Aspirin attenuates spontaneous recurrent seizures in the chronically epileptic mice

被引:13
作者
Zhu, Kun [1 ]
Hu, Ming [1 ,2 ]
Yuan, Bo [1 ]
Liu, Jian-Xin [1 ]
Liu, Yong [1 ]
机构
[1] Xi An Jiao Tong Univ, Inst Neurobiol, Sch Basic Med Sci, Hlth Sci Ctr, Xian, Peoples R China
[2] Xi An Jiao Tong Univ, Sch Basic Med Sci, Dept Human Anat Histol & Embryol, Hlth Sci Ctr, Xi'an, Peoples R China
基金
中国国家自然科学基金;
关键词
Aspirin; epilepsy; inflammation; neurogenesis; hippocampus; TEMPORAL-LOBE EPILEPSY; HIPPOCAMPAL NEURONAL LOSS; PILOCARPINE MODEL; MOUSE HIPPOCAMPUS; DENTATE GYRUS; ADULT BRAIN; NEUROGENESIS; CYCLOOXYGENASE-2; COX-2; RATS;
D O I
10.1080/01616412.2017.1326657
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: Neuroinflammatory processes are pathologic hallmarks of both experimental and human epilepsy, and could be implicated in the neuronal hyperexcitability. Aspirin represents one of the non-selective nonsteroidal anti-inflammatory drugs with fewer side effects in long-term application. This study was carried out to assess the anti-epileptic effects of aspirin when administered during the chronic stage of temporal lobe epilepsy [TLE] in mice. The alteration of hippocampal neurogenesis was also examined for raising a possible mechanism underlying the protective effect of anti-inflammatory treatment in the TLE. Methods: Two months after pilocarpine-induced status epilepticus, the chronically epileptic mice were treated with aspirin (20 mg, 60 mg or 80 mg/kg) once a day for 10 weeks. Spontaneous recurrent seizures were monitored by video camera for 2 weeks. To evaluate the profile of hippocampal neurogenesis, the newly generated cells in the dentate gyrus were labeled by the proliferation marker BrdU. The newborn neurons that extended axons to CA3 area were visualized by cholera toxin B subunit retrograde tracing. Results: Administration of aspirin with a dosage of 60 mg or 80 mg/kg initiated at 2 months after pilocarpine-induced status epilepticus significantly reduced the frequency and duration of spontaneous recurrent seizures. Aspirin treatment also increased the number of newborn neurons with anatomic integration through improving the survival of the newly generated cells. Conclusion: Aspirin treatment during the chronic stage of TLE could attenuate the spontaneous recurrent seizures in mice. Promotion of hippocampal neurogenesis and inhibition of COX-PGE2 pathway might partly contribute to this anti-epileptic effect.
引用
收藏
页码:744 / 757
页数:14
相关论文
共 56 条
[11]  
Flier S, 2008, CRIT CARE MED, V36, P2694, DOI 10.1097/CCM.0b013e3181843d69
[12]   Does aspirin use make it harder to collect seizures during elective video-EEG telemetry? [J].
Godfred, Rachel M. ;
Parikh, Mihir S. ;
Haltiner, Alan M. ;
Caylor, Lisa M. ;
Sepkuty, Jehuda P. ;
Doherty, Michael J. .
EPILEPSY & BEHAVIOR, 2013, 27 (01) :115-117
[13]   Emotion Recollected in Tranquility: Lessons Learned from the COX-2 Saga [J].
Grosser, Tilo ;
Yu, Ying ;
FitzGerald, Garret A. .
ANNUAL REVIEW OF MEDICINE, 2010, 61 :17-33
[14]   Hypoxia Markers are Expressed in Interneurons Exposed to Recurrent Seizures [J].
Gualtieri, Fabio ;
Marinelli, Carla ;
Longo, Daniela ;
Pugnaghi, Matteo ;
Nichelli, Paolo F. ;
Meletti, Stefano ;
Biagini, Giuseppe .
NEUROMOLECULAR MEDICINE, 2013, 15 (01) :133-146
[15]   Chronic temporal lobe epilepsy is dentate neurogenesis in the adult associated with severely declined hippocampus [J].
Hattiangady, B ;
Rao, MS ;
Shetty, AK .
NEUROBIOLOGY OF DISEASE, 2004, 17 (03) :473-490
[16]   Implications of decreased hippocampal neurogenesis in chronic temporal lobe epilepsy [J].
Hattiangady, Bharathi ;
Shetty, Ashok K. .
EPILEPSIA, 2008, 49 :26-41
[17]   Effects of SC58236, a selective COX-2 inhibitor, on epileptogenesis and spontaneous seizures in a rat model for temporal lobe epilepsy [J].
Holtman, L. ;
van Vliet, E. A. ;
van Schaik, R. ;
Queiroz, C. M. ;
Aronica, E. ;
Gorter, J. A. .
EPILEPSY RESEARCH, 2009, 84 (01) :56-66
[18]   Newly generated neurons at 2 months post-status epilepticus are functionally integrated into neuronal circuitry in mouse hippocampus [J].
Hu, Ming ;
Zhu, Kun ;
Chen, Xin-Lin ;
Zhang, Yao-Jie ;
Zhang, Jian-Shui ;
Xiao, Xin-Li ;
Liu, Jian-Xin ;
Liu, Yong .
EXPERIMENTAL NEUROLOGY, 2015, 273 :273-287
[19]   Environment matters: Synaptic properties of neurons born in the epileptic adult brain develop to reduce excitability [J].
Jakubs, Katherine ;
Nanobashvili, Avtandil ;
Bonde, Sara ;
Ekdahl, Christine T. ;
Kokaia, Zaal ;
Kokaia, Merab ;
Lindvall, Olle .
NEURON, 2006, 52 (06) :1047-1059
[20]   Influence of Aspirin on Pilocarpine-Induced Epilepsy in Mice [J].
Jeong, Kyoung Hoon ;
Kim, Joo Youn ;
Choi, Yun-Sik ;
Lee, Mun-Yong ;
Kim, Seong Yun .
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY, 2013, 17 (01) :15-21