Neonatal hypoxic ischemia in rats induces myelin injury and structural lateralization of sensorimotor connectivity

Neonatal hypoxic ischemia (HI) around the birth impairs structural and functional networks in the whole brain, leading residual motor impairment necessary for therapeutic intervention. Myelin, which is essential for sensorimotor functional improvement, increases around the birth but is susceptible to HI. However, the involvement of myelin injury in the structural network changes in the brain after HI remains unclear. To investigate this issue, we clarified the relationship between the brain's structural network and myelin injury by using HI rat model. The HI rat model was established by transecting the right common carotid artery (CCA) and exposure to a hypoxic environment containing 8% oxygen for 90 minutes. Using ex vivo diffusion tensor imaging (DTI) and immunohistology, the changes in myelin sheaths in the corpus callosum (CC) and the structural network of the whole brain were analyzed. HI rats showed significantly decreased fractional anisotropy and increased radial diffusivity in the CC ipsilateral to CCA transection compared with the Sham group (n = 6/group, p < 0.05, respectively). Immunohistology revealed a decreased myelin density in the ipsilateral CC of HI rats compared with the Sham group (n = 6/group, p < 0.05). Furthermore, in structural connectome analysis, HI rats showed significantly decreased connectivity in the ipsilateral hemisphere compared with Sham group (p < 0.01). Particularly, the ipsilateral M1-S1 and bilateral S1-striatum connectivity of HI rats showed significantly reduced tract numbers compared with Sham rats (p < 0.05, respectively). These results suggest myelin damage following HI disrupts structural connectivity in the ipsilateral hemisphere, including the M1-S1 and S1-striatum connectivity. Furthermore, these findings identified the S1-centered structural network alterations as key contributors to brain dysfunction, such as motor impairment, after HI, and could highlight these networks as potential targets for therapeutic interventions to promote functional recovery.