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Effect of pranlukast on neonatal rats with periventricular leukomalacia
YE Xiao-Yan, WANG Da-Yu, XU Yan, WANG Jun
Chinese Journal of Contemporary Pediatrics ›› 2020, Vol. 22 ›› Issue (6) : 656-661.
PDF(2835 KB)
PDF(2835 KB)
Effect of pranlukast on neonatal rats with periventricular leukomalacia
Objective To study the effect of pranlukast (Pran) on neonatal rats with periventricular leukomalacia (PVL). Methods The rats, aged 3 days, were randomly divided into a sham-operation group, a PVL group, and a Pran group. A rat model of PVL was prepared by right common carotid artery ligation and postoperative hypoxia. The rats in the sham-operation group were given isolation of the right common carotid artery without ligation or hypoxic treatment. The rats in the Pran group were given intraperitoneal injection of Pran (0.1 mg/kg) once every 12 hours, for 3 consecutive days, and those in the sham-operation group and the PVL group were given intraperitoneal injection of an equal volume of normal saline. On day 14 after modeling, hematoxylin-eosin (HE) staining was used to observe the pathological changes of brain tissue; immunofluorescent staining was used to measure the expression of myelin basic protein (MBP) in brain tissue (n=8); Western blot was used to measure the expression of cyclic nucleotide phosphodiesterase (CNPase), MBP, and G protein-coupled receptor 17 (GPR17) (n=8). On day 21 after modeling, Morris water maze test was used to evaluate the learning and memory abilities of rats in each group (n=8). Results The results of HE staining showed that the PVL group had greater pathological changes of white matter than the sham-operation group, and compared with the PVL group, the Pran group had a significant improvement in such pathological changes. The results of immunofluorescence assay showed that the PVL group had a lower mean fluorescence intensity of MBP than the sham-operation group (P < 0.05), and the Pran group had a higher mean fluorescence intensity of MBP than the PVL group (P < 0.05). Western blot showed that compared with the sham-operation group, the PVL group had significantly lower relative expression of MBP and CNPase (P < 0.05) and significantly higher relative expression of GPR17 (P < 0.05), and compared with the PVL group, the Pran group had significantly higher relative expression of MBP and CNPase (P < 0.05) and significantly lower relative expression of GPR17 (P < 0.05). Morris water maze test showed that compared with the sham-operation group, the PVL group had a significant increase in escape latency and a significant reduction in the number of platform crossings, and compared with the PVL group, the Pran group had a significant reduction in escape latency and a significant increase in the number of platform crossings (P < 0.05). Conclusions Pran can alleviate brain damage, promote myelination, and improve long-term learning and memory abilities in neonatal rats with PVL, possibly by reducing the expression of GPR17.
Periventricular leukomalacia / Pranlukast / G protein-coupled receptor 17 / Rats
[1] Gotardo JW, Volkmer NFV, Stangler GP, et al. Impact of peri-intraventricular haemorrhage and periventricular leukomalacia in the neurodevelopment of preterms:a systematic review and meta-analysis[J]. PLoS One, 2019, 14(10):e0223427.
[2] Webber DJ, Van Blitterswijk M, Chandran S. Neuroprotective effect of oligodendrocyte precursor cell transplantation in a long-term model of periventricular leukomalacia[J]. Am J Pathol, 2009, 175(6):2332-2342.
[3] Alexandrou G, Mårtensson G, Skiöld B, et al. White matter microstructure is influenced by extremely preterm birth and neonatal respiratory factors[J]. Acta Paediatr, 2014, 103(1):48-56.
[4] Fumagalli M, Lecca D, Abbracchio MP, et al. CNS remyelination as a novel reparative approach to neurodegenerative diseases:the roles of purinergic signaling and the P2Y-like receptor GPR17[J]. Neuropharmacology, 2016, 104:82-93.
[5] Rahman SO, Singh RK, Hussain S, et al. A novel therapeutic potential of cysteinyl leukotrienes and their receptors modulation in the neurological complications associated with alzheimer's disease[J]. Eur J Pharmacol, 2019, 842:208-220.
[6] 贺月秋, 陈惠金, 钱龙华, 等. 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] Back SA. White matter injury in the preterm infant:pathology and mechanisms[J]. Acta Neuropathol, 2017, 134(3):331-349.
[8] Hagberg H, Peebles D, Mallard C, et al. Models of white matter injury:comparison of infectious, hypoxic-ischemic, and excitotoxic insults[J]. Ment Retard Dev Disabil Res Rev, 2002, 8(1):30-38.
[9] Craig A, Luo NL, Beardsley DJ, et al. Quantitative analysis of perinatal rodent oligodendrocyte lineage progression and its correlation with human[J]. Exp Neurol, 2003, 181(2):231-240.
[10] Alavi MS, Karimi G, Roohbakhsh A, et al. The role of orphan G protein-coupled receptors in the pathophysiology of multiple sclerosis:a review[J]. Life Sci, 2019, 224:33-40.
[11] Hennen S, Wang H, Peters L, et al. Decoding signaling and function of the orphan G protein-coupled receptor GPR17 with a small-molecule agonist[J]. Sci Signal, 2013, 6(298):ra93.
[12] Simon K, Hennen S, Merten N, et al. The orphan G protein-coupled receptor GPR17 negatively regulates oligodendrocyte differentiation via Gαi/o and its downstream effector molecules[J]. J Biol Chem, 2016, 291(2):705-718.
[13] Ou Z, Sun Y, Lin L, et al. Olig2-targeted G-protein-coupled receptor Gpr17 regulates oligodendrocyte survival in response to lysolecithin-induced demyelination[J]. J Neurosci, 2016, 36(41):10560-10573.
[14] Bonfanti E, Gelosa P, Fumagalli M, et al. The role of oligodendrocyte precursor cells expressing the GPR17 receptor in brain remodeling after stroke[J]. Cell Death Dis, 2017, 8(6):e2871.
[15] Marucci G, Dal ben D, Lambertucci C, et al. The G protein-coupled receptor GPR17:overview and update[J]. Chem Med Chem, 2016, 11(23):2567-2574.
[16] Draghi V, Wassink G, Zhou KQ, et al. Differential effects of slow rewarming after cerebral hypothermia on white matter recovery after global cerebral ischemia in near-term fetal sheep[J]. Sci Rep, 2019, 9(1):10142.
[17] Ahmadi M, Rajaei Z, Hadjzadeh MA, et al. Crocin improves spatial learning and memory deficits in the morris water maze via attenuating cortical oxidative damage in diabetic rats[J]. Neurosci Lett, 2017, 642:1-6.
