Disorganization of Oligodendrocyte Development in the Layer II/III of the Sensorimotor Cortex Causes Motor Coordination

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ORIGINAL PAPER

Disorganization of Oligodendrocyte Development in the Layer II/III of the Sensorimotor Cortex Causes Motor Coordination Dysfunction in a Model of White Matter Injury in Neonatal Rats Yoshitomo Ueda1   · Sachiyo Misumi1 · Mina Suzuki1 · Shino Ogawa1,2 · Ruriko Nishigaki1 · Akimasa Ishida1 · Cha‑Gyun Jung1 · Hideki Hida1 

Received: 27 April 2017 / Revised: 21 June 2017 / Accepted: 7 July 2017 © Springer Science+Business Media, LLC 2017

Abstract  We previously established neonatal white matter injury (WMI) model rat that is made by right common carotid artery dissection at postnatal day 3, followed by 6% hypoxia for 60  min. This model has fewer oligodendrocyte progenitor cells and reduced myelin basic protein (MBP) positive areas in the sensorimotor cortex, but shows no apparent neuronal loss. However, how motor deficits are induced in this model is unclear. To elucidate the relationship between myelination disturbance and concomitant motor deficits, we first performed motor function tests (gait analysis, grip test, horizontal ladder test) and then analyzed myelination patterns in the sensorimotor cortex using transmission electron microscopy (TEM) and Contactin associated protein 1 (Caspr) staining in the neonatal WMI rats in adulthood. Behavioral tests revealed imbalanced motor coordination in this model. Motor deficit scores were higher in the neonatal WMI model, while hindlimb ladder stepping scores and forelimb grasping force were comparable

to controls. Prolonged forelimb swing times and decreased hindlimb paw angles on the injured side were revealed by gait analysis. TEM revealed no change in myelinated axon number and the area g-ratio in the layer II/III of the cortex. Electromyographical durations and latencies in the gluteus maximus in response to electrical stimulation of the brain area were unchanged in the model. Caspr staining revealed fewer positive dots in layers II/III of the WMI cortex, indicating fewer and/or longer myelin sheath. These data suggest that disorganization of oligodendrocyte development in layers II/III of the sensorimotor cortex relates to imbalanced motor coordination in the neonatal WMI model rat.

Electronic supplementary material  The online version of this article (doi:10.1007/s11064-017-2352-3) contains supplementary material, which is available to authorized users.

Although advances in perinatal medicine have increased the survival rates of preterm infants [1, 2], these infants

* Hideki Hida [email protected]‑cu.ac.jp

Akimasa Ishida a‑[email protected]‑cu.ac.jp

Yoshitomo Ueda [email protected]‑cu.ac.jp

Cha‑Gyun Jung [email protected]‑cu.ac.jp

Sachiyo Misumi s‑[email protected]‑cu.ac.jp

1



Departments of Neurophysiology and Brain Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho‑cho, Mizuho‑ku, Nagoya 467‑8601, Japan

2



Departments of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho‑cho, Mizuho‑ku, Nagoya 467‑8601, Japan

Keywords  Hypoxia–ischemia in