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Translational Stroke Research
Published in: Translational Stroke Research 4/2019

01-08-2019 | Original Article

Low Oxygen Post Conditioning as an Efficient Non-pharmacological Strategy to Promote Motor Function After Stroke

Authors: Giovanni Pietrogrande, Katarzyna Zalewska, Zidan Zhao, Sarah J. Johnson, Michael Nilsson, Frederick R. Walker

Published in: Translational Stroke Research | Issue 4/2019

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Abstract

Low oxygen post conditioning (LOPC) has shown promising results in terms of neuroprotection after stroke, but the effects on motor function have not been considered. Cortical stroke targeting the motor and sensory cortex was induced by photothrombotic occlusion and after 48 h allocated to LOPC (11% O2) for 2 weeks. Motor impairment was assessed using the cylinder and grid walk tests during the exposure period and for two further weeks upon completion of the intervention. Neuroprotection was evaluated by histological and molecular analysis at two time points. Two weeks of LOPC was sufficient to significantly reduce motor deficits and tissue loss after stroke. This functional improvement was associated with increased capillary density, enhanced levels of BDNF, decreased neuronal loss and decreased microglia activation. These improvements, in most instances, were maintained up to 2 weeks after the end of the treatment. To our knowledge, this is the first study to demonstrate that LOPC induces a persistent improvement in motor function and neuroprotection after stroke, and in doing so provides evidence to support a case for considering taking LOPC forward to early stage clinical research.
Literature
1.
Brugniaux JV, Schmitt L, Robach P, Nicolet G, Fouillot JP, Moutereau S, et al. Eighteen days of “living high, training low” stimulate erythropoiesis and enhance aerobic performance in elite middle-distance runners. J Appl Physiol (1985). 2006;100(1):203–11.CrossRef
2.
Wehrlin JP, Zuest P, Hallén J, Marti B. Live high-train low for 24 days increases hemoglobin mass and red cell volume in elite endurance athletes. J Appl Physiol (1985). 2006;100(6):1938–45.CrossRef
3.
Rodriguez FA, et al. Performance of runners and swimmers after four weeks of intermittent hypobaric hypoxic exposure plus sea level training. J Appl Physiol (1985). 2007;103(5):1523–35.CrossRef
4.
Faiss R, Girard O, Millet GP. Advancing hypoxic training in team sports: from intermittent hypoxic training to repeated sprint training in hypoxia. Br J Sports Med. 2013;47(Suppl 1):i45–50.CrossRefPubMed
5.
Nakada Y, Canseco DC, Thet SW, Abdisalaam S, Asaithamby A, Santos CX, et al. Hypoxia induces heart regeneration in adult mice. Nature. 2017;541(7636):222–7.CrossRefPubMed
6.
Zhu LL, Zhao T, Li HS, Zhao H, Wu LY, Ding AS, et al. Neurogenesis in the adult rat brain after intermittent hypoxia. Brain Res. 2005;1055(1–2):1–6.CrossRefPubMed
7.
Tsai YW, Yang YR, Sun SH, Liang KC, Wang RY. Post ischemia intermittent hypoxia induces hippocampal neurogenesis and synaptic alterations and alleviates long-term memory impairment. J Cereb Blood Flow Metab. 2013;33(5):764–73.CrossRefPubMedPubMedCentral
8.
Tsai YW, Yang YR, Wang PS, Wang RY. Intermittent hypoxia after transient focal ischemia induces hippocampal neurogenesis and c-Fos expression and reverses spatial memory deficits in rats. PLoS One. 2011;6(8):e24001.CrossRefPubMedPubMedCentral
9.
Qiao Y, Liu Z, Yan X, Luo C. Effect of intermittent hypoxia on neuro-functional recovery post brain ischemia in mice. J Mol Neurosci. 2015;55(4):923–30.CrossRefPubMed
10.
Leconte C, Tixier E, Freret T, Toutain J, Saulnier R, Boulouard M, et al. Delayed hypoxic postconditioning protects against cerebral ischemia in the mouse. Stroke. 2009;40(10):3349–55.CrossRefPubMed
11.
Astorino TA, Harness ET, White AC. Efficacy of acute intermittent hypoxia on physical function and health status in humans with spinal cord injury: a brief review. Neural Plast. 2015;2015:409625.CrossRefPubMedPubMedCentral
12.
Dale EA, Ben Mabrouk F, Mitchell GS. Unexpected benefits of intermittent hypoxia: enhanced respiratory and nonrespiratory motor function. Physiology (Bethesda). 2014;29(1):39–48.
13.
Baillieul S, Chacaroun S, Doutreleau S, Detante O, Pépin JL, Verges S. Hypoxic conditioning and the central nervous system: a new therapeutic opportunity for brain and spinal cord injuries? Exp Biol Med (Maywood). 2017;242(11):1198–206.CrossRef
14.
Trumbower RD, Jayaraman A, Mitchell GS, Rymer WZ. Exposure to acute intermittent hypoxia augments somatic motor function in humans with incomplete spinal cord injury. Neurorehabil Neural Repair. 2012;26(2):163–72.CrossRefPubMed
15.
Hayes HB, Jayaraman A, Herrmann M, Mitchell GS, Rymer WZ, Trumbower RD. Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Neurology. 2014;82(2):104–13.CrossRefPubMedPubMedCentral
16.
Navarrete-Opazo A, Alcayaga J, Sepúlveda O, Rojas E, Astudillo C. Repetitive intermittent hypoxia and locomotor training enhances walking function in incomplete spinal cord injury subjects: a randomized, triple-blind, placebo-controlled clinical trial. J Neurotrauma. 2017;34(9):1803–12.CrossRefPubMed
17.
Trumbower RD, Hayes HB, Mitchell GS, Wolf SL, Stahl VA. Effects of acute intermittent hypoxia on hand use after spinal cord trauma: a preliminary study. Neurology. 2017;89(18):1904–7.CrossRefPubMedPubMedCentral
18.
19.
20.
Zalewska K, Pietrogrande G, Ong LK, Abdolhoseini M, Kluge M, Johnson SJ, et al. Sustained administration of corticosterone at stress-like levels after stroke suppressed glial reactivity at sites of thalamic secondary neurodegeneration. Brain Behav Immun. 2018;69:210–22.
21.
Zalewska K, Ong LK, Johnson SJ, Nilsson M, Walker FR. Oral administration of corticosterone at stress-like levels drives microglial but not vascular disturbances post-stroke. Neuroscience. 2017;352:30–8.CrossRefPubMed
22.
Pietrogrande G, Mabotuwana N, Zhao Z, Abdolhoseini M, Johnson SJ, Nilsson M, et al. Chronic stress induced disturbances in Laminin: A significant contributor to modulating microglial pro-inflammatory tone? Brain Behav Immun. 2018;68:23–3.
23.
Zhao Z, Ong LK, Johnson S, Nilsson M, Walker FR. Chronic stress induced disruption of the peri-infarct neurovascular unit following experimentally induced photothrombotic stroke. J Cereb Blood Flow Metab. 2017;37(12):3709–24.CrossRefPubMedPubMedCentral
24.
Paxinos G, Franklin KBJ, editors. The mouse brain in stereotaxic coordinates. Compact. 2nd ed. Amsterdam: Elsevier Academic Press; 2004.
25.
Joo SP, Xie W, Xiong X, Xu B, Zhao H. Ischemic postconditioning protects against focal cerebral ischemia by inhibiting brain inflammation while attenuating peripheral lymphopenia in mice. Neuroscience. 2013;243:149–57.CrossRefPubMed
26.
Schabitz WR, Steigleder T, Cooper-Kuhn CM, Schwab S, Sommer C, Schneider A, et al. Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis. Stroke. 2007;38(7):2165–72.CrossRefPubMed
27.
Ploughman M, Windle V, MacLellan CL, White N, Dore JJ, Corbett D. Brain-derived neurotrophic factor contributes to recovery of skilled reaching after focal ischemia in rats. Stroke. 2009;40(4):1490–5.CrossRefPubMed
28.
Stanne TM, et al. Low circulating acute brain-derived neurotrophic factor levels are associated with poor long-term functional outcome after ischemic stroke. Stroke. 2016;47(7):1943–5.CrossRefPubMed
29.
30.
Li Y, Lu Z, Keogh CL, Yu SP, Wei L. Erythropoietin-induced neurovascular protection, angiogenesis, and cerebral blood flow restoration after focal ischemia in mice. J Cereb Blood Flow Metab. 2007;27(5):1043–54.CrossRefPubMed
31.
Harb R, Whiteus C, Freitas C, Grutzendler J. In vivo imaging of cerebral microvascular plasticity from birth to death. J Cereb Blood Flow Metab. 2013;33(1):146–56.CrossRefPubMed
32.
Zhang L, Zhang ZG, Zhang RL, Lu M, Krams M, Chopp M. Effects of a selective CD11b/CD18 antagonist and recombinant human tissue plasminogen activator treatment alone and in combination in a rat embolic model of stroke. Stroke. 2003;34(7):1790–5.CrossRefPubMed
33.
Prestigiacomo CJ, Kim SC, Connolly ES, Liao H, Yan SF, Pinsky DJ, et al. CD18-mediated neutrophil recruitment contributes to the pathogenesis of reperfused but not nonreperfused stroke. Stroke. 1999;30(5):1110–7.CrossRefPubMed
34.
35.
36.
Zhu XH, Yan HC, Zhang J, Qu HD, Qiu XS, Chen L, et al. Intermittent hypoxia promotes hippocampal neurogenesis and produces antidepressant-like effects in adult rats. J Neurosci. 2010;30(38):12653–63.CrossRefPubMedPubMedCentral
37.
Kushwah N, Jain V, Deep S, Prasad D, Singh SB, Khan N. Neuroprotective role of intermittent hypobaric hypoxia in unpredictable chronic mild stress induced depression in rats. PLoS One. 2016;11(2):e0149309.CrossRefPubMedPubMedCentral
38.
Jones KA, Zouikr I, Patience M, Clarkson AN, Isgaard J, Johnson SJ, et al. Chronic stress exacerbates neuronal loss associated with secondary neurodegeneration and suppresses microglial-like cells following focal motor cortex ischemia in the mouse. Brain Behav Immun. 2015;48:57–67.CrossRefPubMed
39.
Walker FR, Jones KA, Patience MJ, Zhao Z, Nilsson M. Stress as necessary component of realistic recovery in animal models of experimental stroke. J Cereb Blood Flow Metab. 2014;34(2):208–14.CrossRefPubMed
Metadata
Title
Low Oxygen Post Conditioning as an Efficient Non-pharmacological Strategy to Promote Motor Function After Stroke
Authors
Giovanni Pietrogrande
Katarzyna Zalewska
Zidan Zhao
Sarah J. Johnson
Michael Nilsson
Frederick R. Walker
Publication date
01-08-2019
Publisher
Springer US
Published in
Translational Stroke Research / Issue 4/2019
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-018-0656-5

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