TREATMENT OF EXPERIMENTAL FOCAL ISCHEMIA IN RATS WITH LUBELUZOLE

Lubeluzole is a neuroprotective compound in the final stages of clinic al evaluation. We evaluated the effect of intravenous followed by intr aperitoneal doses of lubeluzole on histological outcome after reversib le tandem middle cerebral/common carotid artery occlusion in Long-Evan s rats, with particular emphasis on the time window of efficacy. Lubel uzole, started 15 min after the onset of ischemia, had no adverse phys iological or behavioral effects and reduced maximal infarct volume pro duced by 120 min or more of arterial occlusion by approximately 50%, f rom 143.2 +/- 11.8 to 73.3 +/- 18.4 mm(3) (p < 0.05). Lubeluzole did n ot prolong the duration of middle cerebral artery occlusion which coul d be tolerated before histological damage occurred. Lubeluzole was sti ll effective if started 30 min after the onset of ischemia (34% reduct ion of maximal infarct volume; p < 0.05), but not after delays of 60 o r 120 min. We conclude that lubeluzole has promise as a neuroprotectiv e drug, particularly for more severe strokes, but must be started very rapidly after the onset of ischemia to be effective. Copyright (C) 19 96 Elsevier Science Ltd