title: Fingolimod enhances myelin repair of hippocampus in pentylenetetrazol-induced kindling model.
abstract: Recent evidence indicates that demyelination occurs in epilepsy patients and kindling animal models. Regarding the well-known literature on anti-inflammatory and myelin protective effects of fingolimod (FTY720) in multiple sclerosis patients and animal models, we hypostatized whether FTY720 administration could exert myelin protective effects in pentylenetetrazol (PTZ)-induced kindling model. To end this, animals received 0.3 or 1mg/kg dosage of FTY720, 1h before PTZ injections. In another approach, after achieving fully kindling stage, FTY720 was administrated i.p. once daily for 7 consecutive days. Treatment with FTY720 (especially lower dose) reduced the frequency of seizures and epileptiform discharges in both approaches. We found that FTY720 administration decreases cell death and glial activation in CA1 and CA3 regions of hippocampus. Myelin protection effect was shown by increasing myelin levels. Furthermore, post-treatment of FTY720 enhanced endogenous remyelination and the number of oligodendrocyte precursor cells in fully kindled animals. Together, these results demonstrate that FTY720 behind the anti-inflammatory and neuroprotection effects has beneficial role in myelin protection and remyelination enhancement in PTZ kindling model of seizure and it may be provide a new therapeutic option for demyelination associated with epilepsy.
authors.affiliation: Student Research Committee, Faculty of Medical Sciences, Babol University of Medical Sciences, Babol, Mazandaran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Gol
authors.affiliation: Student Research Committee, Faculty of Medical Sciences, Babol University of Medical Sciences, Babol, Mazandaran, Iran.
authors.forename: Davoud
authors.initials: D
authors.lastname: Ghorbanian
authors.affiliation: Student Research Committee, Faculty of Medical Sciences, Babol University of Medical Sciences, Babol, Mazandaran, Iran.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Hassanzadeh
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Mirnajafi-Zadeh
authors.affiliation: Cellular and Molecular Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Mazandaran, Iran; Neuroscience Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Mazandaran, Iran. Electronic address: m.ghasemi@mubabol.ac.ir.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ghasemi-Kasman
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D051379:Mice; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D000068876:Fingolimod Hydrochloride; D010433:Pentylenetetrazole
keywords: Demyelination; Epilepsy; Fingolimod; Inflammation; Myelin protection; Neuroprotection