Gender differences in long-term beneficial effects of erythropoietin given after neonatal stroke in postnatal day-7 rats

Recently, we reported that erythropoletin attenuates neonatal brain injury caused by focal cerebral ischemia. The long-term effects of erythropoietin on focal cerebral ischemia-induced injury to the developing brain and the potential gender differences in these long-term effects have not been studied in detail. The current study demonstrated a similarity in the mean infarct volume in both the vehicle-treated male and female rats at 6 and 12 weeks after focal cerebral Schema. On the other hand, erythropoietin treatment (1000 U/kg x three doses after focal cerebral ischemia) caused a significant reduction in the mean infarct volume in both males and females at 6 weeks after focal cerebral ischemia when compared with the corresponding vehicle-treated animals (males: 141.4 +/- 48.2 mm(3) vs. 194.0 +/- 59.2 mm(3), P < 0.05; females: 85.4 +/- 31.6 mm(3) VS. 183.4 +/- 46.3 mm(3), P < 0.05). Interestingly, the reduction in the mean infarct volume in the erythropoletin-treated males was significantly less than that in the erythropoietin-treated females at 6 weeks after focal cerebral ischemia (141.4 +/- 48.2 mm(3) VS. 85.4 +/- 31.6 mm(3), P < 0.05). At 12 weeks after focal cerebral Ischernia, the mean infarct volume in the erythropoletintreated males significantly increased to 181.0 +/- 50.4 mm(3) (P < 0.05). In contrast, the mean infarct volume in the erythropoietin-treated females remained stable (87.0 +/- 41.7 mm(3)). Additionally, erythropoietin treatment significantly improved sensorimotor function recovery with a misstep number similar to the sham-operation group at 6 and 12 weeks after focal cerebral ischernia. Moreover, the mean number of missteps in the erythropoietin-treated females was less than that in males at 6 (13.5 +/- 2.0 vs. 24.5 +/- 2.5, P < 0.05) and 12 (12.5 +/- 2.0 vs. 20.0 +/- 2.0 P < 0.05) weeks after focal cerebral ischemia. These results indicate that erythropoietin administration after focal cerebral ischernia produces a significant long-term neuroprotective benefit on the developing brain, and that this effect is more beneficial in the female rats. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.