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Published on: April 21, 2017
Gender differences in long-term beneficial effects of erythropoietin given after neonatal stroke in postnatal day-7
1Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, USA. Tong_wen@oz.ped.emory.edu
Insights
Erythropoietin (EPO) offers long-term neuroprotection against neonatal brain injury from focal cerebral ischemia, with greater benefits observed in female rats. This treatment significantly reduces infarct volume and improves sensorimotor function in developing brains.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Neonatal brain injury from focal cerebral ischemia poses long-term risks.
- Erythropoietin (EPO) has shown promise in attenuating acute neonatal brain injury.
- Long-term effects and potential gender differences of EPO treatment require further investigation.
Purpose of the Study:
- To evaluate the long-term neuroprotective effects of erythropoietin (EPO) on focal cerebral ischemia-induced injury in the developing brain.
- To investigate potential gender-specific differences in the long-term efficacy of EPO treatment.
- To assess the impact of EPO on sensorimotor function recovery after neonatal focal cerebral ischemia.
Main Methods:
- Rats were subjected to focal cerebral ischemia and subsequently treated with either vehicle or erythropoietin (1000 U/kg x 3 doses).
- Infarct volume was measured at 6 and 12 weeks post-ischemia.
- Sensorimotor function was assessed using a misstep test at 6 and 12 weeks post-ischemia.
Main Results:
- Erythropoietin significantly reduced infarct volume in both male and female rats at 6 weeks post-ischemia compared to vehicle controls.
- The infarct volume reduction was significantly greater in female rats than in male rats at 6 weeks.
- At 12 weeks, infarct volume increased in male rats but remained stable in female rats, indicating sustained neuroprotection in females.
- Erythropoietin treatment significantly improved sensorimotor function in both sexes, with females showing better recovery than males at both time points.
Conclusions:
- Erythropoietin administration following focal cerebral ischemia provides significant long-term neuroprotection to the developing brain.
- The neuroprotective effects of erythropoietin are more pronounced and sustained in female rats compared to male rats.
- Erythropoietin treatment is a promising therapeutic strategy for mitigating long-term consequences of neonatal focal cerebral ischemia, with notable sex-specific benefits.
Abstract:
Recently, we reported that erythropoietin 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 ischemia. 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 mm3 vs. 194.0+/-59.2 mm3, P<0.05; females: 85.4+/-31.6 mm3 vs. 183.4+/-46.3 mm3, P<0.05). Interestingly, the reduction in the mean infarct volume in the erythropoietin-treated males was significantly less than that in the erythropoietin-treated females at 6 weeks after focal cerebral ischemia (141.4+/-48.2 mm3 vs. 85.4+/-31.6 mm3, P<0.05). At 12 weeks after focal cerebral ischemia, the mean infarct volume in the erythropoietin-treated males significantly increased to 181.0+/-50.4 mm3 (P<0.05). In contrast, the mean infarct volume in the erythropoietin-treated females remained stable (87.0+/-41.7 mm3). 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 ischemia. 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 ischemia produces a significant long-term neuroprotective benefit on the developing brain, and that this effect is more beneficial in the female rats.
