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Demyelination on exposure to cuprizone is accompanied by predictable microglial activation and astrogliosis, and, after cuprizone withdrawal, this activation reproducibly diminishes during remyelination. This study demonstrates enhanced expression of lymphotoxin \u03b2 receptor (Lt\u03b2R) during the demyelination phase of this model, and Lt\u03b2R is found in areas enriched with microglial and astroglial cells. Deletion of the Lt\u03b2R gene (<jats:italic>Lt<\/jats:italic>\u03b2<jats:italic>R<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) resulted in a significant delay in demyelination but also a slight delay in remyelination. Inhibition of Lt\u03b2R signaling by an Lt\u03b2R\u2013Ig fusion decoy protein successfully delayed demyelination in wild-type mice. Unexpectedly, this Lt\u03b2R\u2013Ig decoy protein dramatically accelerated the rate of remyelination, even after the maximal pathological disease state had been reached. This strongly indicates the beneficial role of Lt\u03b2R\u2013Ig in the delay of demyelination and the acceleration of remyelination. The discrepancy between remyelination rates in these systems could be attributed to developmental abnormalities in the immune systems of<jats:italic>Lt<\/jats:italic>\u03b2<jats:italic>R<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. These findings bode well for the use of an inhibitory Lt\u03b2R\u2013Ig as a candidate biological therapy in demyelinating disorders, because it is beneficial during both demyelination and remyelination.<\/jats:p>","DOI":"10.1523\/jneurosci.1307-07.2007","type":"journal-article","created":{"date-parts":[[2007,7,11]],"date-time":"2007-07-11T19:13:45Z","timestamp":1184181225000},"page":"7429-7437","source":"Crossref","is-referenced-by-count":43,"title":["Lymphotoxin \u03b2 Receptor (Lt\u03b2R): Dual Roles in Demyelination and Remyelination and Successful Therapeutic Intervention Using Lt\u03b2R\u2013Ig Protein"],"prefix":"10.1523","volume":"27","author":[{"given":"Sheila R.","family":"Plant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A.","family":"Iocca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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