title: Radiation of the rat brain suppresses seizure-induced neurogenesis and transiently enhances excitability during kindling acquisition.
abstract: OBJECTIVE
  Adult hippocampal neurogenesis is enhanced in several models for temporal lobe epilepsy (TLE). In this study, we used low-dose whole brain radiation to suppress hippocampal neurogenesis and then studied the effect of this treatment on epileptogenesis in a kindling model for TLE.
  
  
  METHODS
  Half of the rats were exposed to a radiation dose of 8 Gy one day before the initiation of a rapid kindling protocol. Afterdischarge threshold (ADT), afterdischarge duration (ADD), clinical seizure severity, and inflammation were compared between groups. On the first and third day after radiation, rats were injected with 5'-bromo-2'-deoxyuridine (BrdU) to evaluate neurogenesis. Seven and 21 days after radiation, numbers of doublecortin (DCX) positive neuroblasts in subgranular zone and granule cell layer were compared between groups.
  
  
  RESULTS
  We showed that radiation significantly suppressed neurogenesis and neuroblast production during kindling acquisition. Radiation prevented an increase in ADT that became significantly lower in radiated rats. On the third and fourth kindling acquisition day radiated rats developed more severe seizures more rapidly, which resulted in a significantly higher mean severity score on these days. Differences in ADD could not be demonstrated.
  
  
  CONCLUSIONS
  Our results demonstrate that brain radiation with a relatively low dose effectively suppressed the generation of new granule cells and transiently enhanced excitability during kindling acquisition. Although seizure-induced neurogenesis was lower in the radiated rats we could not detect a strong effect on the final establishment of the permanent fully kindled state, which argues against a prominent role of seizure-induced neurogenesis in epileptogenesis.
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Department of Neurology, Ghent University Hospital, Ghent, Belgium. Robrecht.Raedt@UGent.be
authors.forename: Robrecht
authors.initials: R
authors.lastname: Raedt
authors.forename: Paul
authors.initials: P
authors.lastname: Boon
authors.forename: Asa
authors.initials: A
authors.lastname: Persson
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Alborn
authors.forename: Tom
authors.initials: T
authors.lastname: Boterberg
authors.forename: Annelies
authors.initials: A
authors.lastname: Van Dycke
authors.forename: Birgit
authors.initials: B
authors.lastname: Linder
authors.forename: Tim
authors.initials: T
authors.lastname: De Smedt
authors.forename: Wytse J
authors.initials: WJ
authors.lastname: Wadman
authors.forename: Elinor
authors.initials: E
authors.lastname: Ben-Menachem
authors.forename: Peter S
authors.initials: PS
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology / Q000528:radiation effects; D001921:Brain / Q000503:physiopathology / Q000528:radiation effects*; D001973:Bromodeoxyuridine / Q000378:metabolism; D004396:Coloring Agents / Q000378:metabolism; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000706:statistics & numerical data; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology / Q000528:radiation effects; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000502:physiology* / Q000528:radiation effects*; D009474:Neurons / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects*; D011829:Radiation Dosage; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology*; D013234:Stem Cells / Q000502:physiology / Q000528:radiation effects*; D013238:Stereotaxic Techniques
chemical_list: D004396:Coloring Agents; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D001973:Bromodeoxyuridine