L-Carnitine and extendin-4 improve outcomes following moderate brain contusion injury

Chen, H; Chan, YL; Linnane, C; Mao, Y; Anwer, AG; Sapkota, A; Annissa, TF; Herok, G; Vissel, B; Oliver, BG; Saad, S; Gorrie, CA

L-Carnitine and extendin-4 improve outcomes following moderate brain contusion injury

Chen, H

Chan, YL

Linnane, C Mao, Y Anwer, AG Sapkota, A Annissa, TF Herok, G Vissel, B

Oliver, BG

Saad, S

Gorrie, CA

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Publication Type:: Journal Article
Citation:: Scientific Reports, 2018, 8 (1)
Issue Date:: 2018-12-01

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Field	Value	Language
dc.contributor.author	Chen, H https://orcid.org/0000-0001-6883-3752	en_US
dc.contributor.author	Chan, YL https://orcid.org/0000-0002-9605-4200	en_US
dc.contributor.author	Linnane, C	en_US
dc.contributor.author	Mao, Y	en_US
dc.contributor.author	Anwer, AG	en_US
dc.contributor.author	Sapkota, A	en_US
dc.contributor.author	Annissa, TF	en_US
dc.contributor.author	Herok, G	en_US
dc.contributor.author	Vissel, B https://orcid.org/0000-0001-8860-8050	en_US
dc.contributor.author	Oliver, BG https://orcid.org/0000-0002-7122-9262	en_US
dc.contributor.author	Saad, S https://orcid.org/0000-0001-8067-8046	en_US
dc.contributor.author	Gorrie, CA https://orcid.org/0000-0001-5934-2492	en_US
dc.date.available	2018-06-21	en_US
dc.date.issued	2018-12-01	en_US
dc.identifier.citation	Scientific Reports, 2018, 8 (1)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/126551
dc.description.abstract	© 2018, The Author(s). There is a need for pharmaceutical agents that can reduce neuronal loss and improve functional deficits following traumatic brain injury (TBI). Previous research suggests that oxidative stress and mitochondrial dysfunction play a major role in neuronal damage after TBI. Therefore, this study aimed to investigate two drugs known to have antioxidant effects, L-carnitine and exendin-4, in rats with moderate contusive TBI. L-carnitine (1.5 mM in drinking water) or exendin-4 (15 µg/kg/day, ip) were given immediately after the injury for 2 weeks. Neurological function and brain histology were examined (24 h and 6 weeks post injury). The rats with TBI showed slight sensory, motor and memory functional deficits at 24 h, but recovered by 6 weeks. Both treatments improved sensory and motor functions at 24 h, while only exendin-4 improved memory. Both treatments reduced cortical contusion at 24 h and 6 weeks, however neither affected gliosis and inflammatory cell activation. Oxidative stress was alleviated and mitochondrial reactive oxygen species was reduced by both treatments, however only mitochondrial functional marker protein transporter translocase of outer membrane 20 was increased at 24 h post injury. In conclusion, L-carnitine and exendin-4 treatments immediately after TBI can improve neurological functional outcome and tissue integrity by reducing oxidative stress.	en_US
dc.relation.ispartof	Scientific Reports	en_US
dc.relation.isbasedon	10.1038/s41598-018-29430-6	en_US
dc.subject.mesh	Brain	en_US
dc.subject.mesh	Neurons	en_US
dc.subject.mesh	Mitochondria	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Rats	en_US
dc.subject.mesh	Rats, Sprague-Dawley	en_US
dc.subject.mesh	Disease Models, Animal	en_US
dc.subject.mesh	Reactive Oxygen Species	en_US
dc.subject.mesh	Carnitine	en_US
dc.subject.mesh	Antioxidants	en_US
dc.subject.mesh	Oxidative Stress	en_US
dc.subject.mesh	Brain Injuries, Traumatic	en_US
dc.subject.mesh	Brain Contusion	en_US
dc.subject.mesh	Exenatide	en_US
dc.title	L-Carnitine and extendin-4 improve outcomes following moderate brain contusion injury	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	8	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
utslib.for	1109 Neurosciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/DVC (Teaching and Learning)
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.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	8	en_US

Abstract:

© 2018, The Author(s). There is a need for pharmaceutical agents that can reduce neuronal loss and improve functional deficits following traumatic brain injury (TBI). Previous research suggests that oxidative stress and mitochondrial dysfunction play a major role in neuronal damage after TBI. Therefore, this study aimed to investigate two drugs known to have antioxidant effects, L-carnitine and exendin-4, in rats with moderate contusive TBI. L-carnitine (1.5 mM in drinking water) or exendin-4 (15 µg/kg/day, ip) were given immediately after the injury for 2 weeks. Neurological function and brain histology were examined (24 h and 6 weeks post injury). The rats with TBI showed slight sensory, motor and memory functional deficits at 24 h, but recovered by 6 weeks. Both treatments improved sensory and motor functions at 24 h, while only exendin-4 improved memory. Both treatments reduced cortical contusion at 24 h and 6 weeks, however neither affected gliosis and inflammatory cell activation. Oxidative stress was alleviated and mitochondrial reactive oxygen species was reduced by both treatments, however only mitochondrial functional marker protein transporter translocase of outer membrane 20 was increased at 24 h post injury. In conclusion, L-carnitine and exendin-4 treatments immediately after TBI can improve neurological functional outcome and tissue integrity by reducing oxidative stress.

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http://hdl.handle.net/10453/126551