The Effect of Piracetam Administration on Cerebral Palsy Prevention in Rat Fetuses Born To Pregnant Rats by Determining Bdnf Levels in Brain Tissue

Authors

  • Dudy Aldiansyah Philosophy Doctor in Medicine Program, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia. and Department of Obstetrics and Gynaecology, Medical Faculty, Universitas Sumatera Utara, Medan, Indonesia./Department of Obstetrics and Gynaecology, Medical Faculty, Universitas Sumatera Utara, Medan, Indonesia. https://orcid.org/0000-0001-9601-2855
  • Sarma Nursani Lumbanraja Department of Obstetrics and Gynaecology, Medical Faculty, Universitas Sumatera Utara, Medan, Indonesia.
  • Khairul Putra Surbakti Departement of Neurology, Medical Faculty, Universitas Sumatera Utara, Medan, Indonesia.
  • Isti Ilmiati Fujiati Department of Community Medicine, Public Health, Faculty of Medicine, Universitas Sumatera Utara, Medan Indonesia.
  • Agus Sulistyono Department Obstetrics & Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

DOI:

https://doi.org/10.21123/bsj.2024.9588

Keywords:

BDNF, Cerebral palsy, GluN3A, piracetam, rats.

Abstract

Cerebral palsy is the most common cause of disability in children worldwide, estimated prevalence of 1.5–4 per 1000 children; the  higher prevalence in low-resource populations (up to 10 per 1000 children). Brain-derived neurotrophic factor (BDNF) is potent modulator of many neuronal functions that protect the newborn or developing brain from ischemic injury. The expression of GluN3A, which plays a neuroprotective role, is rapidly induced during cerebral ischemia and hypoxia. This study assessed the effect of piracetam administration on BDNF and GluN3A levels in the brain tissue to determine its potential to prevent cerebral palsy. In this experimental study with a post-test-only control group design, a rat model of cerebral palsy was established by injecting pregnant rats with LPS on gestation days 15, 17, and 19; piracetam was administered orally on day 10.5. BDNF and GluN3A protein levels and mRNA expression in the foetal brain tissue of 36 subjects were evaluated with enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR). BDNF and GluN3A protein levels in the foetal brain differed significantly between the control and treatment groups (p < 0.05). A decrease in the mRNA and protein levels of BDNF and GluN3A was observed in all treatment groups, but the statistical analysis of RT-PCR did not reveal significant differences between the control and treatment groups (p > 0.05). These results indicate that piracetam can prevent cerebral palsy in a foetal rat model established via prenatal LPS injection, as assessed by the protein expression of BDNF and GluN3A mRNA.

References

Joshua AV. Cerebral Palsy: An Overview of Etiology, Types and Comorbidities. OBM Neurobiol.2022; 6 (2): 1-30. https://doi.org/10.21926/obm.neurobiol.2202120

Reddy N, Doyle M, Hanagandi P, Taranath A, Dahmoush H, Krishnan P, et.al. Neuroradiological mimics of periventricular leukomalacia. J Child Neurol. 2022; 37(2): 151-167. https://doi.org/10.1177/08830738211026052

Khurana R, Shyamsundar K, Taank P, Singh A. Periventricular leukomalacia: an ophthalmic perspective. Med J Armed Forces India. 2021; 77(2): 147–153. https://doi.org/10.1016/j.mjafi.2020.05.013

Paul S, Nahar A, Bhagawati M, Kunwar AJ. A Review on Recent Advances of Cerebral Palsy. Oxid Med Cell Longev. 2022;2022:.2622310. https://doi.org/10.1155/2022/2622310

Moretto E, Murru L, Martano G, Sassone J, Passafaro M. Glutamatergic synapses in neurodevelopmental disorders.Prog Neuro-Psycho pharm. Biol Psychiatry. 2018; 84: 328 342.https://doi.org/10.1016/j.pnpbp.2017.09.014

Hanna H, Youness ER, Orban HAA, El-Bassyouni HT. BDNF as a potential predictive biomarker for patients with pediatric cerebral palsy. F1000 Res. 2022; 11: 1347.https://doi.org/10.12688/f1000research.127917.1.

Bossi S, Dhanasobhon D, Ellis-Davies GCR, Frontera J, de Brito Van Velze M, Lourenço J, et.al. GluN3A excitatory glycine receptors control adult cortical and amygdalar circuits. Neuron. 2022; 110(15): 2438–2454. https://doi.org/10.1016/j.neuron.2022.05.016

Abd Elmagid DS, Magdy H. Evaluation of risk factors for cerebral palsy. Egypt J Neurol Psychiatr Neurosurg. 2021; 57: 1-9. https://doi.org/10.1186/s41983-020-00265-1

Faradila F, Yuliarni S, Rika S, Nur I. Liputo. The Effect of Combination Ovariectomy and D-galactose Administration on Alzheimer’s Animal Model. Baghdad Sci J. 2022; 19(5):1021. http://dx.doi.org/10.21123/bsj.2022.5486

Ahmadi SAY, Beigi Boroujeni M, Pajouhi N, Hasanvand A, Hasanvand A, Jamei SB, et al. Effect of Testosterone Enanthate Modeling of Polycystic Ovary on Liver Irs-2 mRNA Expression in Rats: A Brief Report. Baghdad Sci J. 2021; 18(3): 0480. https://doi.org/10.21123/bsj.2021.18.3.0480

Kakooza-Mwesige A, Andrews C, Peterson S, Mangen FW, Eliasson AC, Forssberg H. Prevalence of cerebral palsy in Uganda: a population-based study. Lancet Glob Health. 2017; 5: 1275–82. https://doi.org/10.1016/S2214-109X(17)30374-1

Woods L, Perez-Garcia V, Hemberger M. Regulation of placental development and its impact on fetal growth—new insights from mouse models. Front endocrinol. 2018; 9: 570.https://doi.org/10.3389/fendo.2018.00570

Chaokromthong K, Sintao N. Sample size estimation using Yamane and Cochran and Krejcie and Morgan and green formulas and Cohen statistical power analysis by G* Power and comparisions. APHEIT International Journal. 2021; 10(2): 76-86.

Arifin WN, Zahiruddin WM. Sample size calculation in animal studies using resource equation approach. The Malays J Med Sci. 2017; 24(5): 101-105.https://doi.org/10.21315/mjms2017.24.5.11

Bernard D. Animal models of cerebral palsy. Dev Med Child Neurol. 2020; 6 (1): 4-4. https://doi.org/10.1111/dmcn.14397

Liu L, Fang L, Duan B, Wang Y, Cui Z, Yang L, et al. Multi-Hit White Matter Injury-Induced Cerebral Palsy Model Established by Perinatal Lipopolysaccharide Injection. Front Pediatr. 2022; 10: 867410. https://doi.org/10.3389/fped.2022.867410

Skrzypczak-Wiercioch A, Sałat K. Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use. Molecules (Basel, Switzerland). 2022; 7(17): 5481. https://doi.org/10.3390/molecules27175481

Shrestha S, Singh M, Mishra SP. The Effect of Piracetam on Valproic Acid Induced Congenital Malformations in Swiss Albino Mice. Nepal Med Coll J. 2019; 21(3): 204-209. https://doi.org/10.3126/nmcj.v21i3.26459

Zhao J, Bi W, Xiao S, Lan X, Cheng X, Zhang J, et al. Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. Sci Rep. 2019; 9: 5790. https://doi.org/10.1038/s41598-019-42286-8

Failla MD, Conley YP, Wagner AK. Brain-Derived Neurotrophic Factor (BDNF) in Traumatic Brain Injury-Related Mortality: Interrelationships between Genetics and Acute Systemic and Central Nervous System BDNF Profiles. Neurorehabil Neural Repair 2016; 30: 83–93. https://doi.org/10.1177/1545968315586465

Gustafsson D, Klang A, Thams S, Rostami E. The role of BDNF in experimental and clinical traumatic brain injury. Int J Mol Sci. 2021; 22(7): 3582. https://doi.org/10.3390/ijms22073582

Ng TK, Coughlan C, Heyn P C, Tagawa A, Carollo J J, Kua E H. Increased plasma brain-derived neurotrophic factor (BDNF) as a potential biomarker for and compensatory mechanism in mild cognitive impairment: a case-control study. Aging. 2021; 13(19): 22666-22689. https://doi.org/10.18632/aging.203598

Hansen SL, Lorentzen J, Pedersen LT, Hendrich FL, Jorsal M, Pingel J. Suboptimal 11nutrition and low physical activity are observed together with reduced plasma brain-derived neurotrophic Factor (BDNF) concentration in children with severe cerebral palsy (CP). Nutrients. 2019; 11(3): 620. https://doi.org/10.3390/nu11030620

Pérez-Otaño I, Larsen R S, Wesseling JF. Emerging roles of GluN3-containing NMDA receptors in the CNS. Nat Rev Neurosci. 2016; 17(10): 623-635. https://doi.org/10.1038/nrn.2016.92

Downloads

Issue

Section

article

How to Cite

1.
The Effect of Piracetam Administration on Cerebral Palsy Prevention in Rat Fetuses Born To Pregnant Rats by Determining Bdnf Levels in Brain Tissue. Baghdad Sci.J [Internet]. [cited 2024 Dec. 21];22(1). Available from: https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/9588