The Novel Effect of Immunomodulator-Glatiramer Acetate on Epileptogenesis and Epileptic Seizures

Ming Chi Lai, Kao Min Lin, Poh Shiow Yeh, Sheng-Nan Wu, Chin-Wei Huang

研究成果: Article

摘要

Background/Aims: Immunological mechanisms can be triggered as a response to central nervous system insults and can lead to seizures. In this study an investigation was made to determine if glatiramer acetate (GA), an immunomodulator currently used in the treatment of multiple sclerosis, could protect rats from pilocarpine-induced seizures and chronic epilepsy. Methods: Two groups of adult male Sprague-Dawley rats, experimental (GA) and control, were used in the study. The systemic IL-1α and IL-1β levels at baseline were checked as well as status epilepticus (SE), and the spontaneous recurrent seizure (SRS) stage by enzyme-linked immunosorbent assay. The GA group was given GA (150 μg/kg, ip) and the control group was given a saline injection prior to pilocarpine-induced seizures. Seizure susceptibility, severity and mortality were evaluated, using Racine seizure classification and hippocampal damage was evaluated by Nissl staining. The GA group received GA (150 μg/kg/day, ip) daily after SE, and the chronic spontaneous seizures were evaluated by long-term video recording, and mossy fiber sprouting was evaluated by Timm staining. The IL-1α and IL-1β levels were correlated with seizure activities. The TNF-α level in the hippocampus was determined at the SRS stage by immunohistochemistry. The effect of GA on ionic currents and action potentials (APs) in NG108-15 differentiated neurons was investigated using patch-clamp technology. Results: It was found that latency to severe seizures was significantly longer in the GA (p < 0.01) group, which also had SE of shorter duration and less frequent SRS (p < 0.01). GA attenuated acute hippocampal neuron loss and chronic mossy fiber sprouting in the CA3 and the SRS-reduction correlated with the reduction of IL-1α, but not with IL-1β or TNF-α levels. Mechanistically, GA reduced the peak amplitude of voltage-gated Na + current (I Na ), with a negative shift in the inactivation curve of I Na and reduced the amplitude of APs along with decreased firing of APs. Conclusion: GA might serve as a neuroexcitability modulator which attenuates pilocarpine-induced acute and chronic excitotoxicity. Sodium channel attenuation was partially independent of the immunomodulatory effect.

原文English
頁(從 - 到)169-178
頁數10
期刊Cellular Physiology and Biochemistry
50
發行號1
DOIs
出版狀態Published - 2018 十月 1

指紋

Immunologic Factors
Epilepsy
Seizures
Interleukin-1
Pilocarpine
Status Epilepticus
Action Potentials
Glatiramer Acetate
Staining and Labeling
Neurons
Video Recording
Sodium Channels
Multiple Sclerosis
Sprague Dawley Rats
Hippocampus
Central Nervous System
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Technology

All Science Journal Classification (ASJC) codes

  • Physiology

引用此文

@article{f08543f0243e4715a25875d3baf3900e,
title = "The Novel Effect of Immunomodulator-Glatiramer Acetate on Epileptogenesis and Epileptic Seizures",
abstract = "Background/Aims: Immunological mechanisms can be triggered as a response to central nervous system insults and can lead to seizures. In this study an investigation was made to determine if glatiramer acetate (GA), an immunomodulator currently used in the treatment of multiple sclerosis, could protect rats from pilocarpine-induced seizures and chronic epilepsy. Methods: Two groups of adult male Sprague-Dawley rats, experimental (GA) and control, were used in the study. The systemic IL-1α and IL-1β levels at baseline were checked as well as status epilepticus (SE), and the spontaneous recurrent seizure (SRS) stage by enzyme-linked immunosorbent assay. The GA group was given GA (150 μg/kg, ip) and the control group was given a saline injection prior to pilocarpine-induced seizures. Seizure susceptibility, severity and mortality were evaluated, using Racine seizure classification and hippocampal damage was evaluated by Nissl staining. The GA group received GA (150 μg/kg/day, ip) daily after SE, and the chronic spontaneous seizures were evaluated by long-term video recording, and mossy fiber sprouting was evaluated by Timm staining. The IL-1α and IL-1β levels were correlated with seizure activities. The TNF-α level in the hippocampus was determined at the SRS stage by immunohistochemistry. The effect of GA on ionic currents and action potentials (APs) in NG108-15 differentiated neurons was investigated using patch-clamp technology. Results: It was found that latency to severe seizures was significantly longer in the GA (p < 0.01) group, which also had SE of shorter duration and less frequent SRS (p < 0.01). GA attenuated acute hippocampal neuron loss and chronic mossy fiber sprouting in the CA3 and the SRS-reduction correlated with the reduction of IL-1α, but not with IL-1β or TNF-α levels. Mechanistically, GA reduced the peak amplitude of voltage-gated Na + current (I Na ), with a negative shift in the inactivation curve of I Na and reduced the amplitude of APs along with decreased firing of APs. Conclusion: GA might serve as a neuroexcitability modulator which attenuates pilocarpine-induced acute and chronic excitotoxicity. Sodium channel attenuation was partially independent of the immunomodulatory effect.",
author = "Lai, {Ming Chi} and Lin, {Kao Min} and Yeh, {Poh Shiow} and Sheng-Nan Wu and Chin-Wei Huang",
year = "2018",
month = "10",
day = "1",
doi = "10.1159/000493965",
language = "English",
volume = "50",
pages = "169--178",
journal = "Cellular Physiology and Biochemistry",
issn = "1015-8987",
publisher = "S. Karger AG",
number = "1",

}

The Novel Effect of Immunomodulator-Glatiramer Acetate on Epileptogenesis and Epileptic Seizures. / Lai, Ming Chi; Lin, Kao Min; Yeh, Poh Shiow; Wu, Sheng-Nan; Huang, Chin-Wei.

於: Cellular Physiology and Biochemistry, 卷 50, 編號 1, 01.10.2018, p. 169-178.

研究成果: Article

TY - JOUR

T1 - The Novel Effect of Immunomodulator-Glatiramer Acetate on Epileptogenesis and Epileptic Seizures

AU - Lai, Ming Chi

AU - Lin, Kao Min

AU - Yeh, Poh Shiow

AU - Wu, Sheng-Nan

AU - Huang, Chin-Wei

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Background/Aims: Immunological mechanisms can be triggered as a response to central nervous system insults and can lead to seizures. In this study an investigation was made to determine if glatiramer acetate (GA), an immunomodulator currently used in the treatment of multiple sclerosis, could protect rats from pilocarpine-induced seizures and chronic epilepsy. Methods: Two groups of adult male Sprague-Dawley rats, experimental (GA) and control, were used in the study. The systemic IL-1α and IL-1β levels at baseline were checked as well as status epilepticus (SE), and the spontaneous recurrent seizure (SRS) stage by enzyme-linked immunosorbent assay. The GA group was given GA (150 μg/kg, ip) and the control group was given a saline injection prior to pilocarpine-induced seizures. Seizure susceptibility, severity and mortality were evaluated, using Racine seizure classification and hippocampal damage was evaluated by Nissl staining. The GA group received GA (150 μg/kg/day, ip) daily after SE, and the chronic spontaneous seizures were evaluated by long-term video recording, and mossy fiber sprouting was evaluated by Timm staining. The IL-1α and IL-1β levels were correlated with seizure activities. The TNF-α level in the hippocampus was determined at the SRS stage by immunohistochemistry. The effect of GA on ionic currents and action potentials (APs) in NG108-15 differentiated neurons was investigated using patch-clamp technology. Results: It was found that latency to severe seizures was significantly longer in the GA (p < 0.01) group, which also had SE of shorter duration and less frequent SRS (p < 0.01). GA attenuated acute hippocampal neuron loss and chronic mossy fiber sprouting in the CA3 and the SRS-reduction correlated with the reduction of IL-1α, but not with IL-1β or TNF-α levels. Mechanistically, GA reduced the peak amplitude of voltage-gated Na + current (I Na ), with a negative shift in the inactivation curve of I Na and reduced the amplitude of APs along with decreased firing of APs. Conclusion: GA might serve as a neuroexcitability modulator which attenuates pilocarpine-induced acute and chronic excitotoxicity. Sodium channel attenuation was partially independent of the immunomodulatory effect.

AB - Background/Aims: Immunological mechanisms can be triggered as a response to central nervous system insults and can lead to seizures. In this study an investigation was made to determine if glatiramer acetate (GA), an immunomodulator currently used in the treatment of multiple sclerosis, could protect rats from pilocarpine-induced seizures and chronic epilepsy. Methods: Two groups of adult male Sprague-Dawley rats, experimental (GA) and control, were used in the study. The systemic IL-1α and IL-1β levels at baseline were checked as well as status epilepticus (SE), and the spontaneous recurrent seizure (SRS) stage by enzyme-linked immunosorbent assay. The GA group was given GA (150 μg/kg, ip) and the control group was given a saline injection prior to pilocarpine-induced seizures. Seizure susceptibility, severity and mortality were evaluated, using Racine seizure classification and hippocampal damage was evaluated by Nissl staining. The GA group received GA (150 μg/kg/day, ip) daily after SE, and the chronic spontaneous seizures were evaluated by long-term video recording, and mossy fiber sprouting was evaluated by Timm staining. The IL-1α and IL-1β levels were correlated with seizure activities. The TNF-α level in the hippocampus was determined at the SRS stage by immunohistochemistry. The effect of GA on ionic currents and action potentials (APs) in NG108-15 differentiated neurons was investigated using patch-clamp technology. Results: It was found that latency to severe seizures was significantly longer in the GA (p < 0.01) group, which also had SE of shorter duration and less frequent SRS (p < 0.01). GA attenuated acute hippocampal neuron loss and chronic mossy fiber sprouting in the CA3 and the SRS-reduction correlated with the reduction of IL-1α, but not with IL-1β or TNF-α levels. Mechanistically, GA reduced the peak amplitude of voltage-gated Na + current (I Na ), with a negative shift in the inactivation curve of I Na and reduced the amplitude of APs along with decreased firing of APs. Conclusion: GA might serve as a neuroexcitability modulator which attenuates pilocarpine-induced acute and chronic excitotoxicity. Sodium channel attenuation was partially independent of the immunomodulatory effect.

UR - http://www.scopus.com/inward/record.url?scp=85054475806&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054475806&partnerID=8YFLogxK

U2 - 10.1159/000493965

DO - 10.1159/000493965

M3 - Article

C2 - 30278465

AN - SCOPUS:85054475806

VL - 50

SP - 169

EP - 178

JO - Cellular Physiology and Biochemistry

JF - Cellular Physiology and Biochemistry

SN - 1015-8987

IS - 1

ER -