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Int. J. Mol. Sci. 2017, 18(11), 2311; https://doi.org/10.3390/ijms18112311

Diverse Effects of an Acetylcholinesterase Inhibitor, Donepezil, on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure

1
Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Korea
2
Department of Medical Science, College of Medicine, Hallym University, Chuncheon 24252, Korea
3
Faculty of Medical Sciences, Western University, London, ON N6A 5C1, Canada
4
College of Medicine, Neurology, Hallym University, Chuncheon 24252, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 28 September 2017 / Revised: 26 October 2017 / Accepted: 31 October 2017 / Published: 2 November 2017
(This article belongs to the Special Issue Neuroprotective Strategies 2017)
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Abstract

Epileptic seizures are short episodes of abnormal brain electrical activity. Many survivors of severe epilepsy display delayed neuronal death and permanent cognitive impairment. Donepezil is an acetylcholinesterase inhibitor and is an effective treatment agent for Alzheimer’s disease. However, the role of donepezil in seizure-induced hippocampal injury remains untested. Temporal lobe epilepsy (TLE) was induced by intraperitoneal injection of pilocarpine (25 mg/kg). Donepezil (2.5 mg/kg/day) was administered by gavage in three different settings: (1) pretreatment for three days before the seizure; (2) for one week immediately after the seizure; and (3) for three weeks from three weeks after the seizure. We found that donepezil showed mixed effects on seizure-induced brain injury, which were dependent on the treatment schedule. Pretreatment with donepezil aggravated neuronal death, oxidative injury, and microglia activation. Early treatment with donepezil for one week showed neither adverse nor beneficial effects; however, a treatment duration of three weeks starting three weeks after the seizure showed a significant reduction in neuronal death, oxidative injury, and microglia activation. In conclusion, donepezil has therapeutic effects when injected for three weeks after seizure activity subsides. Therefore, the present study suggests that the therapeutic use of donepezil for epilepsy patients requires a well-conceived strategy for administration. View Full-Text
Keywords: epilepsy; pilocarpine; donepezil; neuron death; oxidative injury; microglia activation epilepsy; pilocarpine; donepezil; neuron death; oxidative injury; microglia activation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Jeong, J.H.; Choi, B.Y.; Kho, A.R.; Lee, S.H.; Hong, D.K.; Lee, S.H.; Lee, S.Y.; Song, H.K.; Choi, H.C.; Suh, S.W. Diverse Effects of an Acetylcholinesterase Inhibitor, Donepezil, on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure. Int. J. Mol. Sci. 2017, 18, 2311.

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