This study assessed the capacity of β-lactam antibiotics to prevent salmonella-mediated encephalopathy in calves given the putative neuroprotective effects of these drugs of increasing glutamate export from the brain. Both ampicillin and ceftiofur prevented the development of encephalopathy despite resistance of the inoculated Salmonella enterica serovar Saint-Paul isolate to both drugs. A glutamate receptor antagonist also prevented this salmonella-mediated encephalopathy. Glutamate exporters were hyper-expressed in the presence of β-lactam antibiotics while a glutamate export inhibitor obviated the effects of these antibiotics, demonstrating a neuroprotective effect through glutamate export from the brain. The findings indicate that β-lactam antibiotics remain an important treatment option for this atypical form of bovine salmonellosis.
[Show abstract][Hide abstract] ABSTRACT: This manuscript considers available evidence that a specific Salmonella strain could be used as an effective orally-administered option for cancer therapy involving the brain. It has been established that Salmonella preferentially colonizes neoplastic tissue and thrives as a facultative anaerobe in the intra-tumor environment. Although Salmonella accumulates in tumors by passive processes, it is still possible for lipopolysaccharide to cause sepsis and endotoxic shock during the migration of bacteria to the tumor site. An LPS-free version of a recently identified Salmonella isolate may have the capability to circumvent the blood brain barrier and provide a safer method of reaching brain tumors. This isolate merits further research as a “Trojan horse” for future oral biotherapy of brain cancer.
Medical Hypotheses 09/2014; 83(3). DOI:10.1016/j.mehy.2014.06.009 · 1.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study assessed the involvement of lipopolysaccharide (LPS) in the non-typhoidal Salmonella encephalopathy (NTSE) caused by a unique isolate of Salmonella enterica serovar Saint-paul (SstpNPG). NTSE was prevented by genetic (deletion of murE) or pharmacologic (polymyxin) disruption of LPS on SstpNPG although the disruption of LPS did not deter brain penetration of the strain. This is the first study to demonstrate that LPS is involved in the manifestations of NTSE.
[Show abstract][Hide abstract] ABSTRACT: This review considers available evidence that some antibiotics have ancillary neuroprotective effects. Notably, β-lactam antibiotics are believed to increase the expression of glutamate transporter GLT1, potentially relieving the neurological excitotoxicity that characterizes disorders like amyotrophic lateral sclerosis. Minocycline has shown promise in reducing the severity of a number of neurological diseases, including multiple sclerosis, most likely by reducing apoptosis and the expression of inflammatory mediators in the brain. Rapamycin inhibits the activity of a serine/threonine protein kinase that has a role in the pathogenesis of numerous neurologic diseases. Herein we examine the unique neuroprotective aspects of these drugs originally developed as anti-infective agents.
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