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 George Tom Owens George Rose Martin Steggall Tom Calverley Ben Stacey Trevor Harris Dean Whitcombe Kevin Evans Julien Brugniaux Angelo Ianetelli Chris Marley Lewis Danielle Fall Teresa Hodson Filiponni

Masters PhD Post-doc

Background reading

Setting the scene Evolution, O 2 and Gravity

Coupled evolution of life and O 2 Bailey DM et al. J Physiol 597:15-28, 2019

But enjoy it while it lasts! 25 20 Atmospheric O 2 (%) 15 5,340 m 10 5 0 2000 2500 3000 3500 4000 4500 Time (Years) Bailey DM et al. J Physiol 597:15-28, 2019

High energy demand 2% body mass 20% energy budget Bailey DM et al. High Alt Med Biol 18: 73-79, 2017

Vulnerable to failure P c O 2 = 25 mmHg c O 2 = 30 nmol/mL CMRO 2 = 30 nmol/mL/s Bailey DM et al. High Alt Med Biol 18: 73-79, 2017

…and needs gravity Bailey DM et al. J Physiol 2019 (in-the-press)

An impressive defense system Metabolic CBF Nerve activity Autoregulatory CBF BP Neurogenic CBF Cerebral SNA Chemical PCO 2 CBF PO 2 Tension Bailey DM et al. FASEB J 32: 2305-2314, 2018

Setting the stimulus How does the human brain sense O 2 and gravity?

Laboratory Inflow Outflow Net exchange ( x /100g/min) = Blood flow x a-jv D Bailey DM et al. Circulation 135: 166-176, 2017

Clinical

Comparative

Applied Himalayas Chile Peru

Super-human! 11 m 54 s 24 m 03 s

Fun!

Setting the sense How does the human brain sense O 2 and gravity?

Brief word on free radicals 6 years young Luca M. Bailey (2018). Nature (in preparation!)

Techniques: EPR spectroscopy Bailey DM . Ad Exp Med Biol 543: 201-221 , 2003 Ozone-based chemiluminescence HbSNO+HbNO 10 Output (mV) 8 HbNO 6 4 2 0 0 250 500 Time (s) Bailey DM et al. Circulation 135:166-176, 2017

General findings Arterial Venous Bailey DM et al. Circulation 135:166-176, 2017 Bailey DM et al. J Cereb Blood Flow Metab 31: 1020-1026, 2011

Cerebral O 2 delivery is well preserved Bailey DM et al. Circulation 135:166-176, 2017 150 CBF % ∆ CBF and CDO 2 CDO 2 100 50 0 -50 0 20 40 60 80 100 0:00 11:35 % of Apnea Bailey DM et al. FASEB J 32: 2305-2314, 2018

Human evidence for cerebral O 2 -sensing? 3.5 3 ( µ mol/g/min) 2.5 CMRO 2 2 P mitO 2 P mitO 2 15 ± 4 1 ± 6 1.5 1 0.5 0 Normoxia Hypoxia Bailey DM et al. J Cereb Blood Flow Metab 31: 1020-1026, 2011 Bailey DM et al. Stroke (submitted)

Nature’s Oxygen Olympics Tastey and tough: 100,000 min Common Crucian Carp Sea turtle Canadian Bar Headed Goose

Gravity

↑Blood brain barrier permeability B B B Bailey DM et al . Exp Physiol 96: 1196-1207, 2011

Free radicals are good; not just simply bad or plain ugly Bailey DM . et al . Am J Appl Physiol Heart Circ Physiol 298: H671-H678, 2010

Quantum-regulation of O 2 -sensing-”Physicsiology” Quantum trigger Bailey DM et al. Exp Physiol 104: 453-457, 2019

Restoration of brain circulation and cellular functions hours post-mortem Zvonimir Vrselja 1,2,18 , Stefano G. Daniele 1,2,3,18 , John Silbereis 1,2 , Francesca Talpo 1,2,4 , Yury M. Morozov 1,2 , André M. M. Sousa 1,2 , Brian S. Tanaka 5,6,7 , Mario Skarica 1,2 , Mihovil Pletikos 1,2,8 , Navjot Kaur 1,2 , Zhen W . Zhuang 9 , Zhao Liu 9,10 , Rafeed Alkawadri 6,11 , Albert J. Sinusas 9,10 , Stephen R. Latham 12 , Stephen G. Waxman 5,6,7 & Nenad Sestan 1,2,13,14,15,16,17 * a b Dura with enclosed sagittal sinus Venous Computer interface Direction sample Optional dural Ultrasound Arterial Gas pattern Continuous of f ow Pulsatile fold Flow oxygenator source Brain PG chamber system S S B Ex L-ICA Residual S base of skull P Pulse Haemodia fj ltration membrane Optional dura Venous return R-ICA generator cut line Venous return pump Arterial sample c Start of perfusion Perfusate samplings Brain Interventions Perfusate equilibration venous return Perfusate P Exchange Surgical preparation reservoir bag solution Liquid chiller Brain f ush Heat Death exchanger Brain perfusion monitoring AM 1 h 2 h 3 h 4 h 5 h 6 h 7 h 8 h 9 h 10 h Rewarming period Brain Exp. conditions (25 to 37 °C) f ush Brain extraction Brain processing and processing 1 h PMI Centrifugal pump 10 h PMI CP Brain perfusion B Ex on system and experimental workflow. a , Simplified the dura can be carefully cut and folded medially to

Brain death is a progressive (and potentially reversible!) process Bailey DM et al. Nature R1

“Iceberg of Ignorance” O 2 -sensing

But I hope this has given you some fun ideas to explore!

Lots of ideas…

1 2 Needs O 2 ! Needs gravity!

Never a lone journey

Collaborators and funding Niels Secher, Bente Pedersen, Kirsten Möller University of Copenhagen, Denmark Peter Raven University of North Texas, USA Joe McCord University of Colorado, 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 Patrice Brassard, Sam Lucas, Jim Cotter University of Laval, Quebec University of Birmingham, UK University of Otago, New Zealand

Tak for at lytte!