Abstract: Objective To investigate the effects of fasudil (FSD) on oligodendrocyte (OLs) maturation and myelination after white matter injury (WMI) in preterm rats. Methods Eighty male pups on postnatal day 2 (P2) were randomly divided into the sham group (n=30), the WMI group (n=25) and the FSD group (n=25). WMI model was established in the WMI group and the FSD group. After modeling, the FSD group received intraperitoneal injection of FSD［25 mg/(kg·d)］for 4 consecutive days. The WMI group and the sham group were given the same amount of saline. Neurofunctional severity score was used to evaluate the neurofunctional severity. TUNEL assay was used to determine the apoptosis of OLs, and immunofluorescence was performed to detect the expression levels of Olig2, Nkx2.2 and myelin basic protein (MBP). Western blot assay was used to detect the expression of MBP. The ultrastructure of corpus callosum and corona radiata was observed by electron micrograph, and the small excited postsynaptic current (mEPSC) was analyzed by electrophysiology in vitro. The balance test and the new object recognition test were used to evaluate the motor behavior of rats. Results The neurological severity score was significantly lower in the FSD group than that of the WMI group at 0.5, 1, 2 and 4 days postoperatively (P＜0.05). FSD treatment significantly decreased the density of total apoptotic cells and OLs apoptotic cells in corpus callosum and corona radiata (P＜0.05), and increased the density of Olig2+Nkx2.2+ cells and MBP volume fraction (P＜0.05). In addition, the number of myelinated axons in the corpus callosum and corona radiata of the WMI group was less than that of the sham group, while the FSD group had more myelinated axons than WMI group (P＜0.05). In vitro electrophysiological analysis showed that the frequency of mEPSC was significantly higher in the FSD group than that of the WMI group (P＜0.05). Behavioral test results showed that the frequency of foot slip was lower in the FSD group than that in the WMI group, and which showed better recognition ability. Conclusion FSD can induce OLs maturation, promote myelination and neural function recovery, and can be used as a feasible drug for the treatment of WMI in premature infants to promote clinical recovery.

Key words: premature birth, white matter, oligodendroglia, myelin sheath, rats, Sprague-Dawley, white matter injury,  oligodendrocyte, Fasudil