Short‐term effects of therapeutic hypothermia following hypoxia–ischemia in neonatal male and female rats. Issue 2 (17th December 2022)

• Record Type: Journal Article
• Authors: Zang, Janaína; Colucci, Anna Clara Machado; Tassinari, Isadora D'Ávila; Nunes, Ricardo Ribeiro; Andrade, Mirella Kielek Galvan; Spies, Francielle Fernandes; de Oliveira, Maikel Rosa; Durán‐Carabali, Luz Elena; Rigon, Paula; Netto, Carlos Alexandre; Paz, Ana Helena; de Fraga, Luciano Stürmer
• Is Part Of: International journal of developmental neuroscience. Volume 83:Issue 2(2023)
• Page Start: 165
• Page End: 177
• Publication Date: 2022-12-17
• Subjects: brain injury -- hypoxia–ischemia -- neurodevelopment -- neuroprotection -- therapeutic hypothermia; Developmental neurobiology -- Periodicals; Neurology -- Periodicals; Neurologie du développement -- Périodiques; Developmental neurobiology; Periodicals; 612.8
• DOI: 10.1002/jdn.10244
• Languages: English
• ISSNs: 0736-5748

Abstract

Abstract: Nowadays, the only treatment for human babies suffering from hypoxia–ischemia (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. Abstract : Therapeutic hypothermia showed short‐term neuroprotective effects after neonatal hypoxia‐schemia in male and female rats. Overall, hypothermia attenuated brain injury volume and reduced neuronal death and the number of degenerating neurons in the hippocampus. However, the response pattern depended on the sex and hippocampal region assessed. These results reinforce the need to evaluate both sexes separately in preclinical studies in order to define sex‐specific strategies for the use of therapeutic hypothermia in clinical practice.