Abstract Objective To investigate the long-term effect of oligodendrocyte precursor cell (OPC) transplantation on a rat model of white matter injury (WMI) in the preterm infant. Methods A total of 80 Sprague-Dawley rats aged 3 days were randomly divided into sham-operation group, model control group, 5-day ventricular/white matter transplantation group, 9-day ventricular/white matter transplantation group, 14-day ventricular/white matter transplantation group (n=10 each). All groups except the sham-operation group were treated with right common carotid artery ligation and hypoxia for 80 minutes to establish a rat model of WMI in the preterm infant. OPCs were prepared from the human fetal brain tissue (10-12 gestational weeks). At 5, 9, and 14 days after modeling, 3×105 OPCs were injected into the right lateral ventricle or white matter in each transplantation group, and myelin sheath and neurological function were evaluated under an electron microscope at ages of 60 and 90 days. Results Electron microscopy showed that at an age of 60 days, each transplantation group had a slight improvement in myelin sheath injury compared with the model control group; at an age of 90 days, each transplantation group had significantly thickened myelin sheath and reduced structural damage compared with the model control group, and the 14-day transplantation groups had the most significant changes. There were no significant differences in the degree of myelin sheath injury between the ventricular and white matter transplantation groups at different time points. At an age of 60 or 90 days, the transplantation groups had a significantly higher modified neurological severity score (mNSS) than the sham-operation group and a significantly lower mNSS than the model control group (P < 0.05). Conclusions OPC transplantation may have a long-term effect in the treatment of WMI in the preterm infant, and delayed transplantation may enhance its therapeutic effect.
WU Cheng-Jun,WANG Zhao-Yan,YANG Yin-Xiang et al. Long-term effect of oligodendrocyte precursor cell transplantation on a rat model of white matter injury in the preterm infant[J]. CJCP, 2017, 19(9): 1003-1007.
WU Cheng-Jun,WANG Zhao-Yan,YANG Yin-Xiang et al. Long-term effect of oligodendrocyte precursor cell transplantation on a rat model of white matter injury in the preterm infant[J]. CJCP, 2017, 19(9): 1003-1007.
Elitt CM, Rosenberg PA. The challenge of understanding cerebral white matter injury in the premature infant[J]. Neuroscience, 2014, 276:216-238.
[2]
Boulanger JJ, Messier C. From precursors to myelinating oligodendrocytes:contribution of intrinsic and extrinsic factors to white matter plasticity in the adult brain[J]. Neuroscience, 2014, 269:343-366.
[3]
Armstrong RC, Mierzwa AJ, Sullivan GM, et al. Myelin and oligodendrocyte lineage cells in white matter pathology and plasticity after traumatic brain injury[J]. Neuropharmacology, 2016, 110(Pt B):654-659.
[4]
Back SA, Luo NL, Borenstein NS, et al. Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury[J]. J Neurosci, 2001, 21(4):1302-1312.
[5]
Kawabata S, Takano M, Numasawa-Kuroiwa Y, et al. Grafted human iPS cell-derived oligodendrocyte precursor cells contribute to robust remyelination of demyelinated axons after spinal cord injury[J]. Stem Cell Reports, 2016, 6(1):1-8.
[6]
Fan HB, Chen LX, Qu XB, et al. Transplanted miR-219-overexpressing oligodendrocyte precursor cells promoted remyelination and improved functional recovery in a chronic demyelinated model[J]. Sci Rep, 2017, 7:41407.
[7]
Stadlin A, James A, Fiscus R, et al. Development of a postnatal 3-day-old rat model of mild hypoxic-ischemic brain injury[J]. Brain Res, 2003, 993(1-2):101-110.
Chen LX, Ma SM, Zhang P, et al. Neuroprotective effects of oligodendrocyte progenitor cell transplantation in premature rat brain following hypoxic-ischemic injury[J]. PLoS One, 2015, 10(3):e115997.
[10]
Volpe JJ. Systemic inflammation, oligodendroglial maturation, and the encephalopathy of prematurity[J]. Ann Neurol, 2011, 70(4):525-529.
[11]
Back SA. White matter injury in the preterm infant:pathology and mechanisms[J]. Acta Neuropathol, 2017.[Epub ahead of print]
[12]
Givogri MI, Galbiati F, Fasano S, et al. Oligodendroglial progenitor cell therapy limits central neurological deficits in mice with metachromatic leukodystrophy[J]. J Neurosci, 2006, 26(12):3109-3119.
[13]
Shuaib A, Murabit MA, Kanthan R, et al. The neuroprotective effects of gamma-vinyl GABA in transient global ischemia:a morphological study with early and delayed evaluations[J]. Neurosci Lett, 1996, 204(1-2):1-4.
[14]
Bugiani M, Postma N, Polder E, et al. Hyaluronan accumulation and arrested oligodendrocyte progenitor maturation in vanishing white matter disease[J]. Brain, 2013, 136(Pt 1):209-222.
[15]
Kinney HC. Human myelination and perinatal white matter disorders[J]. J Neurol Sci, 2005, 228(2):190-192.
[16]
Hagberg H, Mallard C, Ferriero DM, et al. The role of inflammation in perinatal brain injury[J]. Nat Rev Neurol, 2015, 11(4):192-208.