Low Oxygen Post Conditioning as an Efficient Non-pharmacological Strategy to Promote Motor Function After Stroke
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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.
KeywordsStroke Motor function Neuroprotection BDNF Hypoxia Angiogenesis Inflammation
Experiments were designed by GP, MN and FRW and performed by GP, KZ and ZZ. Manuscript was written by GP and FRW and edited by GP, SJ, MN and FRW.
This study was supported by the Hunter Medical Research Institute, Faculty of Health and Medicine Pilot Grant and The University of Newcastle, Australia.
Compliance with Ethical Standards
All experiments were conducted in accordance with the New South Wales Animals Research Act (1985) and the Australian Code of Practice for the use of animals for scientific purposes.
Conflict of Interest
The authors declare that they have no conflicts of interest.
All experiments were approved by the University of Newcastle Animal Care and Ethics Committee.
- 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.Google Scholar
- 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.CrossRefGoogle Scholar
- 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.Google Scholar
- 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.Google Scholar
- 24.Paxinos G, Franklin KBJ, editors. The mouse brain in stereotaxic coordinates. Compact. 2nd ed. Amsterdam: Elsevier Academic Press; 2004.Google Scholar
- 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.CrossRefGoogle Scholar