title: High-frequency stimulation of the hippocampus protects against seizure activity and hippocampal neuronal apoptosis induced by kainic acid administration in macaques.
abstract: Kainic acid (KA) administration is known to cause seizures and neuronal death in the hippocampus. High-frequency stimulation (HFS) of the hippocampus can be a promising method in the treatment of epilepsy while the mechanism of action is unknown yet. It remains unknown whether HFS is neuroprotective for hippocampal neurons following KA-induced seizures in macaques, although HFS has neuroprotective effects in animal models of Parkinson's disease. We therefore examined the effects of HFS on KA-induced seizures and neuronal survival in macaque's hippocampus. Seizure frequency following KA that led to seizures in macaques was strongly reduced by HFS of the hippocampus. In addition, administration of KA led to marked neuronal apoptosis in the hippocampus, accompanied by increased levels of Bax, activated caspase-3 and decreased levels of Bcl-2. HFS was found to attenuate changes in apoptosis-related proteins and robustly decreased neuronal loss following KA administration. These data indicate that hippocampal HFS can protect hippocampal neurons against KA neurotoxicity, and that HFS neuroprotection is likely to operate with inhibition of apoptosis.
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: N
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Neurology, The Sixth People Hospital of Jinan, Jinan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Public Health and Family Medicine, Capital Medical University, Beijing, China.
authors.forename: N
authors.initials: N
authors.lastname: Yan
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: J-G
authors.initials: JG
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
authors.forename: W-M
authors.initials: WM
authors.lastname: Xing
authors.affiliation: Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: D-M
authors.initials: DM
authors.lastname: Kong
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. Electronic address: fgmeng@ccmu.edu.cn.
authors.forename: F-G
authors.initials: FG
authors.lastname: Meng
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001703:Biophysics; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods*; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006624:Hippocampus / Q000473:pathology / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D007608:Kainic Acid / Q000633:toxicity; D008251:Macaca; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000628:therapy*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018690:Excitatory Amino Acid Agonists; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D007608:Kainic Acid
keywords: 3,3′-diaminobenzidine; DAB; DBS; EDTA; GCSs; HFS; IPG; KA; MRI; PBS; TLE; TUNEL; TdT; apoptosis; deep brain stimulation; deep brain stimulation (DBS); ethylenediaminetetraacetic acid; generalized clonic seizures; high-frequency stimulation; high-frequency stimulation (HFS); hippocampus; internal pulse generator; kainic acid; kainic acid (KA); magnetic resonance imaging; neuroprotection; phosphate-buffered saline; temporal lobe epilepsy; terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; terminal deoxynucleotidyltransferase