Altered lipid metabolism in post-traumatic epileptic rat model: one proposed pathway
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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.
Representation of the proposed pathway of altered lipid metabolism in posttraumatic epileptic rats.
KeywordsOxidative stress Post-traumatic epilepsy Phospholipids Lipid extraction Lipid components Abnormal lipid metabolism Metabolic pathway Iron-induced epileptic rat Neuronal membrane lipids Cholesterol Triglycerides
Traumatic brain injury
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.
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.
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