Fig. 8.

Graphs showing motor skills and seizure threshold deficits from prenatal TSHI are improved by neonatal rhEPO treatment. a: Insult rats demonstrate dose-responsive improvement in bar holding with neonatal EPO treatment. While a single low nonneuroprotective dose (500 IU/kg) of rEPO on postnatal Day 1, or 3 moderate doses (1000 IU/kg on postnatal Days 1–3) failed to produce significant improvement in individual time trials at postnatal Day 15 on the bar test compared with saline-treated insult rats, a high neuroprotective dose (2000 IU/kg on postnatal Days 1–5) induced significant improvement in insult rats (*p = 0.002, 2-way ANOVA), such that the insult rats were indistinguishable from control rats treated with saline. b: Stride length in adult rats is decreased after the prenatal insult (*p < 0.0001) compared with sham controls, and improves after high-dose neonatal rhEPO (2000 IU/kg for postnatal Days 1–5; **p = 0.014, 2-way ANOVA). c: Adult rats after the prenatal insult made more total errors on the horizontal ladder with irregular rungs than sham controls. Insult rats with high-dose neonatal rhEPO made significantly fewer total errors than saline-treated rats (**p = 0.006, 2-way ANOVA). d–f: The seizure threshold was lowered using PTZ, a GABA antagonist, in an escalating dose paradigm. Seizures were evaluated on a scale with 3 grades. The dose required to induce each seizure grade was significantly lower in postinsult rats, compared with sham controls (*Grade 1: p = 0.012; Grade II: p = 0.02; Grade III: p = 0.03). With high-dose neonatal rhEPO, the PTZ dose necessary to induce each grade of seizure in adult rats after the prenatal insult was significantly higher than in saline-treated postinsult rats (**Grade I: p = 0.0001; Grade II: p = 0.006; Grade III: p = 0.006; 2-way ANOVA), and comparable to doses for control rats.