Efek Pemberian Piracetam pada Kadar dan Ekspresi Interleukin-6, Glial Fibrillary Acidic Protein, Brain-Derived Neurotrophic Factor, mRNA Gelsolin, mRNA GluN3A, dan mRNA Calmodulin-2, pada Jaringan Otak Janin Tikus Model Periventricular Leukomalacia

Abstract

Introduction: Periventricular leukomalacia (PVL) is commonly found in cases of hypoxic ischemic encephalopathy, occurring due to perinatal damage to the cerebral cortex. This damage may be in the form of hypoxia, metabolic disturbances, prematurity, seizures, or infection. The periventricular area is most susceptible to damage due to its immaturity and vascular supply. Preterm birth and periventricular leukomalacia (PVL) are the main causes of cerebral palsy and cognitive deficits in preterm infants. Methods: Sixty-six rats were divided into 7 groups with 3 control groups, namely K1 (pregnant rats injected with LPS), K2 (pregnant rats without treatment), and K3 (pregnant rats injected with aquabidest or placebo) and 4 treatment groups, which were pregnant rats injected with LPS and piracetam drugs at various doses P1 (dose 50 mg/kgBW), P2 (dose 100 mg/kgBW), P3 (dose 150 mg/kgBW) and P4 (dose 200 mg/kgBW). Measurement of protein levels and mRNA expression of IL-6, GFAP, BDNF, Gelsolin, GluN3A and Calmodulin-2 were carried out in foetuses born prematurely and administered piracetam on day 19 of pregnancy. Protein levels and mRNA expression of IL-6, GFAP, BDNF, Gelsolin, GluN3A and Calmodulin-2 were examined using Enzyme Linked Immunosorbent Assay (ELISA) and real time PCR on brain tissue of rat fetuses born from pregnant rat models of periventricular leukomalacia. Data analysis was performed with a statistical program to see any differences in protein levels and mRNA expression of molecular proteins in the control group and the treatment group given piracetam at a dose of 50-200 mg/kgBW. One way Anova test was performed on samples with normal distribution and will be followed by LSD post-hoc test if p<0.05. Meanwhile, if the sample distribution is not normal, Kruskal-Wallis test will be performed and followed by Mann Whitney test if p<0.05. Results: This study found the drug piracetam can be used as a prevention of cerebral palsy in rat fetuses born from pregnant rats of periventricular leukomalacia models at doses of 50-200 mg kg/BW with the discovery of a significant decrease in the levels of molecular proteins IL-6, BDNF, GluN3A and Calmodulin-2 (p<0.05), found a statistically insignificant decrease in protein levels GFAP, Gelsolin (p>0.05). Conclusion: Piracetam administration can be used as a prevention of cerebral palsy in rat foetuses born in pregnant rats with periventricular leukomalacia models.