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Authors & Affiliations
Taichi Goto, Tomokazu Tsurugizawa, Yuji Komaki, Sunao Iwaki, Ichiro Takashima, Nobuo Kunori
Abstract
Neonatal hypoxic ischemia (HI) causes motor impairment affecting daily activity. Rehabilitation is frequently implemented to improve motor performance, but its effects are often insufficient for acquiring fine motor coordination. Recently, myelin plasticity has been pointed out necessary for improving motor skills. However, the significance of myelination for motor improvement after HI remains unclear.To address this issue, we investigated the effect of rehabilitation exercise on myelination in a neonatal HI rat model. We then examined the effectiveness of pharmacological promotion of myelination on motor improvement. The HI rat was made on postnatal day 7 (P7) by ligating the right common carotid artery followed by hypoxic exposure. The rotarod task was performed from P21 to P42 as a rehabilitation exercise. In the pharmacological experiment, clemastine was intraperitoneally injected from P22 to P42. After behavioral tasks, changes of myelin sheaths and oligodendrocytes (OLs) were verified by immunohistochemistry.In behavioral experiments, the latency to fall was shorter in the HI rats compared to the sham injured rats. However, the exercise to HI rats significantly increased latency to fall. The immunohistochemistry showed the increased myelin density and the number of OLs in the primary somatosensory cortex (S1) in the exercised HI rats, suggesting the involvement of myelin changes on motor improvement. Furthermore, the pharmacological treatment accelerated the motor improvement in rotarod task and increased myelin density and the number of OLs in the S1. These results suggest that myelin plasticity, including changes of OLs, could be important to improve motor function after neonatal HI.