title: Does angiogenesis play a role in the establishment of mesial temporal lobe epilepsy?
abstract: Mesial temporal lobe epilepsy (MTLE) is a focal epileptic disorder that is frequently associated with hippocampal sclerosis. This study investigated whether blocking angiogenesis prevents the development of seizures and hippocampal atrophy in the pilocarpine rat model of MTLE. To block angiogenesis, a subset of animals were given sunitinib orally. Continuous video recordings were performed to identify seizures. Brains were then extracted and sectioned, and hippocampal surfaces and angiogenesis were assessed. After a latent period of 6.6 ± 2.6 days, the sham-treated pilocarpine rats presented convulsive seizures, while the pilocarpine rats treated with sunitinib did not develop seizures. Sham-treated pilocarpine rats but not sunitinib-treated pilocarpine rats had significantly smaller hippocampi. Endothelial cell counts in sham-treated pilocarpine rats were significantly greater than in controls and sunitinib-treated pilocarpine rats. Blocking angiogenesis immediately following the initial insult in this animal model prevented thus angiogenesis and hippocampal atrophy and averted the development of clinical seizures.
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, Montreal Children's Hospital, Canada.
authors.forename: Ruba
authors.initials: R
authors.lastname: Benini
authors.affiliation: Division of Newborn Medicine, Department of Pediatrics, Montreal Children's Hospital, Canada.
authors.forename: Raquel
authors.initials: R
authors.lastname: Roth
authors.affiliation: Division of Newborn Medicine, Department of Pediatrics, Montreal Children's Hospital, Canada.
authors.forename: Zehra
authors.initials: Z
authors.lastname: Khoja
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
authors.forename: Massimo
authors.initials: M
authors.lastname: Avoli
authors.affiliation: Division of Newborn Medicine, Department of Pediatrics, Montreal Children's Hospital, Canada. Electronic address: pia.wintermark@bluemail.ch.
authors.forename: Pia
authors.initials: P
authors.lastname: Wintermark
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000150:complications*; D006624:Hippocampus / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D037102:Lectins / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D010862:Pilocarpine / Q000633:toxicity; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D000077210:Sunitinib; D013997:Time Factors
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D037102:Lectins; D011758:Pyrroles; D010862:Pilocarpine; D000077210:Sunitinib
keywords: Angiogenesis; Epilepsy; Hippocampus; Pilocarpine rat model