Therapeutic Hypothermia Is Limited in Preventing Developmental Impairments after Neonatal Hypoxia-Ischemia

Abstract

The only current treatment for neonatal hypoxia-ischemia (HI) is therapeutic hypothermia (TH), which still shows some limitations. Specific effects of TH in the several processes involved in brain injury progression remain unclear. In this study, the effects of TH treatment on developmental parameters, behavioral outcomes, and peripheral leukocytes were evaluated in neonatal male and female rats. In P7, animals were submitted to right common carotid artery occlusion followed by hypoxia (8% oxygen). TH was performed by reducing the animal scalp temperature to 32°C for 5 h. Behavioral parameters and developmental landmarks were evaluated. Animals were euthanized at P9 or P21, and cerebral hemispheres, spleen, and thymus were weighed. White blood cells (WBCs) were counted in blood smears. There was a reduction in the weight of the brain hemisphere ipsilateral to the carotid occlusion in HI and TH groups, as well as a reduction in body weight gain and a delay in the opening of the ipsilateral eye. Latency in negative geotaxis was increased by HI at P12. TH did not prevent brain weight loss, developmental impairments, or WBC number changes but prevented negative geotaxis impairment and spleen weight reduction. These data reinforce that a better understanding of the events that occur after HI and TH in both males and females is necessary and would allow the development of more adequate and sex-specific therapeutic approaches.