PDF(Pubmed)
Abstract：
Neonatal hypoxia-ischemia (HI) results in behavioral deficits, characterized by neuronal injury and retarded myelin formation. To date, limited treatment methods are available to prevent or alleviate neurologic sequelae of HI. Intermittent theta-burst stimulation (iTBS), a non-invasive therapeutic procedure, is considered a promising therapeutic tool for treating some neurocognitive disorders and neuropsychiatric diseases. Hence, this study aims to investigate whether iTBS can prevent the negative behavioral manifestations of HI and explore the mechanisms for associations. We exposed postnatal day 10 Sprague-Dawley male and female rats to 2 h of hypoxia (6% O2) following right common carotid artery ligation, resulting in oligodendrocyte (OL) dysfunction, including reduced proliferation and differentiation of oligodendrocyte precursor cells (OPCs), decreased OL survival, and compromised myelin in the corpus callosum (CC) and hippocampal dentate gyrus (DG). These alterations were concomitant with cognitive dysfunction and depression-like behaviors. Crucially, early iTBS treatment (15 G, 190 s, seven days, initiated one day post-HI) significantly alleviated HI-caused myelin damage and mitigated the neurologic sequelae both in male and female rats. However, the late iTBS treatment (initiated 18 days after HI insult) could not significantly impact these behavioral deficits. In summary, our findings support that early iTBS treatment may be a promising strategy to improve HI-induced neurologic disability. The underlying mechanisms of iTBS treatment are associated with promoting the differentiation of OPCs and alleviating myelin damage.
摘要：
新生儿缺氧缺血（HI）导致行为缺陷，以神经元损伤和髓鞘形成延迟为特征。迄今为止,有限的治疗方法可用于预防或减轻HI的神经系统后遗症。间歇性θ脉冲刺激(iTBS),一种非侵入性的治疗方法,被认为是治疗一些神经认知障碍和神经精神疾病的有前途的治疗工具。因此，本研究旨在探讨iTBS是否能预防HI的负面行为表现，并探讨其关联机制。我们将出生后第10天Sprague-Dawley雄性和雌性大鼠暴露于右颈总动脉结扎后2小时的缺氧（6％O2），导致少突胶质细胞（OL）功能障碍，包括少突胶质细胞前体细胞（OPCs）的增殖和分化减少，降低OL存活率，call体（CC）和海马齿状回（DG）的髓鞘受损。这些改变伴随着认知功能障碍和抑郁样行为。至关重要的是，早期iTBS治疗（15G，190s,七天,HI后一天开始）显着减轻了HI引起的髓磷脂损伤，并减轻了雄性和雌性大鼠的神经系统后遗症。然而,后期iTBS治疗(HI损伤后18天开始)不能显著影响这些行为缺陷.总之,我们的研究结果支持早期iTBS治疗可能是改善HI诱发的神经系统残疾的有希望的策略.iTBS治疗的潜在机制与促进OPCs的分化和减轻髓鞘损伤有关。
