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In the present study, we investigated the effects of selective inhibition of COX\u20102 with nimesulide (12\u2003mg\/kg) and selective inhibition of COX\u20101 with valeryl salicylate (VAS, 12\u2013120\u2003mg\/kg) on prostaglandin E<jats:sub>2<\/jats:sub>(PGE<jats:sub>2<\/jats:sub>) levels, myeloperoxidase (MPO) activity, Evans blue (EB) extravasation and infarct volume in a standardized model of transient focal cerebral ischaemia in the rat. Post\u2010ischaemic treatment with nimesulide markedly reduced the increase in PGE<jats:sub>2<\/jats:sub>levels in the ischaemic cerebral cortex 24\u2003h after stroke and diminished infarct size by 48% with respect to vehicle\u2010treated animals after 3\u2003days of reperfusion. Furthermore, nimesulide significantly attenuated the blood\u2013brain barrier (BBB) damage and leukocyte infiltration (as measured by EB leakage and MPO activity, respectively) seen at 48\u2003h after the initial ischaemic episode. These studies provide the first experimental evidence that COX\u20102 inhibition with nimesulide is able to limit BBB disruption and leukocyte infiltration following transient focal cerebral ischaemia. Neuroprotection afforded by nimesulide is observed even when the treatment is delayed until 6\u2003h after the onset of ischaemia, confirming a wide therapeutic window of COX\u20102 inhibitors in experimental stroke. On the contrary, selective inhibition of COX\u20101 with VAS had no significant effect on the evaluated parameters. These data suggest that COX\u20102 activity, but not COX\u20101 activity, contributes to the progression of focal ischaemic brain injury, and that the beneficial effects observed with non\u2010selective COX inhibitors are probably associated to COX\u20102 rather than to COX\u20101 inhibition.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2006.04280.x","type":"journal-article","created":{"date-parts":[[2006,12,15]],"date-time":"2006-12-15T00:56:29Z","timestamp":1166144189000},"page":"1108-1120","source":"Crossref","is-referenced-by-count":110,"title":["Post\u2010ischaemic treatment with the cyclooxygenase\u20102 inhibitor nimesulide reduces blood\u2013brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats"],"prefix":"10.1111","volume":"100","author":[{"given":"Eduardo","family":"Candelario\u2010Jalil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Gonz\u00e1lez\u2010Falc\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Garc\u00eda\u2010Cabrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga Sonia","family":"Le\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd L.","family":"Fiebich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007074420772"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.66010006.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20198"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-19-07724.2001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410506"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2003.12.016"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199908000-00001"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200005000-00007"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(96)00815-3"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)01499-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1992.9.363"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)02422-6"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(03)00184-6"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01812.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.01.078"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-2-3"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2006.01.003"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162468699"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1995.83.1.0099"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(02)00738-3"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000177814.41505.41"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.21.2019"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199611000-00035"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00367-4"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1368-5031.2006.00873.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.051490"},{"key":"e_1_2_8_28_1","first-page":"87","article-title":"Inflammation in stroke: the good, the bad, and the unknown","volume":"47","author":"Dirnagl U.","year":"2004","journal-title":"Ernst Schering Res. 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