Hypothermia and erythropoietin for neuroprotection after neonatal brain damage

BACKGROUND: Both hypothermia and erythropoietin (EPO) are reported to have neuroprotective effects after perinatal hypoxia ischemia (HI). We investigated a possible additive effect of the use of a combination of hypothermia EPO in a rat model of neonatal HI. METHODS: At postnatal day 7, rats were subjected to HI and then randomized to 3 h of hypothermia, EPO; or both. Sensorimotor function was assessed by the cylinder-rearing test (CRT) at 2 and 5 wk after HI. Brain lesion volume and white matter loss were determined by hematoxylin eosin and luxol fast blue staining, respectively. RESULTS: Multivariable analysis using general linear modeling showed that hypothermia, EPO, and the interaction hypothermia x gender were determinants of sensorimotor function, both at 2 and 5 wk after HI. Neuroprotective effects of hypothermia at 5 wk were more pronounced in females, showing 52% improvement in the CRT. Maximal improvement in males was 26% after combined treatment with hypothermia and EPO. Histological outcome was improved by hypothermia only with no additional effect of EPO or gender. CONCLUSION: Hypothermia after HI improved sensorimotor function in females more than in males. There was a borderline additive effect of EPO when combined with hypothermia: Histology of brain lesion volume and white matter damage was improved only by hypothermia.