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Levetiracetam exposure during prenatal and postnatal period induces cognitive decline in rat offsprings, not completely prevented by Bacopa monnieri

  • Sudhishma , Sahana Devadasa Acharya ORCID logo EMAIL logo , Sheetal D. Ullal ORCID logo , Vandana Blossom , Amrita Parida and Nadira Noushida
Published/Copyright: July 20, 2021

Abstract

Objectives

Levetiracetam (LEV) is an antiepileptic recommended during pregnancy. Bacopa monneri is a medicinal herb used in Ayurveda for improvement of cognition. Data on effects of LEV and Bacopa on cognition is inadequate. The study evaluated the cognitive effects of LEV on rat offspring of dams exposed to LEV and whether pretreatment with Bacopa monnieri, inhibits the potential cognitive decline by LEV.

Methods

Pregnant rats were allocated into four groups of three rats each. Groups 1, 2, 3 and 4 received 2% gum acacia, LEV 270 mg/kg, LEV 270 mg/kg + Bacopa 100 mg/kg and LEV 270 mg/kg + Bacopa 200 mg/kg respectively during pregnancy and lactation. Three pups from all dams were chosen at random and exposed to passive avoidance, Hebb-Williams and Morris water maze tests to check for their cognition and relevant histopathology was done.

Results

In the passive avoidance model groups 3 and 4, showed an increase in escape latency compared with group 2, demonstrating an improved learning (p=0.05). In Hebb-Williams maze, the time taken to reach reward chamber by group 2 increased compared to group 1, p=0.006, showing cognitive decline. Neuronal count in hippocampus and prefrontal cortex decreased significantly in group 2, which improved in group 3 & 4 however there was distortion of architecture in group 4.

Conclusions

LEV exposure in intrauterine and neonatal period induced cognitive decline in rat offsprings and Bacopa 100 mg/kg prevented LEV induced cognitive decline. However safety of exposure to Bacopa during the gestation period has to be evaluated.


Corresponding author: Sahana Devadasa Acharya, (MBBS, MD), Associate Professor, Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 575001 Karnataka, India, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Approval was obtained from Institutional Animal Ethics Committed prior to conduct of study.

References

1. Sarangi, SC, Kakkar, AK, Kumar, R, Gupta, YK. Effect of lamotrigine, levetiracetam & topiramate on neurobehavioural parameters & oxidative stress in comparison with valproate in rats. Indian J Med Res 2016;144:104–11. https://doi.org/10.4103/0971-5916.193296.Search in Google Scholar PubMed PubMed Central

2. Gerard, EE, Meador, KJ. An update on maternal use of antiepileptic medications in pregnancy and neurodevelopment outcomes. J Pediatr Genet 2015;4:94–110. https://doi.org/10.1055/s-0035-1556741.Search in Google Scholar PubMed PubMed Central

3. Tural, S, Tekcan, A, Elbistan, M, Karakus, N, Ozyuker, H, Kara, N. Genotoxic effects of prenatal exposure to levetiracetam during pregnancy on rat offsprings. In Vivo 2015;29:77–82.Search in Google Scholar

4. Ozer, FD, Demirel, A, Dilsiz, OY, Aydin, M, Ozdemir, N, Uyanikgil, Y, et al.. Effect of levetiracetam on neural tube development and closure of the chick embryos in ovo. Childs Nerv Syst 2012;28:969–76. https://doi.org/10.1007/s00381-012-1758-0.Search in Google Scholar PubMed

5. Ijff, DM, Aldenkamp, AP. Cognitive side-effects of antiepileptic drugs in children. Handb Clin Neurol 2013;111:707–18. https://doi.org/10.1016/b978-0-444-52891-9.00073-7.Search in Google Scholar PubMed

6. Roodenrys, S, Booth, D, Bulzomi, S, Phipps, A, Micallef, C, Smoker, J. Chronic effects of brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology 2002;27:279–81. https://doi.org/10.1016/s0893-133x(01)00419-5.Search in Google Scholar

7. Kumar, N, Abichandani, LG, Thawani, V, Gharpure, KJ, Naidu, MUR, Venkat Ramana, G. Efficacy of standardized extract of Bacopa monnieri (Bacognize) on cognitive functions of medical students: a six-week, randomized placebo-controlled trial. Evid Based Complement Alternat Med 2016;2016:4103423. https://doi.org/10.1155/2016/4103423.Search in Google Scholar PubMed PubMed Central

8. Chaudhari, KS, Tiwari, NR, Tiwari, RR, Sharma, RS. Neurocognitive effect of nootropic drug brahmi (Bacopa monnieri) in Alzheimer's disease. Ann Neurosci 2017;24:111–22. https://doi.org/10.1159/000475900.Search in Google Scholar PubMed PubMed Central

9. Gosh, MN. Toxicity studies. In: Gosh, MN editors. Fundamentals of experimental pharmacology, II ed. Calcutta scientific book agency; 1984. pp. 153–8.Search in Google Scholar

10. Ahirwar, S, Tembhre, M, Gour, S, Namdeo, A. Anticholinesterase efficacy of Bacopa monnieri against the brain regions of rat - a novel approach to therapy for Alzheimer's disease. Asian J Exp Sci 2012;26:65–70.Search in Google Scholar

11. Sireeratawong, S, Jaijoy, K, Khonsung, P, Lertprasertsuk, N, Ingkaninan, K. Acute and chronic toxicities of Bacopa monnieri extract in Sprague-Dawley rats. BMC Compl Alternative Med 2016;16:249. https://doi.org/10.1186/s12906-016-1236-4.Search in Google Scholar PubMed PubMed Central

12. Parle, M, Singh, N, Vasudevan, M. Regular rehearsal helps in consolidation of long term memory. J Sports Sci Med 2006;5:80–8.Search in Google Scholar

13. Morris, R. Developments of water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 1984;11:47–60. https://doi.org/10.1016/0165-0270(84)90007-4.Search in Google Scholar PubMed

14. Madhyastha, S, Somayaji, SN, Rao, MS, Nalini, K, Bairy, KL. Effect of intracerebroventricular methotrexate on brain amines. Indian J Physiol Pharmacol 2005;49:427–35.Search in Google Scholar

15. Vollala, VR, Upadhaya, S, Nayak, S. Learning and memory-enhancing effect of Bacopa monniera in neonatal rats. Bratisl Lek Listy 2011;112:663–9. https://doi.org/10.1590/s1807-59322011000400023.Search in Google Scholar PubMed PubMed Central

16. Yoshimi, K, Iwata, N. A supplemental measure of stay-times in the light box on step-through passive avoidance. Jpn J Pharmacol 1995;67:211–8. https://doi.org/10.1254/jjp.67.211.Search in Google Scholar PubMed

17. Parle, M, Singh, N. Animal models for testing memory. Asia Pac J Pharmacol 2004;16:101–20.Search in Google Scholar

18. Rasalam, AD, Hailey, H, Williams, JHG, Moore, SJ, Turnpenny, PD, Lloyd, DJ, et al.. Characteristics of fetal anticonvulsant syndrome associated autistic disorder. Dev Med Child Neurol 2005;47:551–5. https://doi.org/10.1017/s0012162205001076.Search in Google Scholar PubMed

19. Shallcross, R, Bromley, RL, Irwin, B, Bonnett, LJ, Morrow, J, Baker, GA. Child development following in utero exposure: levetiracetam vs sodium valproate. Neurology 2011;76:383–9. https://doi.org/10.1212/wnl.0b013e3182088297.Search in Google Scholar

20. Manthey, D, Asimiadou, S, Stefovska, V, Kaindl, AM, Fassbender, J, Ikonomidou, C, et al.. Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat brain. Exp Neurol 2005;193:497–503. https://doi.org/10.1016/j.expneurol.2005.01.006.Search in Google Scholar PubMed

21. Sendrowski, K, Sobaniec, P, Poskrobko, E, Rusak, M, Sobaniec, W. Unfavourable effect of levetiracetam on cultured hippocampal neurons after hyperthermic injury. Pharmacol Rep 2017;69:462–8. https://doi.org/10.1016/j.pharep.2017.01.020.Search in Google Scholar PubMed

22. Kilicdag, H, Daglioglu, K, Erdogan, S, Guzel, A, Sencar, L, Polat, S, et al.. The effect of levetiracetam on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury. Pharmacol Rep 2013;89:355–60. https://doi.org/10.1016/j.earlhumdev.2012.12.002.Search in Google Scholar PubMed

23. Kim, J, Kondratyev, A, Gale, K. Antiepileptic drug induced neuronal cell death in the immature brain: effect of carbamazepine, topiramate and levetiracetam as monotherapy versus polytherapy. J Pharmacol Exp Therapeut 2007;323:165–73. https://doi.org/10.1124/jpet.107.126250.Search in Google Scholar PubMed

24. Rastogi, M, Ojha, RP, Prabhu, PC, Devi, BP, Agrawal, A, Dubey, GP. Prevention of age-associated neurodegeneration and promotion of healthy brain ageing in female wistar rats by long term use of bacosides. Biogerontology 2012;13:183–95. https://doi.org/10.1007/s10522-011-9367-y.Search in Google Scholar PubMed

Received: 2020-10-12
Accepted: 2021-07-05
Published Online: 2021-07-20

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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