title: Hyperthermia aggravates status epilepticus-induced epileptogenesis and neuronal loss in immature rats.
abstract: This study tightly controlled seizure duration and severity during status epilepticus (SE) in postnatal day 10 (P10) rats, in order to isolate hyperthermia as the main variable and to study its consequences. Body temperature was maintained at 39 ± 1 °C in hyperthermic SE rats (HT+SE) or at 35 ± 1 °C in normothermic SE animals (NT+SE) during 30 min of SE, which was induced by lithium-pilocarpine (3 mEq/kg, 60 mg/kg) and terminated by diazepam and cooling to NT. All video/EEG measures of SE severity were similar between HT+SE and NT+SE pups. At 24h, neuronal injury was present in the amygdala in the HT+SE group only, and was far more severe in the hippocampus in HT+SE than NT+SE pups. Separate groups of animals were monitored four months later for spontaneous recurrent seizures (SRS). Only HT+SE animals developed convulsive SRS. Both HT+SE and NT+SE animals developed electrographic SRS (83% vs. 55%), but SRS frequency and severity were higher in hyperthermic animals (12.5 ± 3.5 vs. 4.2 ± 2.0 SRS/day). The density of hilar neurons was lower, thickness of the amygdala and perirhinal cortex was reduced, and lateral ventricles were enlarged in HT+SE over NT+SE littermates and HT/NT controls. In this model, hyperthermia greatly increased the epileptogenicity of SE and its neuropathological sequelae.
authors.affiliation: Veterans Administration Greater Los Angeles Healthcare System, Epilepsy Research (151), 11 301 Wilshire Boulevard, Building 114, Room 139, Los Angeles, CA 90073, USA. Electronic address: lsuchomelova@yahoo.com.
authors.forename: L
authors.initials: L
authors.lastname: Suchomelova
authors.affiliation: Centro de Investigaciones Cerebrales, Universidad Veracruzana, Veracruz 91190, Mexico.
authors.forename: M L
authors.initials: ML
authors.lastname: Lopez-Meraz
authors.affiliation: Veterans Administration Greater Los Angeles Healthcare System, Epilepsy Research (151), 11 301 Wilshire Boulevard, Building 114, Room 139, Los Angeles, CA 90073, USA.
authors.forename: J
authors.initials: J
authors.lastname: Niquet
authors.affiliation: Department of Developmental Epileptology, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, Prague 14220, Czech Republic.
authors.forename: H
authors.initials: H
authors.lastname: Kubova
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, VA Medical Center (127), 11 301 Wilshire Boulevard, Los Angeles, CA 90073, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Wasterlain
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D016923:Cell Death / Q000187:drug effects; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D006979:Hyperthermia, Induced / Q000009:adverse effects*; D018021:Lithium Chloride / Q000633:toxicity; D008297:Male; D018721:Muscarinic Agonists / Q000633:toxicity; D009410:Nerve Degeneration / Q000209:etiology*; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D019581:Neuropil / Q000473:pathology / Q000648:ultrastructure; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000209:etiology*; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D000927:Anticonvulsants; D018721:Muscarinic Agonists; D010862:Pilocarpine; D018021:Lithium Chloride; D003975:Diazepam
keywords: EEG monitoring; immature brain; lithium/pilocarpine model; neuronal injury; temperature