[논문]Neuroprotective effect of lithium after pilocarpine-induced status epilepticus in mice

Hong, Namgue; Choi, Yun-Sik; Kim, Seong Yun; Kim, Hee Jung

doi:10.4196/kjpp.2017.21.1.125

Neuroprotective effect of lithium after pilocarpine-induced status epilepticus in mice 원문보기

The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, v.21 no.1, 2017년, pp.125 - 131

Hong, Namgue (Department of Physiology, College of Medicine, Dankook University) , Choi, Yun-Sik (Department of Pharmaceutical Science and Technology, College of Health and Medical Science, Catholic University of Daegu) , Kim, Seong Yun (Department of Pharmacology, College of Medicine, The Catholic University of Korea) , Kim, Hee Jung (Department of Physiology, College of Medicine, Dankook University)

Abstract ▼ AI-Helper

Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage. The present study was designed to investigate the effects of lithium post-treatment on seizure susceptibility and hippocampal neuropathological changes following pilocarpine-induced status epilepticus. Status epilepticus was induced by administration of pilocarpine hydrochloride (320 mg/kg, i.p.) in C57BL/6 mice at 8 weeks of age. Lithium (80 mg/kg, i.p.) was administered 15 minutes after the pilocarpine injection. After the lithium injection, status epilepticus onset time and mortality were recorded. Lithium significantly delayed the onset time of status epilepticus and reduced mortality compared to the vehicle-treated group. Moreover, lithium effectively blocked pilocarpine-induced neuronal death in the hippocampus as estimated by cresyl violet and Fluoro-Jade B staining. However, lithium did not reduce glial activation following pilocarpine-induced status epilepticus. These results suggest that lithium has a neuroprotective effect and would be useful in the treatment of neurological disorders, in particular status epilepticus.

주제어

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문제 정의

This study was designed to investigate the effects of lithium on seizure susceptibility and hippocampal damages following pilocarpine-induced SE in mice. The data presented here suggest that lithium post-treatment reduces seizure susceptibility and mortality as well as neuronal death without exerting a pronounced effect on glial activation in the hippocampus.

제안 방법

Extensive reactive astrogliosis and microglial activation (microgliosis) have been associated with SE-induced neuropathological changes [18]. Therefore, we examined the effects of lithium on astrocytic and microglial changes by testing GFAP and CD11b immunoreactivity (astrocyte and microglia markers, respectively). At 3 days after pilocarpine-induced SE, more GFAP-labeled astrocytes were observed in CA1, CA3 and the hilus (Fig.

대상 데이터

(Tokyo, Japan). Fluoro-Jade B and glial fibrillary acidic protein (GFAP) were purchased from Millipore (Temecula, CA, USA). The CD11b antibody came from Abcam (Cambridge, MA, USA).
Lithium chloride, distrene plasticizer xylene (DPX), pilocarpine hydrochloride, potassium permanganate and cresyl violet acetate were purchased from Sigma-Aldrich (St. Louis, MO, USA) and atropine methyl nitrate was obtained from Tokyo Chemical Industry Co. (Tokyo, Japan). Fluoro-Jade B and glial fibrillary acidic protein (GFAP) were purchased from Millipore (Temecula, CA, USA).

데이터처리

Student’s t test was used for statistical comparisons (GraphPad Prism 5 software v5.01, San Diego, CA, USA).

이론/모형

Behavioral changes after the injection with pilocarpine hydrochloride were recorded according to Racine’s scale [14] as described in Materials and Methods.

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