Abstract WP58: Intermittent Theta-Burst Stimulation Attenuates Oligodendrocytes Dysfunction and Alleviates Depression-Like Behaviors in Hypoxia-Ischemia Rats

Abstract

Rationale: Perinatal hypoxic-ischemic (HI) brain injury is a significant cause of mortality and morbidity among newborns. Children who survive newborn hypoxic-ischemic encephalopathy (HIE) are at an increased risk of developing mood disturbances, 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) is considered a promising therapeutic tool for treating neuropsychiatric diseases. Hence, this study aims to investigate whether iTBS can prevent the negative behavioral manifestations of HI and explore the mechanisms for associations. Methods: Postnatal day 10 Sprague-Dawley male and female rats were subjected to hypoxic (6% O 2 ) conditions for 2 h after ligating the right common carotid artery. Transcranial application of iTBS (15 Gauss) was administered daily for seven consecutive days, starting either one day after HI insult (early iTBS) or 18 days after HI insult (late iTBS). Depression-like behaviors were examined 5 weeks after HI. The levels of oligodendrocyte progenitor cells (OPCs) proliferation, differentiation, and apoptosis, as well as the myelinating of oligodendrocytes (OLs) were measured and analyzed using immunofluorescence staining and automated western blot. Results: The male and female rats exposed to HI exhibited apparent OLs dysfunction, including a decrease in OPCs proliferation, a reduction in OPCs differentiation, diminished survival of OLs, and hindered myelination in the corpus callosum (CC) area. These alternations were concomitant with depression-like behaviors. Crucially, early iTBS treatment significantly alleviated HI-caused myelination damage and mitigated the neurologic sequelae both in male and female rats. However, the late iTBS treatment could not significantly impact these behavioral deficits. Conclusion: Our findings support that early iTBS treatment may be a promising strategy to improve HI-induced neurologic disability. The underlying mechanisms are suggested to be associated with the promoted the differentiation of OPCs and the alleviated myelination damage following iTBS administration.