title: The Effects of Amiloride on Seizure Activity, Cognitive Deficits and Seizure-Induced Neurogenesis in a Novel Rat Model of Febrile Seizures.
abstract: Accumulating data suggest that sodium-hydrogen exchangers (NHEs) play a key role in modulating seizure activity by regulating neuronal pH in the brain. Amiloride, an inhibitor of NHEs, has been demonstrated to be effective in many seizure models, although its efficacy for prolonged febrile seizures (FS) remains unclear. In this study, we investigated whether amiloride could produce neuroprotective effects in a prolonged FS model in which FS were induced in rat pups at postnatal day 10 using a heated air approach. Amiloride was administered by intraperitoneal injection at three different doses (0.65, 1.3 and 2.6 mg/kg). Pretreatment with amiloride significantly delayed the onset of the first episode of limbic seizures, whereas posttreatment with amiloride decreased escape latency in the Morris water maze test compared to post-FS treatment with saline. Amiloride also inhibited seizure-induced aberrant neurogenesis. In conclusion, this study demonstrated the antiseizure activity of amiloride. In particular, posttreatment with amiloride resulted in cognitive improvement; this finding provides crucial evidence of the neuroprotective function of amiloride and of the therapeutic potential of amiloride in FS.
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Tang-Peng
authors.initials: TP
authors.lastname: Ou-Yang
authors.affiliation: Department of Neurology, Xi'an Central Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, 710032, People's Republic of China.
authors.forename: Ge-Min
authors.initials: GM
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.|Department of Human Anatomy, Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
authors.forename: Yin-Xiu
authors.initials: YX
authors.lastname: Ding
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Sun
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. jiangwen@fmmu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000584:Amiloride / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018782:Maze Learning / Q000187:drug effects; D055495:Neurogenesis; D009474:Neurons / Q000473:pathology; D017207:Rats, Sprague-Dawley; D003294:Seizures, Febrile / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
chemical_list: D027682:Cation Transport Proteins; C490997:Slc9a1 protein, mouse; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride
keywords: Amiloride; Febrile seizures; Neurogenesis; Sodium–hydrogen exchangers