Short‐term effects of therapeutic hypothermia following hypoxia–ischemia in neonatal male and female rats

Abstract

Nowadays, the only treatment for human babies suffering from hypoxiaischemia (HI) is therapeutic hypothermia (TH). However, a better understanding of the specific effects of TH in males and females is important to improve its clinical application. The present study evaluated the short-term effects of TH on the brain injury and behavioral outcomes in male and female neonatal rats submitted to neonatal HI. Seven-day-old Wistar rats underwent a surgery for unilateral occlusion of the right common carotid artery and were exposed to a hypoxic atmosphere (8% oxygen) for 75 min. Then, the animals in the TH group were submitted to TH (scalp temperature of 32 C) for 5 h. In the behavioral tests, no remarkable differences triggered by HI or TH were observed relative to SHAM animals. Only females of the HI group presented lower latency to complete the righting reflex test. TH reduced the volume of brain injury in males, but not in females. The animals of the HI group showed a reduction in the number of neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus and TH partially prevented neuronal death. In the CA1 region of the hippocampus, animals from the HI group showed more degenerating cells relative to the SHAM, which was reversed by TH. In the DG, animals from the HI group showed an increase in the number of degenerating neurons, which was partially reversed by TH only in males. Our data show that HI leads to a brain injury, which was attenuated by TH in a sex-dependent way and clarify the importance of the assessment of males and females in order to outline specific strategies for the treatment of each sex in newborns suffering from HI.

Early Neuroprotective Effects of Bovine Lactoferrin Associated with Hypothermia after Neonatal Brain Hypoxia-Ischemia in Rats

“…The early evaluation of the developmental milestones after neonatal injuries can give valuable information of the efficacy of the therapeutic strategies [52][53][54]. We observed a general decrease in body weight in the animals fed with a LF diet, which could be interpreted as a detrimental effect of the diet.…”

“…The temperature was measured on the head ("scalp temperature") using an infrared thermometer (TFA SCANTEMP 330 ® ) every 10 min during Phase I (cooling) and Phase III (rewarm) of HT (initial and final 30 min). During Phase II (HT properly), the animals' head temperature was assessed every 30 min [52]. The average temperature during the hypothermia procedure is shown in Figure 16.…”