The purpose of this study was to investigate the relationship between the improvement of motor function through training exercise simulating motor rehabilitation and myelination in the brain after HI injury, and to explore the new rehabilitation strategy that can improve motor function effectively.
We first investigated the effect of a training exercise on myelination in a neonatal HI rat model. The HI rat was made on postnatal day 7 (P7) by transecting the right common carotid artery (CCA) followed by hypoxic exposure with 8% O2 for 90 minutes. The rotarod task was performed from P21 to P42 as the motor assessment and training exercise. The latency to fall from the rotarod apparatus was measured as an index of motor function. After all behavioral experiments, the changes in myelin structure and oligodendrocytes (OLs) were verified by ex vivo diffusion tensor imaging (DTI) and immunohistochemistry (IHC).
We then examined the effectiveness of pharmacological promotion of myelination on motor improvement in HI rats. Clemastine was intraperitoneally injected every day from P22 to P42 before the start of the training exercise and observed behavioral changes using the rotarod task.
In the behavioral experiments, improved motor impairment was observed due to training exercises after HI injury. The latency to fall significantly extended due to training exercise in HI rats. The ex vivo DTI detected the changes of myelin structure in the primary somatosensory cortex (S1) ipsilateral to CCA trainsection in HI rats with a training exercise. IHC also revealed the changes in myelin structure and OLs in the S1. These results suggest the importance of myelination in motor improvement relating to training exercise after HI.
In the next experiment, the motor function in the rotarod task was evaluated in clemastine- and saline-injected HI rats with or without training exercises. The HI rats subjected to a training exercise and clemastine administration showed significantly longer latency compared to HI rats injected saline with training exercise and clemastine without training exercise, suggesting promoted motor improvement. Furthermore, in these animals, the structural changes of myelin sheaths and OLs in the S1 were also observed.
Myelination, including changes in OLs, can be important for motor improvement due to training exercises after neonatal HI. The clemastine administration promoting myelination can enhance the efficacy of training exercise, resulting in the promotion of motor improvement.
The combination of training exercise and clemastine administration can be a crucial strategy to lead to further motor improvement after HI injury.
motor
myelination
