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

Abstract

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.

Ceftriaxone has a neuroprotective effect in a whole brain irradiation-induced neurotoxicity model by increasing GLT-1 and reducing oxidative stress

“…Completely reversed GLT-1 levels were higher in the IR+CTX group compared to the IR-only group. Moreover, CTX treatment could increase the expression of glia and the glial glutamate transporters, and the neuronal glutamate transporter [12]. The neuroprotective activity of CTX has been documented in previous experimental animal models of cerebral ischemia, amyotrophic lateral sclerosis, Parkinson's disease, and epilepsy.…”

“…In an other study, a significant and marked upregulation of mRNA and protein expression of proinflammatory mediators, including TNF-α, IL-1β was observed in hippocampal and cortical regions isolated from irradiated brains [1,[34][35]. Also, it has been reported in a previous study that CTX treatment inhibited the production of IL-1 and TNF-α after the induction of cerebral ischemia [12].…”

“…Zou et al designed a study to reveal extracellular superoxide dismutase (EC-SOD) importance for hippocampal neurogenesis and preservation of cognitive functions after irradiation. It was reported that EC-SOD plays an important role in all stages of hippocampal neurogenesis and its associated cognitive functions and that high-level EC-SOD may protect against IR-associated defects in hippocampal functions [12].…”

“…The hippocampal area plays an essential role in learning and memory and is rich in glutamatergic synapses and Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which are vulnerable to excitotoxic damage [12,[47][48]. The effect of glutamate excitotoxicity on neuronal damage and the efficacy of CTX treatment were evaluated histopathologically.…”

“…One consequence of ROS generation is the initiation of glutamate excitotoxicity, which is modulated through the excessive activation of glutamate receptors [11]. Glutamate is a major neurotransmitter in the brain and spinal cord and plays critical roles in neuronal communication, neuronal growth, neuronal survival, and maturation [12].…”