Effect of single or combined application of UDP-glucose, GDNF and memantine on improvement of white matter injury in neonatal rats assessed with light and electron microscopy pathologically

LI Wen-Juan; MAO Feng-Xia; CHEN Hui-Jin; QIAN Long-Hua

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Chinese Journal of Contemporary Pediatrics ›› 2012, Vol. 14 ›› Issue (12) : 964-970.

Effect of single or combined application of UDP-glucose, GDNF and memantine on improvement of white matter injury in neonatal rats assessed with light and electron microscopy pathologically

LI Wen-Juan, MAO Feng-Xia, CHEN Hui-Jin, QIAN Long-Hua

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Abstract

OBJECTIVE: To evaluate pathologically the effect of the single or combined application of UDP-glucose, GDNF and memantine on the improvement of white matter injury in neonatal rats with periventricular leukomalacia (PVL) under light and electron microscopy. METHODS: A five-day-old neonatal rat model for PVL was established by ligation of the lateral common carotid artery following 120-minute hypoxia. Rats were randomly divided into six groups (30 rats in each group): sham-operated, PVL, UDP-glucose (UDP-glucose 2000 mg/kg intraperitoneally after PVL), GDNF (GDNF 100 μg/kg intracerebrally after PVL), tmemantine (memantine 20 mg/kg intraperitoneally after PVL), and a combination administration of three drugs (UDP-glucose, GDNF and memantine). The rats were sacrificed 7 or 21 days after PVL for assessment of pathological changes in the white matter under both light and electron microscopy. The number and thickness of the myelin sheath in the white matter were measured under electron microscopy, and both of pathological grading and scoring were undertaken under light microscopy. RESULTS: There was rare and sparse myelinogenesis with a loose arrangement of nerve fibers in the white matter under electron microscopy in the PVL group at 7 and 21 days after PVL. The number and thickness of the myelin sheath in the PVL group were significantly less than in the sham-operated, UDP-glucose, GDNF, memantine and combination administration groups (P<0.01). The results of pathological grading of white matter under light microscopy showed that all rats in the PVL group manifested either mild injury (38%-50%) or severe injury (50%-62%) at 7 and 21 days after PVL. The majority of rats (50%-88%) in the four drug administration groups had normal white matter at 7 and 21 days after PVL. The pathological scores at 7 and 21 days after PVL in the PVL group were the highest, and they were significantly higher than in the other five groups (P<0.05). CONCLUSIONS: The single or combined application of UDP-glucose, GDNF and memantine may significantly improve pathological changes in the white matter of rats with PVL. The favorable effect is inferred to be closely correlated with the improvement of brain microenvironment and the enhancement of nerve regeneration promoted by the three drugs.

Key words

Periventricular leukomalacia / UDP-glucose / Glial cell line derived neurotrophic factor / Memantine / Rats

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LI Wen-Juan, MAO Feng-Xia, CHEN Hui-Jin, QIAN Long-Hua. Effect of single or combined application of UDP-glucose, GDNF and memantine on improvement of white matter injury in neonatal rats assessed with light and electron microscopy pathologically[J]. Chinese Journal of Contemporary Pediatrics. 2012, 14(12): 964-970

References

［1］Fagel DM, Ganat Y, Silbereis J, Ebbitt T, Stewart W, Zhang H, et al. Cortical neurogenesis enhanced by chronic perinatal hypoxia［J］. Exp Neurol, 2006, 199(1): 77-91.

［2］Lecca D, Trincavelli ML, Gelosa D, Sironi L, Ciana P, Fumaqalli M, et al. The recently identified P2Y-like receptor GPR17 is a sensor of brain damage and a new target for brain respair［J］. PLosS ONE, 2008, 3(10): 3579-3593.

［3］贺月秋, 陈惠金, 钱龙华, 陈冠仪. GDNF能增强神经干细胞经脑室移植治疗脑室周围白质软化新生大鼠的疗效［J］. 临床儿科杂志, 2009, 27(10): 963-970.

［4］Manning SM, Talos DM, Zhou C, Selip DB, Park HK, Park CJ, et al. NMDA receptor blockade with memantine attenuates white matter injury in a rat model of periventricular leukomalacia［J］. Neurosci, 2008, 28(26): 6670-6678.

［5］李文娟, 陈惠金，钱龙华, 何亚芳, 陈冠仪. GDNF、美金胺对脑室周围白质软化新生大鼠长期预后的影响研究［J］. 中国当代儿科杂志, 2011, 13(9): 743-746.

［6］贺月秋, 陈惠金, 钱龙华, 陈冠仪. 脑室周围白质软化新生大鼠模型的创建及所伴随的白内障病变［J］. 中国当代儿科杂志, 2007, 9（3）: 220-224.

［7］贺月秋, 陈惠金, 钱龙华, 陈冠仪. 不同缺血方式制作脑室周围白质软化大鼠模型的比较［J］. 实验动物与比较医学, 2010, 30(3): 153-157.

［8］Uehara H, Yoshioka H, Kawase S, Naqai H, Ohmae T, Haseqawa K, et al. A new model of white matter injury in neonatal rats with bilateral carotid artery occlusion［J］. Brain Res, 1999, 837(1-2): 213-220.

［9］Khwaja O, Volpe JJ. Pathogenesis of cerebral white injury of prematurity［J］. Arch Dis Child Fetal Neonatal Ed, 2008, 93(2): F153-F161.

［10］Bakiri Y, Burzomato V, Frugier G, Hamilton NB, Karadottir R, Attwell D. Glutamatergic signaling in the brain's white matter［J］. Neuroscience, 2009, 158(1): 266-274.

［11］Káradóttir R, Attwell D. Neurotransmitter receptors in the life and death of oligodendrocytes［J］. Neuroscience, 2007, 145(4): 1426-1438.

［12］Decressac M, Prestoz L, Veran J, Cantereau A, Jaber M, Gaillard A. Neuropeptide Y stimulates proliferation, migration and differentiation of neural precursors from the subventricular zone in adult mice［J］. Neurobiol Dis, 2009, 34(3): 441-449.

［13］Curtis MA, Kam M, Nannmark U, Anderson MF, Wikkelso C, Holtas S, et al. Human neuroblasts migrate to the olfactorybulb via a lateral ventricular extension［J］. Science, 2007, 315(5816): 1243-1249.

［14］Chandran S, Hunt D, Joannides A, Zhao C, Compston A, Franklin RJ, et al. Myelin repair: the role of stem and precursor cells in multiple sclerosis［J］. Philos Trans R Soc Lond B Biol Sci, 2007, 2019: 1-13.

［15］Ciana P, Fumagalli M, Trincavelli ML, Verderio C, Rosa P, Lecca D, et al. The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor［J］. EMBO J, 2006, 25(19): 4615-4627.

［16］Káradóttir R, Cavelier P, Bergersen LH, Attwell D. NMDA receptors are expressed in oligodendrocytes and activated in ischaemia［J］. Nature, 2005, 438(7071): 1162-1166.