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The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury

BACKGROUND: The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI). METHODS: Anesthetized male Sprague–Dawley rats were divided into...

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Autores principales: Lu, Chung-Che, Nyam, Tee-Tau Eric, Kuo, Jinn-Rung, Lee, Yao-Lin, Chio, Chung-Ching, Wang, Che-Chuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228939/
https://www.ncbi.nlm.nih.gov/pubmed/34171999
http://dx.doi.org/10.1186/s12868-021-00649-w
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author Lu, Chung-Che
Nyam, Tee-Tau Eric
Kuo, Jinn-Rung
Lee, Yao-Lin
Chio, Chung-Ching
Wang, Che-Chuan
author_facet Lu, Chung-Che
Nyam, Tee-Tau Eric
Kuo, Jinn-Rung
Lee, Yao-Lin
Chio, Chung-Ching
Wang, Che-Chuan
author_sort Lu, Chung-Che
collection PubMed
description BACKGROUND: The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI). METHODS: Anesthetized male Sprague–Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-d-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI. RESULTS: The results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells. CONCLUSIONS: We concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI.
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spelling pubmed-82289392021-06-28 The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury Lu, Chung-Che Nyam, Tee-Tau Eric Kuo, Jinn-Rung Lee, Yao-Lin Chio, Chung-Ching Wang, Che-Chuan BMC Neurosci Research BACKGROUND: The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI). METHODS: Anesthetized male Sprague–Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-d-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI. RESULTS: The results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells. CONCLUSIONS: We concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI. BioMed Central 2021-06-25 /pmc/articles/PMC8228939/ /pubmed/34171999 http://dx.doi.org/10.1186/s12868-021-00649-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Lu, Chung-Che
Nyam, Tee-Tau Eric
Kuo, Jinn-Rung
Lee, Yao-Lin
Chio, Chung-Ching
Wang, Che-Chuan
The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury
title The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury
title_full The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury
title_fullStr The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury
title_full_unstemmed The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury
title_short The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury
title_sort neuroprotective effects of amn082 on neuronal apoptosis in rats after traumatic brain injury
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228939/
https://www.ncbi.nlm.nih.gov/pubmed/34171999
http://dx.doi.org/10.1186/s12868-021-00649-w
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