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Acetyl-L-Carnitine Exerts Neuroprotective and Anticonvulsant Effect in Kainate Murine Model of Temporal Lobe Epilepsy

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Abstract

The most well-known type of focal epilepsy that is resistant to existing treatments is temporal lobe epilepsy (TLE), with seizure foci in various structures including temporal lobe, hippocampus, amygdala, entorhinal cortex, and subcortex. The most significant processes involved in the pathophysiology of temporal lobe epilepsy (TLE) are oxidative stress, inflammation, and pyroptosis. There are evidences indicating that acetyl-l-carnitine (ALC) has anti-oxidative, anti-inflammatory, and anti-pyroptotic effects. In the present study, rat model of TLE was induced by intrahippocampal kainate and animals received ALC (100 mg/kg, p.o.). ALC properly attenuated intensity of seizures and also incidence of kainate-induced status epilepticus (SE). As well, obtained findings showed that ALC can partially reverse hippocampal levels of MDA, ROS, SOD, TNFa, NF-kB, TLR4, GFAP, and caspase 1. Besides, treatment of kainate group with ALC exerted a protective effect against CA1 neuronal loss and abnormal mossy fiber sprouting (MFS). Conclusively, these results suggest that ALC is capable to attenuate kainate-induced SE which is somewhat mediated through its lowering of oxidative stress, neuroinflammation, and pyroptosis that are related to its neuroprotective effect.

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Availability of Data and Materials

The data sets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ALC:

Acetyl-l-carnitine

DG:

Dentate gyrus

GFAP:

Glial fibrillary acidic protein

GSH:

Reduced glutathione

Kainate:

Kainic acid

MDA:

Malondialdehyde

MFS:

Mossy fiber sprouting

NF-kB:

Nuclear factor-kappa B

SE:

Status epilepticus

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

SE:

Status epilepticus

TLE:

Temporal lobe epilepsy

TNF-α:

Tumor necrosis factor-α

TBA:

Thiobarbituric acid

TLR4:

Toll-like receptor 4

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Funding

This research study was the results of PhD student thesis project that was officially approved and supported by Iran University of Medical Sciences, Tehran, Iran (Grant no. 97–03-04–12735).

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Authors and Affiliations

  1. Student Research Committee, Iran University of Medical Sciences, Tehran, Iran

    Mahsa Tashakori-Miyanroudi, Samira Ramazi, Paria Hashemi & Morteza Nazari-Serenjeh

  2. Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Mahsa Tashakori-Miyanroudi & Tourandokht Baluchnejadmojarad

  3. Neurophysiology Research Center, Shahed University, Tehran, Iran

    Mehrdad Roghani

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  1. Mahsa Tashakori-Miyanroudi
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Contributions

M.T., S.R., P.H., and M.NS. performed experiments and collected data. T.B. and M.R. planned the study, supervised the conductance of experimental tests, analyzed data, and prepared the manuscript draft. All authors read the final version of the manuscript.

Corresponding author

Correspondence to Tourandokht Baluchnejadmojarad.

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Ethics Approval and Consent to Participate

All experimental procedures of this study were conducted under ethical committee supervision of Iran University of Medical sciences (Tehran, Iran) that was in accordance to NIH guidelines for the care and use of laboratory animals. All efforts were made to minimize number of animals and to lower their sufferings. Present study was approved by Institutional Ethics Committee of the Iran University of Medical Sciences (Approval ID: IR.IUMS.FMD.REC.1398.090).

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All authors have read the manuscript and approved its submission.

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Tashakori-Miyanroudi, M., Ramazi, S., Hashemi, P. et al. Acetyl-L-Carnitine Exerts Neuroprotective and Anticonvulsant Effect in Kainate Murine Model of Temporal Lobe Epilepsy. J Mol Neurosci 72, 1224–1233 (2022). https://doi.org/10.1007/s12031-022-01999-8

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