Health Sciences Research Center (CICS-UBI), University of Beira Interior, 6201-506 Covilhã, Portugal.
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
Int J Mol Sci. 2022 Dec 23;24(1):257. doi: 10.3390/ijms24010257.
Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of death and long-term disability in the perinatal period. Currently, therapeutic hypothermia is the standard of care for this condition with modest efficacy and strict enrollment criteria. Therapy with umbilical cord blood cells (UCBC) has come forward as a strong candidate for the treatment of neonatal HIE, but no preclinical studies have yet compared the action of UCBC combined with hypothermia (HT) with the action of each therapy by itself. Thus, to evaluate the potential of each therapeutic approach, a hypoxic-ischemic brain lesion was induced in postnatal day ten rat pups; two hours later, HT was applied for 4 h; and 24, 48, and 72 h post-injury, UCBC were administered intravenously. The neonatal hypoxic-ischemic injury led to a brain lesion involving about 48% of the left hemisphere that was not improved by HT (36%) or UCBC alone (28%), but only with the combined therapies (25%; = 0.0294). Moreover, a decrease in glial reactivity and improved functional outcomes were observed in both groups treated with UCBC. Overall, these results support UCBC as a successful therapeutic approach for HIE, even when treatment with therapeutic hypothermia is not possible.
新生儿缺氧缺血性脑病（HIE）是围产期死亡和长期残疾的主要原因之一。目前，治疗性低温是这种疾病的标准治疗方法，疗效适度，且有严格的入组标准。脐带血细胞（UCBC）治疗已成为新生儿 HIE 治疗的有力候选方法，但尚无临床前研究比较 UCBC 联合低温（HT）与单独每种治疗方法的作用。因此，为了评估每种治疗方法的潜力，在出生后 10 天的大鼠幼崽中诱导缺氧缺血性脑损伤；两小时后，应用 HT 4 小时；损伤后 24、48 和 72 小时，静脉内给予 UCBC。新生儿缺氧缺血性损伤导致左半球约 48%的脑损伤，HT（36%）或单独 UCBC（28%）均未改善，但联合治疗仅改善了 25%（ = 0.0294）。此外，在接受 UCBC 治疗的两组中，均观察到神经胶质反应性降低和功能结局改善。总的来说，这些结果支持 UCBC 作为 HIE 的成功治疗方法，即使在无法进行治疗性低温治疗的情况下也是如此。
