Differential effect of low and high frequency transcranial magnetic stimulation on cortical excitability and myelination after neonatal hypoxia in mice

Abstract

Premature infants are highly prone to intermittent hypoxic brain injury, which is linked to adverse motor, cognitive, and behavioral outcomes, including attention deficits, hyperactivity, and learning difficulties. Previous animal studies have revealed myelination deficits and increased glutamatergic synaptic strength in the sensory-motor cortex. This study examines the feasibility, safety, and therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) to improve central hypomyelination, reduce excessive glutamatergic transmission in cortical neurons after neonatal intermittent hypoxia (IH), and enhance behavioral outcomes. In a mouse model of neonatal IH brain injury, low-frequency (LF-rTMS) at 1 Hz or high-frequency (HF-rTMS) at 10 Hz was administered for 5 days shortly after the injury. The rTMS treatment did not cause apoptosis or inflammation. HF-rTMS notably ameliorated hypomyelination in the corticospinal tract in both the stimulated and non-stimulated hemispheres. LF-rTMS decreased hyperactivity in female IH mice and lowered the heightened glutamatergic synaptic excitability in motor cortex slices. The data suggest that rTMS can affect both myelination and synaptic excitability, leading to improved behavioral outcomes following neonatal hypoxic brain injury. These results support the potential of rTMS as an early intervention for neurological issues caused by perinatal hypoxia.