Intermittent theta-burst stimulation alleviates hypoxia-ischemia-caused myelin damage and neurologic disability

• Published in: Experimental neurology 2024-08, Vol.378, p.114821, Article 114821
• Main Authors: Feng, Yu, Huang, Zhihai, Ma, Xiaohui, Zong, Xuemei, Xu, Peisheng, Lin, Hung Wen, Zhang, Quanguang
• Format: Article
• Language: English
• Subjects: Cognition; Depression; Intermittent theta-burst stimulation; Neonatal hypoxia-ischemia; Oligodendrocyte progenitor cells
• ISSN: 0014-4886; 1090-2430; 1090-2430
• DOI: 10.1016/j.expneurol.2024.114821

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. [Display omitted] •iTBS improves the cognitive dysfunction and depression-like behaviors of HI rats.•HI impairs the OPCs differentiation and damages the myelin of CC and DG area.•iTBS promotes the differentiation of OPCs and alleviates myelin damage of HI rats.