Agmatine inhibits nuclear factor-κB nuclear translocation in acute spinal cord compression injury rat model

Secondary damage after acute spinal cord compression injury (SCCI) exacerbates initial insult. Nuclear factor kappa-B (NF-κB)-p65 activation is involved in SCCI deleterious effects. Agmatine (Agm) showed neuroprotection against various CNS injuries. However, Agm impact on NF-κB signaling in acute SC...

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Main Authors: Doaa M. Samy, Passainte S. Hassan, Cherine A. Ismail, Mona A. Hady, Mohamed A. Eshra
Format: Article
Language:English
Published: Taylor & Francis Group 2016-09-01
Series:Alexandria Journal of Medicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2090506815000706
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author Doaa M. Samy
Passainte S. Hassan
Cherine A. Ismail
Mona A. Hady
Mohamed A. Eshra
author_facet Doaa M. Samy
Passainte S. Hassan
Cherine A. Ismail
Mona A. Hady
Mohamed A. Eshra
author_sort Doaa M. Samy
collection DOAJ
description Secondary damage after acute spinal cord compression injury (SCCI) exacerbates initial insult. Nuclear factor kappa-B (NF-κB)-p65 activation is involved in SCCI deleterious effects. Agmatine (Agm) showed neuroprotection against various CNS injuries. However, Agm impact on NF-κB signaling in acute SCCI remains to be investigated. The present study compared the effectiveness of Agm therapy and decompression laminectomy (DL) in functional recovery, oxidative stress, inflammatory and apoptotic responses, and modulation of NF-κB activation in acute SCCI rat model. Rats were either sham-operated or subjected to SCCI at T8–9, using 2-Fr. catheter. SCCI rats were randomly treated with DL at T8–9, intraperitoneal Agm (100 mg/kg/day), combined (DL/Agm) treatment or saline (n = 16/group). After 28-days of neurological follow-up, spinal cords were either subjected to biochemical measurement of oxidative stress and inflammatory markers or histopathology and immuno-histochemistry for NF-κB-p65 and caspase-3 expression (n = 8/group). Agm was comparable to DL in facilitating neurological functions recovery, reducing inflammation (TNF-α/interleukin-6), and apoptosis. Agm was distinctive in combating oxidative stress. Agm neuroprotective effects were paralleled with inhibition of NF-κB-p65 nuclear translocation. Combined pharmacological and surgical interventions were proved superior in functional recovery. In conclusion, present research suggested a new mechanism for Agm neuroprotection in rats SCCI through inhibition of NF-κB activation.
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spelling doaj.art-6ac4b973b852473ebb47843c51a592a82022-12-21T21:59:31ZengTaylor & Francis GroupAlexandria Journal of Medicine2090-50682016-09-0152325126010.1016/j.ajme.2015.09.001Agmatine inhibits nuclear factor-κB nuclear translocation in acute spinal cord compression injury rat modelDoaa M. Samy0Passainte S. Hassan1Cherine A. Ismail2Mona A. Hady3Mohamed A. Eshra4Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, EgyptDepartment of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, EgyptDepartment of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, EgyptDepartment of Pathology, Faculty of Medicine, Alexandria University, Alexandria, EgyptDepartment of Neurosurgery, Faculty of Medicine, Alexandria Main University Hospital, Alexandria, EgyptSecondary damage after acute spinal cord compression injury (SCCI) exacerbates initial insult. Nuclear factor kappa-B (NF-κB)-p65 activation is involved in SCCI deleterious effects. Agmatine (Agm) showed neuroprotection against various CNS injuries. However, Agm impact on NF-κB signaling in acute SCCI remains to be investigated. The present study compared the effectiveness of Agm therapy and decompression laminectomy (DL) in functional recovery, oxidative stress, inflammatory and apoptotic responses, and modulation of NF-κB activation in acute SCCI rat model. Rats were either sham-operated or subjected to SCCI at T8–9, using 2-Fr. catheter. SCCI rats were randomly treated with DL at T8–9, intraperitoneal Agm (100 mg/kg/day), combined (DL/Agm) treatment or saline (n = 16/group). After 28-days of neurological follow-up, spinal cords were either subjected to biochemical measurement of oxidative stress and inflammatory markers or histopathology and immuno-histochemistry for NF-κB-p65 and caspase-3 expression (n = 8/group). Agm was comparable to DL in facilitating neurological functions recovery, reducing inflammation (TNF-α/interleukin-6), and apoptosis. Agm was distinctive in combating oxidative stress. Agm neuroprotective effects were paralleled with inhibition of NF-κB-p65 nuclear translocation. Combined pharmacological and surgical interventions were proved superior in functional recovery. In conclusion, present research suggested a new mechanism for Agm neuroprotection in rats SCCI through inhibition of NF-κB activation.http://www.sciencedirect.com/science/article/pii/S2090506815000706Spinal cord injuryAgmatineNuclear factor kappa BOxidative stressInflammationApoptosis
spellingShingle Doaa M. Samy
Passainte S. Hassan
Cherine A. Ismail
Mona A. Hady
Mohamed A. Eshra
Agmatine inhibits nuclear factor-κB nuclear translocation in acute spinal cord compression injury rat model
Alexandria Journal of Medicine
Spinal cord injury
Agmatine
Nuclear factor kappa B
Oxidative stress
Inflammation
Apoptosis
title Agmatine inhibits nuclear factor-κB nuclear translocation in acute spinal cord compression injury rat model
title_full Agmatine inhibits nuclear factor-κB nuclear translocation in acute spinal cord compression injury rat model
title_fullStr Agmatine inhibits nuclear factor-κB nuclear translocation in acute spinal cord compression injury rat model
title_full_unstemmed Agmatine inhibits nuclear factor-κB nuclear translocation in acute spinal cord compression injury rat model
title_short Agmatine inhibits nuclear factor-κB nuclear translocation in acute spinal cord compression injury rat model
title_sort agmatine inhibits nuclear factor κb nuclear translocation in acute spinal cord compression injury rat model
topic Spinal cord injury
Agmatine
Nuclear factor kappa B
Oxidative stress
Inflammation
Apoptosis
url http://www.sciencedirect.com/science/article/pii/S2090506815000706
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AT cherineaismail agmatineinhibitsnuclearfactorkbnucleartranslocationinacutespinalcordcompressioninjuryratmodel
AT monaahady agmatineinhibitsnuclearfactorkbnucleartranslocationinacutespinalcordcompressioninjuryratmodel
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