The interleukin-8 (IL-8/CXCL8) receptor inhibitor reparixin improves neurological deficits and reduces long-term inflammation in permanent and transient cerebral ischemia in rats.
Leukocyte infiltration is viewed as a pharmacological target in cerebral ischemia. We previously reported that reparixin, a CXCL8 receptor blocker that inhibits neutrophil infiltration, and related molecules can reduce infarct size in a rat model of transient middle cerebral artery occlusion (MCAO). The study aims were to compare the effects of reparixin in transient and permanent MCAO using varied treatment schedules and therapeutic windows to evaluate effects on long-term neurological deficits and late inflammatory response. Reparixin, administered for 1 to 3 days, 3.5 to 6 h after MCAO, ameliorates neurological function recovery and inhibits long-term inflammation. The infarct size reduction at 24 h, evaluated by TTC staining, is more pronounced in transient MCAO. MRI analysis identified a decrease in the progression of infarct size by reparixin that was more evident at 48 h in permanent MCAO, and was associated with a significantly improved recovery from long-term neurological deficits.
Villa
Pia
P
Mario Negri Institute, 20157 Milan, Italy.
Triulzi
Sara
S
Cavalieri
Barbara
B
Di Bitondo
Rosa
R
Bertini
Riccardo
R
Barbera
Sara
S
Bigini
Paolo
P
Mennini
Tiziana
T
Gelosa
Paolo
P
Tremoli
Elena
E
Sironi
Luigi
L
Ghezzi
Pietro
P
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004334:Drug Administration Schedule; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000209:etiology / Q000601:surgery; D007249:Inflammation / Q000188:drug therapy*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D053700:Receptors, Interleukin-8 / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*
D018696:Neuroprotective Agents; D053700:Receptors, Interleukin-8; D013449:Sulfonamides; C490707:reparixin