Effects of Ceftriaxone on Oxidative Stress and Inflammation in a Rat Model of Chronic Cerebral Hypoperfusion

Ceftriaxone (CTX) exerts a neuroprotective effect by decreasing glutamate excitotoxicity. We further studied the underlying mechanisms and effects of CTX early post-treatment on behavior in a cerebral hypoperfusion rats. The rats’ common carotid arteries (2VO) were permanently ligated. CTX was treat...

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Main Authors: Apsorn Sattayakhom, Kosin Kalarat, Thatdao Rakmak, Sompol Tapechum, Arnaud Monteil, Chuchard Punsawad, Sarawoot Palipoch, Phanit Koomhin
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Behavioral Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-328X/12/8/287
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author Apsorn Sattayakhom
Kosin Kalarat
Thatdao Rakmak
Sompol Tapechum
Arnaud Monteil
Chuchard Punsawad
Sarawoot Palipoch
Phanit Koomhin
author_facet Apsorn Sattayakhom
Kosin Kalarat
Thatdao Rakmak
Sompol Tapechum
Arnaud Monteil
Chuchard Punsawad
Sarawoot Palipoch
Phanit Koomhin
author_sort Apsorn Sattayakhom
collection DOAJ
description Ceftriaxone (CTX) exerts a neuroprotective effect by decreasing glutamate excitotoxicity. We further studied the underlying mechanisms and effects of CTX early post-treatment on behavior in a cerebral hypoperfusion rats. The rats’ common carotid arteries (2VO) were permanently ligated. CTX was treated after ischemia. Biochemical studies were performed to assess antioxidative stress and inflammation. Behavioral and histological studies were then tested on the ninth week after vessel ligation. The 2VO rats showed learning and memory deficits as well as working memory impairments without any motor weakness. The treatment with CTX was found to attenuate white matter damage, MDA production, and interleukin 1 beta and tumor necrosis factor alpha production, mainly in the hippocampal area. Moreover, CTX treatment could increase the expression of glia and the glial glutamate transporters, and the neuronal glutamate transporter. Taken together, our data indicate the neuroprotective mechanisms of CTX involving the upregulation of glutamate transporters’ expression. This increased expression contributes to a reduction in glutamate excitotoxicity and oxidative stress as well as pro-inflammatory cytokine production, thus resulting in the protection of neurons and tissue from further damage. The present study highlights the mechanism of the effect of CTX treatment and of the underlying ischemia-induced neuronal damage.
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spelling doaj.art-9637ddafdd184ff787e7ec2cbe03087e2023-11-30T23:12:35ZengMDPI AGBehavioral Sciences2076-328X2022-08-0112828710.3390/bs12080287Effects of Ceftriaxone on Oxidative Stress and Inflammation in a Rat Model of Chronic Cerebral HypoperfusionApsorn Sattayakhom0Kosin Kalarat1Thatdao Rakmak2Sompol Tapechum3Arnaud Monteil4Chuchard Punsawad5Sarawoot Palipoch6Phanit Koomhin7School of Allied Health Sciences, Walailak University, Nakhonsithammarat 80160, ThailandSchool of Informatics, Walailak University, Nakhonsithammarat 80160, ThailandSchool of Liberal Arts, Walailak University, Nakhonsithammarat 80160, ThailandDepartment of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandInstitutde Génomique Fonctionnelle, University of Montpellier, CNRS, INSERM, 34094 Montpellier, FranceSchool of Medicine, Walailak University, Nakhonsithammarat 80160, ThailandSchool of Medicine, Walailak University, Nakhonsithammarat 80160, ThailandCenter of Excellence in Innovation on Essential Oil, Walailak University, Nakhonsithammarat 80160, ThailandCeftriaxone (CTX) exerts a neuroprotective effect by decreasing glutamate excitotoxicity. We further studied the underlying mechanisms and effects of CTX early post-treatment on behavior in a cerebral hypoperfusion rats. The rats’ common carotid arteries (2VO) were permanently ligated. CTX was treated after ischemia. Biochemical studies were performed to assess antioxidative stress and inflammation. Behavioral and histological studies were then tested on the ninth week after vessel ligation. The 2VO rats showed learning and memory deficits as well as working memory impairments without any motor weakness. The treatment with CTX was found to attenuate white matter damage, MDA production, and interleukin 1 beta and tumor necrosis factor alpha production, mainly in the hippocampal area. Moreover, CTX treatment could increase the expression of glia and the glial glutamate transporters, and the neuronal glutamate transporter. Taken together, our data indicate the neuroprotective mechanisms of CTX involving the upregulation of glutamate transporters’ expression. This increased expression contributes to a reduction in glutamate excitotoxicity and oxidative stress as well as pro-inflammatory cytokine production, thus resulting in the protection of neurons and tissue from further damage. The present study highlights the mechanism of the effect of CTX treatment and of the underlying ischemia-induced neuronal damage.https://www.mdpi.com/2076-328X/12/8/287ceftriaxonewhite matter damageoxidative stressinflammation
spellingShingle Apsorn Sattayakhom
Kosin Kalarat
Thatdao Rakmak
Sompol Tapechum
Arnaud Monteil
Chuchard Punsawad
Sarawoot Palipoch
Phanit Koomhin
Effects of Ceftriaxone on Oxidative Stress and Inflammation in a Rat Model of Chronic Cerebral Hypoperfusion
Behavioral Sciences
ceftriaxone
white matter damage
oxidative stress
inflammation
title Effects of Ceftriaxone on Oxidative Stress and Inflammation in a Rat Model of Chronic Cerebral Hypoperfusion
title_full Effects of Ceftriaxone on Oxidative Stress and Inflammation in a Rat Model of Chronic Cerebral Hypoperfusion
title_fullStr Effects of Ceftriaxone on Oxidative Stress and Inflammation in a Rat Model of Chronic Cerebral Hypoperfusion
title_full_unstemmed Effects of Ceftriaxone on Oxidative Stress and Inflammation in a Rat Model of Chronic Cerebral Hypoperfusion
title_short Effects of Ceftriaxone on Oxidative Stress and Inflammation in a Rat Model of Chronic Cerebral Hypoperfusion
title_sort effects of ceftriaxone on oxidative stress and inflammation in a rat model of chronic cerebral hypoperfusion
topic ceftriaxone
white matter damage
oxidative stress
inflammation
url https://www.mdpi.com/2076-328X/12/8/287
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