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Why the brain needs oxygen and gravity;
a (free) radical perspective!
Tak skal du have!
- Prof. Damian M. Bailey
Royal Society Wolfson Research Fellow
Why the brain needs oxygen and gravity; a (free) radical - - PowerPoint PPT Presentation
Why the brain needs oxygen and gravity; a (free) radical - - PowerPoint PPT Presentation
Why the brain needs oxygen and gravity; a (free) radical perspective! Tak skal du have! Prof. Damian M. Bailey Royal Society Wolfson Research Fellow Diolch i chi am wrando ar fy sgwrs heddiw! Neurovascular Research Laboratory Bill
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Lewis Fall Teresa Filiponni Danielle Hodson Chris Marley Julien Brugniaux Kevin Evans Dean Whitcombe
Neurovascular Research Laboratory
Bill George Tom Calverley Ben Stacey Tom Owens Trevor Harris Martin Steggall George Rose Angelo Ianetelli
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Masters PhD Post-doc
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Background reading
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Setting the scene
Evolution, O2 and Gravity
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Bailey DM et al. J Physiol 597:15-28, 2019
Coupled evolution of life and O2
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5 10 15 20 25 2000 2500 3000 3500 4000 4500
Atmospheric O2 (%) Time (Years)
5,340 m
But enjoy it while it lasts!
Bailey DM et al. J Physiol 597:15-28, 2019
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High energy demand
2% body mass 20% energy budget Bailey DM et al. High Alt Med Biol 18: 73-79, 2017
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Vulnerable to failure
PcO2 = 25 mmHg CMRO2 = 30 nmol/mL/s cO2 = 30 nmol/mL
Bailey DM et al. High Alt Med Biol 18: 73-79, 2017
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…and needs gravity
Bailey DM et al. J Physiol 2019 (in-the-press)
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An impressive defense system
Metabolic
Nerve activity
Autoregulatory
BP
Neurogenic
Cerebral SNA
Chemical
Tension PCO2 PO2 CBF CBF CBF CBF
Bailey DM et al. FASEB J 32: 2305-2314, 2018
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Setting the stimulus
How does the human brain sense O2 and gravity?
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Inflow Outflow
Laboratory
Net exchange (x/100g/min) = Blood flow x a-jvD
Bailey DM et al. Circulation 135: 166-176, 2017
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Clinical
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Comparative
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Himalayas Chile Peru
Applied
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Super-human!
11 m 54 s 24 m 03 s
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Fun!
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Setting the sense
How does the human brain sense O2 and gravity?
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Brief word on free radicals
Luca M. Bailey (2018). Nature (in preparation!) 6 years young
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Bailey DM. Ad Exp Med Biol 543: 201-221 , 2003
Techniques: EPR spectroscopy Ozone-based chemiluminescence
2 4 6 8 10 500 250
HbNO HbSNO+HbNO Output (mV) Time (s)
Bailey DM et al. Circulation 135:166-176, 2017
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Arterial Venous
Bailey DM et al. J Cereb Blood Flow Metab 31: 1020-1026, 2011 Bailey DM et al. Circulation 135:166-176, 2017
General findings
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Cerebral O2 delivery is well preserved
20 40 60 80 100
- 50
50 100 150
CBF CDO2 % of Apnea %∆CBF and CDO2
11:35 0:00
Bailey DM et al. FASEB J 32: 2305-2314, 2018 Bailey DM et al. Circulation 135:166-176, 2017
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Human evidence for cerebral O2-sensing?
0.5 1 1.5 2 2.5 3 3.5
Normoxia Hypoxia
CMRO2 (µmol/g/min)
Bailey DM et al. J Cereb Blood Flow Metab 31: 1020-1026, 2011 PmitO2 15 ± 4 PmitO2 1 ± 6 Bailey DM et al. Stroke (submitted)
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Nature’s Oxygen Olympics
Common Crucian Carp Sea turtle Canadian Bar Headed Goose
100,000 min Tastey and tough:
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Gravity
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B B B
↑Blood brain barrier permeability
Bailey DM et al. Exp Physiol 96: 1196-1207, 2011
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Bailey DM. et al. Am J Appl Physiol Heart Circ Physiol 298: H671-H678, 2010
Free radicals are good; not just simply bad or plain ugly
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Quantum-regulation of O2-sensing-”Physicsiology”
Quantum trigger
Bailey DM et al. Exp Physiol 104: 453-457, 2019
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Restoration of brain circulation and cellular functions hours post-mortem
Zvonimir Vrselja1,2,18, Stefano G. Daniele1,2,3,18, John Silbereis1,2, Francesca Talpo1,2,4, Yury M. Morozov1,2, André M. M. Sousa1,2, Brian S. Tanaka5,6,7, Mario Skarica1,2, Mihovil Pletikos1,2,8, Navjot Kaur1,2, Zhen W . Zhuang9, Zhao Liu9,10, Rafeed Alkawadri6,11, Albert J. Sinusas9,10, Stephen R. Latham12, Stephen G. Waxman5,6,7 & Nenad Sestan1,2,13,14,15,16,17*
S P S P Centrifugal pump Haemodiafjltration membrane Pulse generator Liquid chiller Ultrasound
a
Computer interface Brain chamber Brain venous return S Venous return pump Arterial
- xygenator
Gas source Perfusate reservoir bag Exchange solution Heat exchanger
b
Interventions
- Exp. conditions
1 h 2 h 3 h 4 h 5 h 6 h 7 h 8 h 9 h 10 h Rewarming period (25 to 37 °C) 1 h PMI 10 h PMI CP BEx Brain fush Brain perfusion Brain extraction and processing Brain processing AM Death Surgical preparation Brain fush Brain perfusion monitoring Start of perfusion Perfusate samplings Perfusate equilibration
c
Continuous Pulsatile BEx system Flow pattern Venous sample Arterial sample R-ICA L-ICA Venous return Direction
- f fow
Optional dural fold Dura with enclosed sagittal sinus Optional dura cut line PG Residual base of skull
- n system and experimental workflow. a, Simplified
the dura can be carefully cut and folded medially to
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Bailey DM et al. Nature R1
Brain death is a progressive (and potentially reversible!) process
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“Iceberg of Ignorance”
O2-sensing
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But I hope this has given you some fun ideas to explore!
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Lots of ideas…
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2
Needs gravity!
1
Needs O2!
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Never a lone journey
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Niels Secher, Bente Pedersen, Kirsten Möller
University of Copenhagen, Denmark
Joe McCord
University of Colorado, USA
Peter Raven
University of North Texas, USA
Sylvia Pietri and Marcel Culcasi
University of Marseilles, France
Peter Bärtsch
University of Heidelberg, Germany
Philip Ainslie, Anthony Bain, Shigehiko Ogoh
University of British Columbia, Canada Toyo University, Japan
Collaborators and funding
Patrice Brassard, Sam Lucas, Jim Cotter
University of Laval, Quebec University of Birmingham, UK University of Otago, New Zealand
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Tak for at lytte!