Abstract: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.
