Molecular Biology Reports

, Volume 46, Issue 2, pp 1757–1773 | Cite as

Altered lipid metabolism in post-traumatic epileptic rat model: one proposed pathway

  • Niraj Kumar SrivastavaEmail author
  • Somnath Mukherjee
  • Rajkumar Sharma
  • Jharana Das
  • Rohan Sharma
  • Vikas Kumar
  • Neeraj Sinha
  • Deepak Sharma
Original Article


Post-traumatic epilepsy (PTE) is a common long-term risk associated with traumatic brain injury (TBI). PTE rat model, proposed by Willmore et al., is a well known model that mimics human PTE. The present study explored the lipid metabolism in this PTE rat model by using in vitro, high-resolution NMR (nuclear magnetic resonance) spectroscopy and lipid staining based investigations. The level of gene expression, cytokines and enzyme activity was estimated. Level of TG (triglycerides), PL (phospholipids) and CHOL (cholesterol) was found to increase in brain tissue of PTE rats. This is an indication of the altered lipid metabolism in PTE rats. Level of lipid peroxidation and cytokines was enhanced in the brain tissue of PTE rats. A positive correlation was also observed in cytokines vs. lipid peroxidation. These results make available the evidence of the oxidative stress induced damage or destruction of the lipid components and also the cause of the inflammatory events in PTE rats. Antioxidant enzyme activity and respective gene expression were found to increase in brain tissue of PTE rats. A positive correlation was also observed in antioxidant enzyme’s activity vs. respective enzyme gene expression and lipid peroxidation vs. activity of antioxidant enzymes. Such outcomes reflect the oxidative stress induced lipid damage responsible for production enhancement of antioxidant enzymes, which further responsible for enhancing the activity of antioxidant enzymes. A positive correlation was observed in lipid peroxidation vs. lipid components (TG, PL and CHOL) and provides the confirmatory verification of alteration in the level of lipid components. A negative correlation was observed in the level of cytokines and the quantity of TG. This showed that TG is consumed in the production of cytokines. MUA (Motor unit activity) is highly correlated with the level of LP and indicated that oxidative stress is responsible for the event of epileptogenesis. Positive correlation of MUA with RA (rearing activity) and MWM (Morris-water maze) showed that epileptogenesis also influences the memory of PTE rats. Overall results based analyses clearly indicate that the inflammatory activity and oxidative stress in brain tissue of PTE rats, which are responsible to establish a significant change in the lipid metabolism. This can be visualized through a well constructed possible pathway of altered lipid metabolism. This study will improve our understanding and approach in the field of epilepsy that need to be considered for the development of new drugs or therapy for patients with PTE.

Graphical abstract

Representation of the proposed pathway of altered lipid metabolism in posttraumatic epileptic rats.


Oxidative stress Post-traumatic epilepsy Phospholipids Lipid extraction Lipid components Abnormal lipid metabolism Metabolic pathway Iron-induced epileptic rat Neuronal membrane lipids Cholesterol Triglycerides 



Superoxide dismutase


Glutathione peroxidase




Lipid peroxidation






Total cholesterol


Fatty acids


Post-traumatic epilepsy


Traumatic brain injury






Morris-water maze


Open-field test



Niraj Kumar Srivastava wishes to thank Council of Scientific & Industrial Research (CSIR), Government of India, for their generous financial support. Dr. S. K. Mandal, a consultant statistician at CBMR (SGPGIMS, Lucknow) is gratefully acknowledged for statistical analysis.


This work was funded by a Grant from the Council of Scientific & Industrial Research (CSIR), Government of India, in the form of CSIR-SRA (Senior research associate) [No. 13 (8660-A) 2013-Pool].

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest in any form related to the research work.

Ethical approval

All experimental protocols were approved by the Committee for the Purpose of Control and Supervision of Experimental Animals (CPCSEA) and the Institutional Animal Ethical Committee (IAEC) of Jawaharlal Nehru University, New Delhi, India.


  1. 1.
    Cesnik E, Casetta I, Granieri E (2013) Post-traumatic epilepsy: review. J Neurol Neurophysiol S2:009Google Scholar
  2. 2.
    Sharma V, Babu PP, Singh A, Singh S, Singh R (2007) Iron-induced experimental cortical seizures: electroencephalographic mapping of seizure spread in the subcortical brain areas. Seizure 16:680–690CrossRefPubMedGoogle Scholar
  3. 3.
    Jyoti A, Sethi P, Sharma D (2009) Aging accelerates the progression and manifestation of seizures in post-traumatic model of epilepsy. Neurosci Lett 453:86–91CrossRefPubMedGoogle Scholar
  4. 4.
    Streit WJ, Sammons NW, Kuhns AJ, Sparks DL (2004) Dystrophic microglia in the aging human brain. Glia 45:208–212CrossRefPubMedGoogle Scholar
  5. 5.
    Griffin WST (2006) Inflammation and neurodegenerative diseases. Am J Clin Nutr 83:470S–474SCrossRefPubMedGoogle Scholar
  6. 6.
    Jyoti A, Sethi P, Sharma D (2009) Curcumin protects against electro-behavioral progression of seizures in the iron-induced experimental model of epileptogenesis. Epilepsy Behav 14:300–308CrossRefPubMedGoogle Scholar
  7. 7.
    Mishra M, Singh R, Sharma D (2010) Antiepileptic action of exogenous dehydroepiandrosterone in iron-induced epilepsy in rat brain. Epilepsy Behav 19:264–271CrossRefPubMedGoogle Scholar
  8. 8.
    Singh R, Mishra M, Singh S, Sharma D (2012) Effect of l-deprenyl treatment on electrical activity, Na+, K + ATPase, and protein kinase C activities in hippocampal subfields (CA1 and CA3) of aged rat brain. Indian J Exp Biol 50:101–119PubMedGoogle Scholar
  9. 9.
    Mishra M, Singh R, Mukherjee S, Sharma D (2013) Dehydroepiandrosterone’s antiepileptic action in FeCl3-induced epileptogenesis involves up regulation of glutamate transporters. Epilepsy Res 106:83–91CrossRefPubMedGoogle Scholar
  10. 10.
    Das J, Singh R, Sharma D (2016) Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations. Nutr Neurosci 19:1–10CrossRefGoogle Scholar
  11. 11.
    Willmore LJ (1998) Epilepsy emergencies: the first seizure and status epilepticus. Neurology 51(5 Suppl 4):S34–S38CrossRefPubMedGoogle Scholar
  12. 12.
    Björkhem I, Meaney S (2004) Brain cholesterol: long secret life behind a barrier. ArteriosclerThromb Vasc Biol 24:806–815CrossRefGoogle Scholar
  13. 13.
    Mangiola A, VigoV, Anile C, De Bonis P, Marziali G, Lofrese G (2015) Role and importance of IGF-1 in traumatic brain injuries. Biomed Res Int 2015: 736104Google Scholar
  14. 14.
    Zhang J, Liu Q (2015) Cholesterol metabolism and homeostasis in the brain. Protein Cell 6:254–264CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Aynaci FM, Orhan F, Orem A, Yildirmis S, Gedik Y (2001) Effect of antiepileptic drugs on plasma lipoprotein (a) and other lipid levels in childhood. J Child Neur 16:367–369CrossRefGoogle Scholar
  16. 16.
    Fantini J, Yahi N (2015) Brain lipids in synaptic function and neurological disease: clues to innovative therapeutic strategies for brain disorders. Elsevier Academic Press, New YorkGoogle Scholar
  17. 17.
    Lehnhardt FG, Rohn G, Ernestus RI, Grune M, Hoehn M (2001) 1H and 31P-MR spectroscopy of primary and recurrent human brain tumors in vitro: malignancy-characteristics profiles of water soluble and lipophilic spectral components. NMR Biomed 14:307–317CrossRefPubMedGoogle Scholar
  18. 18.
    Kinoshita Y, Kajiwara H, Yokota A, Koga Y (1993) Proton magnetic resonance spectroscopy of astrocytic tumors: an in vitro study. Neurol Med Chir (Tokyo) 33:350–359CrossRefGoogle Scholar
  19. 19.
    Rzanny R, Klemm S, Reichenbach JR, Pfleiderer SO, Schmidt B, Volz HP, Blanz B, Kaiser WA (2003) 31P-MR spectroscopy in children and adolescents with a familial risk of schizophrenia. Eur Radiol 13:763–770PubMedGoogle Scholar
  20. 20.
    Srivastava NK, Pradhan S, Gowda GA, Kumar R (2010) In vitro, high-resolution 1H and 31P NMR based analysis of the lipid components in the tissue, serum, and CSF of the patients with primary brain tumors. NMR Biomed 23:113–122CrossRefPubMedGoogle Scholar
  21. 21.
    Adibhatla RM, Hatcher JF (2010) Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 12:125–169CrossRefPubMedGoogle Scholar
  22. 22.
    Patsoukis N, Zervoudakis G, Georgiou CD, Angelatou F, Matsokis NA, Panagopoulos NT (2005) Thiol redox state and lipid and protein oxidation in the mouse striatum after pentylenetetrazol-induced epileptic seizure. Epilepsia. 46:1205–1211CrossRefPubMedGoogle Scholar
  23. 23.
    Acharya MM, Katyare SS (2005) Structural and functional alterations in mitochondrial membrane in picrotoxin-induced epileptic rat brain. Exp Neurol 192:79–88CrossRefPubMedGoogle Scholar
  24. 24.
    Srivastava NK, Pradhan S, Mittal B, Gowda GA (2010) High resolution NMR based analysis of serum lipids in patients with duchenne muscular dystrophy and its possible diagnostic significance. NMR Biomed 23:13–22CrossRefPubMedGoogle Scholar
  25. 25.
    Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60CrossRefPubMedGoogle Scholar
  26. 26.
    Carrey N, McFadyen MP, Brown RE (2000) Effects of chronic methylphenidate administration on the locomotor and exploratory behaviour of prepubertal mice. J Child Adolesc Psychopharmacol 10:277–286CrossRefPubMedGoogle Scholar
  27. 27.
    El-Bahr SM (2013) Curcumin regulates gene expression of insulin like growth factor, B-cell CLL/lymphoma 2 and antioxidant enzymes in streptozotocin induced diabetic rats. BMC Complement Altern Med 13:368CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Singh RP, Padmavathi B, Rao AR (2000) Modulatory influence of Adhatodavesica (Justicia adhatoda) leaf extract on the enzymes of xenobiotic metabolism, antioxidant status and lipid peroxidation in mice. Mol Cell Biochem 213:99–109CrossRefPubMedGoogle Scholar
  29. 29.
    Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358CrossRefPubMedGoogle Scholar
  30. 30.
    Sharma S, Sahu D, Das HR, Sharma D (2011) Amelioration of collagen-induced arthritis by Salix nigra bark extract via suppression of pro-inflammatory cytokines and oxidative stress. Food Chem Toxicol 49:3395–3406CrossRefPubMedGoogle Scholar
  31. 31.
    Srivastava NK, Pradhan S, Mittal B, Kumar R, Gowda GA (2006) An improved, single step standardized method of lipid extraction from human skeletal muscle tissue. Anal Lett 39:297–315CrossRefGoogle Scholar
  32. 32.
    Srivastava NK, Pradhan S, Mittal B, Kumar R, Pandey CM, Gowda GA (2008) Novel corrective equations for complete estimation of human tissue lipids after their partial destruction by perchloric acid pre-treatment: high-resolution 1H-NMR-based study. NMR Biomed 21:89–100CrossRefPubMedGoogle Scholar
  33. 33.
    Srivastava NK, Sharma S, Purusottam RN, Sinha N, Singh R, Sharma D (2014) Abnormal lipid metabolism in collagen-induced-arthritis rat model: in vitro, high resolution NMR spectroscopy based analysis. Indian J Exp Biol 52:673–682PubMedGoogle Scholar
  34. 34.
    Adams CWM (1969) Lipid histochemistry. In: Advances in lipid research. 7, I. Academic Press, New YorkGoogle Scholar
  35. 35.
    Willmore LJ, Sypert GW, Munson JB, Hurd RW (1978) Chronic focal epileptiform discharges induced by injection of iron into cat cortex. Science 200:1501–1503CrossRefPubMedGoogle Scholar
  36. 36.
    Willmore LJ, Sypert GW, Munson JB (1978) Recurrent seizures induced by cortical iron injection: a model of post traumatic epilepsy. Ann Neurol 4:329–336CrossRefPubMedGoogle Scholar
  37. 37.
    Hernandes MS, Britto LRG (2012) NADPH oxidase and neurodegeneration. Curr Neuropharmacol 10:321–327CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Michiels C, Raes M, Toussaint O, Remacle J (1994) Importance of Se-glutathione peroxidase, catalase, and Cu/Zn–SOD for cell survival against oxidative stress. Free Radic Biol Med 17:235–248CrossRefPubMedGoogle Scholar
  39. 39.
    Tejada S, Roca C, Sureda A, Rial RV, Gamundí A, Esteban S (2006) Antioxidant response analysis in the brain after pilocarpine treatments. Brain Res Bull 69:587–592CrossRefPubMedGoogle Scholar
  40. 40.
    Srivastava NK, Srivastava AK, Mukherjee S, Sharma R, Mahapatra AK, Sharma D (2015) Determination of oxidative stress factors in patients with hereditary muscle diseases: one possible diagnostic and optional management of the patients. Int J Pharma Biosci 6(3):315–335Google Scholar
  41. 41.
    Lucke-Wold BP, Nguyen L, Turner RC, Logsdon AF, Chen YW, Smith KE, Huber JD, Matsumoto R, Rosen CL, Tucker ES, Richter E (2015) Traumatic brain injury and epilepsy: underlying mechanisms leading to seizure. Seizure 33:13–23CrossRefPubMedGoogle Scholar
  42. 42.
    Raphael R, David S, Strayer DS, Rubin E (2011) Rubin’s pathology: clinicopathologic foundations of medicine, 6th ed. Lippincott Williams & Wilkins, Philadelphia, pp. 62–66Google Scholar
  43. 43.
    Webster KM, Sun M, Crack P, O’Brien TJ, Shultz SR, Semple BD(2017) Inflammation in epileptogenesis after traumatic brain injury. J Neuroinflamm 14:10CrossRefGoogle Scholar
  44. 44.
    Hunt RF, Boychuk JA, Smith BN (2013) Neural circuit mechanisms of post-traumatic epilepsy. Front Cell Neurosci 7:89CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Malaisse WJ, Zhang Y, Louchami K, Sener A, Portois L, Carpentier YA (2006) Brain phospholipid and triglyceride fatty acid content and pattern in Type 1 and Type 2 diabetic rats. Neurosci Lett 409:75–79CrossRefPubMedGoogle Scholar
  46. 46.
    Arvin B, Neville LF, Barone FC, Feuerstein GZ (1996) The role of inflammation and cytokines in brain injury. Neurosci Biobehav Rev 20:445–452CrossRefPubMedGoogle Scholar
  47. 47.
    Ouchi N, Parker JL, Lugus JJ, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11:85–97CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Kontny E, Plebanczyk M, Lisowska B, Olszewska M, Maldyk P, Maslinski W (2012) Comparison of rheumatoid articular adipose and synovial tissue reactivity to proinflammatory stimuli: contribution to adipocytokine network. Ann Rheum Dis 71:262–267CrossRefPubMedGoogle Scholar
  49. 49.
    Dietschy JM, Turley SD (2004) Thematic review series: brain lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J Lipid Res 45:1375–1397CrossRefPubMedGoogle Scholar
  50. 50.
    Björkhem I, Meaney S (2004) Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol 24:806–815CrossRefPubMedGoogle Scholar
  51. 51.
    Cesnik E, Casetta I, Granieri E (2014) Post traumatic epilepsy: a review of triggers and potential treatments after brain injury. Int J Neurorehabilitation Eng 1:2Google Scholar
  52. 52.
    Sonmez FM, Demir E, Orem A, Yildirmis S, Orhan F, Aslan A, Topbas M (2006) Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes. J Child Neurol 21:70–74CrossRefPubMedGoogle Scholar
  53. 53.
    Schwaninger M, Ringleb P, Annecke A, Winter R, Kohl B, Werle E, Fiehn W, Rieser PA, Walter-Sack I (2000) Elevated plasma concentrations of lipoprotein (a) in medicated epileptic patients. J Neurol 247:687–690CrossRefPubMedGoogle Scholar
  54. 54.
    Van Horn JD, Bhattrai A, Irimia A (2017) Multimodal imaging of neurometabolic pathology due to traumatic brain injury. Trends Neurosci 40:39–59CrossRefPubMedGoogle Scholar
  55. 55.
    Fauvelle F, Boccard J, Cavarec F, Depaulis A, Deransart C (2015) Assessing susceptibility to epilepsy in three rat strains using brain metabolic profiling based on HRMAS NMR spectroscopy and chemometrics. J Proteome Res 14:2177–2189CrossRefPubMedGoogle Scholar
  56. 56.
    Horská A, Barker PB (2010) Imaging of brain tumors: MR spectroscopy and metabolic imaging. Neuroimag Clin North Am 20:293–310CrossRefGoogle Scholar
  57. 57.
    McKenna MC, Scafidi S, Robertson CL (2015) Metabolic alterations in developing brain after injury: knowns and unknowns. Neurochem Res 40:2527–2543CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Zeisel SH (1985) Formation of unesterified choline by rat brain. Biochim Biophys Acta 835: 331–343CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Niraj Kumar Srivastava
    • 1
    Email author
  • Somnath Mukherjee
    • 1
  • Rajkumar Sharma
    • 2
  • Jharana Das
    • 1
  • Rohan Sharma
    • 1
  • Vikas Kumar
    • 1
  • Neeraj Sinha
    • 2
  • Deepak Sharma
    • 1
  1. 1.School of Life SciencesJawaharlal Nehru UniversityNew DelhiIndia
  2. 2.Center of Biomedical Research (CBMR)Sanjay Gandhi Postgraduate Institute of Medical Sciences CampusLucknowIndia

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