemia. Neurosci Lett. 2007, 425 (3): 141-145.CrossRefPubMed
29.
go back to reference Chan PH, Kawase M, Murakami K, Chen SF, Li Y, Calagui B, Reola L, Carlson E, Epstein CJ: Overexpression of SOD1 in transgenic rats protects vulnerable neurons against ischemic damage after global cerebral ischemia and reperfusion. J Neurosci. 1998, 18 (20): 8292-8299.PubMed Chan PH, Kawase M, Murakami K, Chen SF, Li Y, Calagui B, Reola L, Carlson E, Epstein CJ: Overexpression of SOD1 in transgenic rats protects vulnerable neurons against ischemic damage after global cerebral ischemia and reperfusion. J Neurosci. 1998, 18 (20): 8292-8299.PubMed
Metadata
Title
Extended normobaric hyperoxia therapy yields greater neuroprotection for focal transient ischemia-reperfusion in rats
Authors
Zhongrui Yuan
Rong Pan
Wenlan Liu
Ke Jian Liu
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Medical Gas Research / Issue 1/2014
Electronic ISSN: 2045-9912
DOI
https://doi.org/10.1186/2045-9912-4-14

Other articles of this Issue 1/2014

Medical Gas Research 1/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine