Neonatal hypoxic ischemia in a rat induces a decrease in structural neural connectivity associated with myelin damage

Neonatal hypoxic ischemia (HI) impairs neural network in the brain, leading residual brain dysfunction. Myelin necessary for improvement of sensorimotor function is frequently injured owing to the coincidental timing of HI injury and oligodendrocyte development. 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 exposing to a hypoxic environment containing 8% oxygen. Using ex vivo DTI and immunohistological analysis, 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 that in Sham rats. Immunohistological analysis revealed a decreased myelin density in the ipsilateral CC of HI rats compared to Sham rats. Furthermore, in structural connectome analysis, HI rats showed a significant decreased connectivity in the ipsilateral hemisphere compared with Sham rats. Within the sensorimotor cortex, the ipsilateral M1-S1 connectivity, but not M1-M2 connectivity, of HI rats was significantly weakened compared to Sham rats. Bilateral S1-striatum connectivity also showed significantly decreased tracts after HI injury. These results suggest that myelin impairment from HI injury weakens the structural connectivity in the cerebral hemisphere ipsilateral to the CCA transection, particularly in the M1-S1 and S1-striatum connectivity.