Brandon Olivia C, White Olivia R, Corry Kylie A, Stanescu Andreea, Ariaye Arian, Moralejo Daniel H, Law Janessa B, Kolnik Sarah E, Juul Sandra E, Wood Thomas R
Division of Neonatology, University of Washington, Seattle, WA 98105, USA.
Institute on Human Development and Disability, University of Washington, Seattle, WA 98195, USA.
Life (Basel). 2025 Sep 11;15(9):1428. doi: 10.3390/life15091428.
Gyrification, the folding of the cerebral cortex, plays a crucial role in brain development and function. Perinatal hypoxia-ischemia (HI) is a leading cause of neonatal brain injury, affecting cortical folding that can be measured by the gyrification index (GI). Using a late-preterm ferret model, our objective was to explore the relationships between HI injury, GI changes, and behavior, as well as the potential moderating effects of sex and treatment. Animals received 3 mg/kg lipopolysaccharide and underwent bilateral carotid artery ligation followed by alternating hypoxia and hyperoxia (HIH) and were randomized to saline vehicle ( = 25), erythropoietin ( = 20), therapeutic hypothermia (6 h at 33.5 °C, = 20), and uridine monophosphate ( = 6), with = 20 unexposed littermates serving as controls. Early reflex testing, CatWalk gait analysis, open-field behavior, and an open-water swim test were performed. Average, peak, motor, and somatosensory strip GIs were then assessed using ex vivo MRI. In control animals, males had lower GI than females; however, HIH exposure resulted in male GI being more similar to females, where HIH animals had significantly higher average GI than controls ( = 0.02). Adjusting for brain volume and injury, GIs in motor and somatosensory areas were associated with faster reflex outcomes in males but not females. In female controls, motor and somatosensory GIs were associated with increased anxiety-like behaviors, such as spending less time in open water during the swim test. By comparison, in male controls, higher GI was associated with decreased anxiety-like behaviors, including higher exploration index in the swim test. These sex-specific relationships between GI and behavior were lost with HIH injury. Treatment did not meaningfully restore the relationship between GI and behavior after HIH, but targeting this outcome may be an important measure for use in future neuroprotection studies in the ferret.
脑回化，即大脑皮质的折叠，在大脑发育和功能中起着至关重要的作用。围产期缺氧缺血（HI）是新生儿脑损伤的主要原因，会影响可通过脑回化指数（GI）测量的皮质折叠。使用晚期早产雪貂模型，我们的目标是探索HI损伤、GI变化与行为之间的关系，以及性别和治疗的潜在调节作用。动物接受3mg/kg脂多糖，进行双侧颈动脉结扎，随后进行交替缺氧和高氧（HIH）处理，并随机分为生理盐水组（n = 25）、促红细胞生成素组（n = 20）、治疗性低温组（33.5℃ 6小时，n = 20）和单磷酸尿苷组（n = 6），20只未暴露的同窝幼崽作为对照。进行了早期反射测试、CatWalk步态分析、旷场行为测试和开放水域游泳测试。然后使用离体MRI评估平均、峰值、运动和体感皮层的GI。在对照动物中，雄性的GI低于雌性；然而，HIH暴露导致雄性的GI更接近雌性，HIH动物的平均GI显著高于对照组（P = 0.02）。在调整脑容量和损伤后，运动和体感区域的GI与雄性更快的反射结果相关，但与雌性无关。在雌性对照组中，运动和体感GI与焦虑样行为增加相关，例如在游泳测试中在开放水域停留的时间减少。相比之下，在雄性对照组中，较高的GI与焦虑样行为减少相关，包括游泳测试中较高的探索指数。HI损伤后，GI与行为之间的这些性别特异性关系消失。治疗在HIH后并未显著恢复GI与行为之间的关系，但针对这一结果可能是未来雪貂神经保护研究中的一项重要措施。
