Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
Dev Neurosci. 2024;46(4):273-284. doi: 10.1159/000534919. Epub 2023 Oct 31.
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.
目前治疗新生儿缺氧缺血性（HI）的唯一方法是治疗性低温（TH），但它仍存在一些局限性。TH 在脑损伤进展中涉及的几个过程中的具体作用尚不清楚。在这项研究中，我们评估了 TH 治疗对新生雄性和雌性大鼠发育参数、行为结果和外周白细胞的影响。在 P7 时，动物接受右侧颈总动脉闭塞（CCAO），随后缺氧（8%氧气）。通过将动物头皮温度降至 32°C 5 小时来进行 TH。评估行为参数和发育里程碑。动物在 P9 或 P21 时被安乐死，然后称重大脑半球、脾脏和胸腺。在血涂片上计数白细胞（WBC）。CCAO 后 HI 和 TH 组同侧大脑半球重量减轻，体重增加减少，同侧眼睛睁开延迟。HI 在 P12 时增加了负向趋地性的潜伏期。TH 不能预防脑重量减轻、发育障碍或白细胞数量变化，但能预防负向趋地性障碍和脾脏重量减轻。这些数据表明，需要更好地了解 HI 和 TH 后在雄性和雌性中发生的事件，这将允许开发更合适和性别特异性的治疗方法。
