Neuroprotective potential of ceftriaxone in in vitro models of stroke

Lipski, Janusz; Wan, Ck K.; Bai, Ji‐Zhong; Li, D.; Donnelly, David F.

doi:10.1016/j.neuroscience.2007.02.003

Cited by 141 publications

(142 citation statements)

References 66 publications

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“…Huber et al (1999) reported that in vitro pre-treatment with ampicillin (1 h before hypoxia) induces an increase in cellular hypoxic tolerance. It has also been reported that pre-treatment with ceftriaxone, one of the β-lactam antibiotics, exerts a neuroprotective effect in in vivo and in vitro models of brain ischemia and stroke (Chu et al, 2007;Lipski et al, 2007). Taken together, these data suggest that pre-ischemic treatment with ampicillin acts as a chemical pre- conditioning agent, resulting in the prevention of the ischemic neuronal damage induced by transient global forebrain ischemia.…”

Section: Discussionmentioning

confidence: 71%

“…The major forebrain astroglial glutamate transporter, GLT-1, plays an essential role in removing the glutamate that rapidly increases in the synaptic cleft within several minutes of ischemia/reperfusion (Anderson & Swanson, 2000;Rao et al, 2001;Swanson et al, 2004). It has been suggested that the neuroprotective effect of β-lactam antibiotics in vivo and in vitro is mediated by the induction of GLT-1 (Ji et al, 2005;Rothstein et al, 2005;Chu et al, 2007;Lipski et al, 2007;Lee et al, 2008). For instance, ceftriaxone, one of β-lactam antibiotics, induced upregulation of GLT-1 transduction and transcription along with the reduction of the mRNA levels of matrix metalloproteinase-9, tumor necrosis factor α and Fas ligand, thereby prevented neuronal cell death in an experimental stroke model (Chu et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

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Pre-ischemic Treatment with Ampicillin Reduces Neuronal Damage in the Mouse Hippocampus and Neostriatum after Transient Forebrain Ischemia

Lee

Kim

Cho

et al. 2008

Korean J Physiol Pharmacol

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Ampicillin, a β -lactam antibiotic, has been reported to induce astrocytic glutamate transporter-1 which plays a crucial role in protecting neurons against glutamate excitotoxicity. W e investigated the effect of ampicillin on neuronal damage in the mouse hippocampus and neostriatum following transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral occlusion of the common carotid artery for 40 min. Ampicillin was administered post-ischemically (for 3 days) and/or pre-ischemically (for 3∼ 5 days until one day before the onset of ischemia). Pre-and post-ischemic treatment with ampicillin (50 mg/kg/day or 200 mg/kg/day) prevented ischemic neuronal death in the medial CA1 area of the hippocampus as well as the neostriatum in a dose-dependent manner. In addition, ischemic neuronal damage was reduced by pre-ischemic treatment with ampicillin (200 mg/kg/day). In summary, our results suggest that ampicillin plays a functional role as a chemical preconditioning agent that protects hippocampal neurons from ischemic insult.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Pre-ischemic Treatment with Ampicillin Reduces Neuronal Damage in the Mouse Hippocampus and Neostriatum after Transient Forebrain Ischemia

Lee

Kim

Cho

et al. 2008

Korean J Physiol Pharmacol

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“…Following theoretical considerations, it may not be wise to use fluoroquinolones with glutaminergic effects such as ciprofloxacine or levofloxacine as first-line drugs in patients with acute stroke. Some antibiotics, in particular minocycline [55,56], and also β-lactam antibiotics such as ceftriaxone, used in the PASS trial [3], may exert neuroprotective properties [66,67]. Although the rate of complications from antibiotic drug therapy was almost negligible in most studies, the choice of antibiotic drug influences unwanted side effects from treatment.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic Antibiotic Therapy for Preventing Poststroke Infection

Schwarz

2016

Neurotherapeutics

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Infections, in particular pneumonia, are common complications in patients with acute stroke and are associated with a less favorable neurologic and functional outcome. Patients with severe stroke and dysphagia are at highest risk of infection. Experimental and clinical data suggest stroke-induced immunodeficiency as a major factor contributing to the high incidence of infection after stroke. Preclinical studies support the potential benefit of preventive antibiotic therapy in acute stroke for lowering the incidence of infection and improving clinical outcome. Several smaller clinical trials on preventive antibiotic therapy in patients with stroke conducted during the last 10 years yielded inconclusive results. Recently, 2 large, open-label, controlled trials failed to demonstrate an improved clinical outcome after preventive antibiotic therapy in patients with acute stroke treated in specialized stroke units. In the BPreventive Antibiotics in Stroke Study^, antibiotic therapy lowered the rate of infection but did not influence outcome. In the STROKE-INF study, performed in patients with dysphagia after stroke, antibiotic therapy did not lower the incidence of pneumonia and had no prognostic significance. At present, preventive antibiotic therapy cannot be recommended as a therapeutic option for acute stroke.

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“…Using this novel technique, we were successful in producing a focal infarct within the brain slice and a subsequent region of neuronal death that increased as a function of time. The major disadvantage of current in vitro ischemic models is that OGD solution is applied to the entire tissue (slice or cultured neurons) thus mimicking a global, rather than a focal ischemic event (Garcia de Arriba et al, 1999;Jarvis et al, 2001;Lipski et al, 2007). It can be argued that these models mimic the events that occur within the core region of a stroke but not the events that occur in the penumbra that still has a supply of both oxygen and glucose as compared to the core region.…”

Section: Discussionmentioning

confidence: 99%

“…This is referred to as global ischemia and thus the entire slice is representative of the "core". Although these models are used to characterize ischemiainduced neuronal death (Martínez-Sánchez et al, 2004) and have utility in identifying compounds that are neuroprotective (Lipski et al, 2007) or toxic (Bonde et al, 2003), they do not mimic the focal nature of stroke or the ability to study the events that occur within the penumbra. Consequently, using the existing global models, it is difficult to properly characterize the processes involved in the spread of cell death from the core to adjacent healthy tissue.…”

Section: E-mail Address: Tsaleh@upeica (Tm Saleh)mentioning

confidence: 99%

A novel method for inducing focal ischemia in vitro

Richard

Saleh

Bahh³

et al. 2010

Journal of Neuroscience Methods

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Current in vitro models of stroke involve applying oxygen-glucose deprived (OGD) media over an entire brain slice or plate of cultured neurons. Thus, these models fail to mimic the focal nature of stroke as observed clinically and with in vivo rodent models of stroke. Our aim was to develop a novel in vitro brain slice model of stroke that would mimic focal ischemia and thus allow for the investigation of events occurring in the penumbra. This was accomplished by focally applying OGD medium to a small portion of a brain slice while bathing the remainder of the slice with normal oxygenated media. This technique produced a focal infarct on the brain slice that increased as a function of time. Electrophysiological recordings made within the flow of the OGD solution ("core") revealed that neurons rapidly depolarized (anoxic depolarization; AD) in a manner similar to that observed in other stroke models. Edaravone, a known neuroprotectant, significantly delayed this onset of AD. Electrophysiological recordings made outside the flow of the OGD solution ("penumbra") revealed that neurons within this region progressively depolarized throughout the 75 min of OGD application. Edaravone attenuated this depolarization and doubled neuronal survival. Finally, synaptic transmission in the penumbra was abolished within 50 min of focal OGD application. These results suggest that this in vitro model mimics events that occur during focal ischemia in vivo and can be used to determine the efficacy of therapeutics that target neuronal survival in the core and/or penumbra.

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Neuroprotective potential of ceftriaxone in in vitro models of stroke

Cited by 141 publications

References 66 publications

Pre-ischemic Treatment with Ampicillin Reduces Neuronal Damage in the Mouse Hippocampus and Neostriatum after Transient Forebrain Ischemia

Pre-ischemic Treatment with Ampicillin Reduces Neuronal Damage in the Mouse Hippocampus and Neostriatum after Transient Forebrain Ischemia

Prophylactic Antibiotic Therapy for Preventing Poststroke Infection

A novel method for inducing focal ischemia in vitro

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