Nitroxides affect neurological deficits and lesion size induced by a rat model of traumatic brain injury

Zakarya, R; Sapkota, A; Chan, YL; Shah, J; Saad, S; Bottle, SE; Oliver, BG; Gorrie, CA; Chen, H

Nitroxides affect neurological deficits and lesion size induced by a rat model of traumatic brain injury

Zakarya, R

Sapkota, A Chan, YL

Shah, J Saad, S Bottle, SE Oliver, BG

Gorrie, CA

Chen, H

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Publication Type:: Journal Article
Citation:: Nitric Oxide - Biology and Chemistry, 2020, 97 pp. 57 - 65
Issue Date:: 2020-04-01

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Field	Value	Language
dc.contributor.author	Zakarya, R https://orcid.org/0000-0002-9259-9369	en_US
dc.contributor.author	Sapkota, A	en_US
dc.contributor.author	Chan, YL https://orcid.org/0000-0002-9605-4200	en_US
dc.contributor.author	Shah, J	en_US
dc.contributor.author	Saad, S	en_US
dc.contributor.author	Bottle, SE	en_US
dc.contributor.author	Oliver, BG https://orcid.org/0000-0002-7122-9262	en_US
dc.contributor.author	Gorrie, CA https://orcid.org/0000-0001-5934-2492	en_US
dc.contributor.author	Chen, H https://orcid.org/0000-0001-6883-3752	en_US
dc.date.available	2021-02-13T18:05:17Z
dc.date.issued	2020-04-01	en_US
dc.identifier.citation	Nitric Oxide - Biology and Chemistry, 2020, 97 pp. 57 - 65	en_US
dc.identifier.issn	1089-8603	en_US
dc.identifier.uri	http://hdl.handle.net/10453/138727
dc.description.abstract	© 2020 Elsevier Inc. Research has attributed tissue damage post-traumatic brain injury (TBI) to two-pronged effects, increased reactive oxygen species (ROS) and impairment of endogenous antioxidant defence systems, underpinned by manganese superoxide dismutase (MnSOD). Novel antioxidant nitroxides have been shown to mimic MnSOD to ameliorate oxidative stress related disorders. This study aimed to investigate the effects of two nitroxides, CTMIO and DCTEIO, on the neurological outcomes following moderate TBI in rats induced by a weight drop device. The rats were immediately treated with CTMIO and DCTEIO (40 mM in drinking water) post-injury for up to 2 weeks. The brains were histologically examined at 24 h and 6 weeks post injury. DCTEIO reduced the lesion size at both 24h and 6 weeks, with normalised performance in sensory, motor and cognitive tests at 24h post-injury. Astrogliosis was heightened by DCTEIO at 24h and still elevated at 6 weeks in this group. In TBI brains, cellular damage was evident as reflected by changes in markers of mitophagy and autophagy (increased fission marker dynamin-related protein (Drp)-1, and autophagy marker light chain 3 (LC3)A/B and reduced fusion marker optic atrophy (Opa)-1). These were normalised by DCTEIO treatment. CTMIO, on the other hand, seems to be toxic to the injured brains, by increasing injury size at 6 weeks. In conclusion, DCTEIO significantly improved tissue repair and preserved neurological function in rats with TBI possibly via a mitophagy mechanism. This study provides evidence for DCTEIO as a promising new option to alleviate lesion severity after moderate TBI, which is not actively treated.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1026880
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1158186
dc.relation	http://purl.org/au-research/grants/nhmrc/1026880
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1159211
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1158186
dc.relation.ispartof	Nitric Oxide - Biology and Chemistry	en_US
dc.relation.isbasedon	10.1016/j.niox.2020.02.001	en_US
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.title	Nitroxides affect neurological deficits and lesion size induced by a rat model of traumatic brain injury	en_US
dc.type	Journal Article
utslib.citation.volume	97	en_US
utslib.for	03 Chemical Sciences	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access	*
pubs.publication-status	Accepted	en_US
pubs.volume	97	en_US

Abstract:

© 2020 Elsevier Inc. Research has attributed tissue damage post-traumatic brain injury (TBI) to two-pronged effects, increased reactive oxygen species (ROS) and impairment of endogenous antioxidant defence systems, underpinned by manganese superoxide dismutase (MnSOD). Novel antioxidant nitroxides have been shown to mimic MnSOD to ameliorate oxidative stress related disorders. This study aimed to investigate the effects of two nitroxides, CTMIO and DCTEIO, on the neurological outcomes following moderate TBI in rats induced by a weight drop device. The rats were immediately treated with CTMIO and DCTEIO (40 mM in drinking water) post-injury for up to 2 weeks. The brains were histologically examined at 24 h and 6 weeks post injury. DCTEIO reduced the lesion size at both 24h and 6 weeks, with normalised performance in sensory, motor and cognitive tests at 24h post-injury. Astrogliosis was heightened by DCTEIO at 24h and still elevated at 6 weeks in this group. In TBI brains, cellular damage was evident as reflected by changes in markers of mitophagy and autophagy (increased fission marker dynamin-related protein (Drp)-1, and autophagy marker light chain 3 (LC3)A/B and reduced fusion marker optic atrophy (Opa)-1). These were normalised by DCTEIO treatment. CTMIO, on the other hand, seems to be toxic to the injured brains, by increasing injury size at 6 weeks. In conclusion, DCTEIO significantly improved tissue repair and preserved neurological function in rats with TBI possibly via a mitophagy mechanism. This study provides evidence for DCTEIO as a promising new option to alleviate lesion severity after moderate TBI, which is not actively treated.

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http://hdl.handle.net/10453/138727