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Here, we have studied the capacity of an established therapeutic agent, magnesium, to improve survival in pneumococcal meningitis by modulating the neurological effects of the major pneumococcal pathogenic factor, pneumolysin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We used mixed primary glial and acute brain slice cultures, pneumolysin injection in infant rats, a mouse meningitis model and complementary approaches such as Western blot, a black lipid bilayer conductance assay and live imaging of primary glial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Treatment with therapeutic concentrations of magnesium chloride (500\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup> in animals and 2\u00a0mM in cultures) prevented pneumolysin\u2010induced brain swelling and tissue remodelling both in brain slices and in animal models. In contrast to other divalent ions, which diminish the membrane binding of pneumolysin in non\u2010therapeutic concentrations, magnesium delayed toxin\u2010driven pore formation without affecting its membrane binding or the conductance profile of its pores. Finally, magnesium prolonged the survival and improved clinical condition of mice with pneumococcal meningitis, in the absence of antibiotic treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Magnesium is a well\u2010established and safe therapeutic agent that has demonstrated capacity for attenuating pneumolysin\u2010triggered pathogenic effects on the brain. The improved animal survival and clinical condition in the meningitis model identifies magnesium as a promising candidate for adjunctive treatment of pneumococcal meningitis, together with antibiotic therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14027","type":"journal-article","created":{"date-parts":[[2017,9,9]],"date-time":"2017-09-09T18:18:40Z","timestamp":1504981120000},"page":"4295-4307","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Magnesium therapy improves outcome in <scp><i>Streptococcus pneumoniae<\/i><\/scp> meningitis by altering pneumolysin pore formation"],"prefix":"10.1111","volume":"174","author":[{"given":"Sabrina","family":"Hupp","sequence":"first","affiliation":[{"name":"Institute of Anatomy University of Bern  Bern Switzerland"},{"name":"DFG Membrane\/Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology &amp; Rudolf Virchow Center for Experimental Medicine University 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