title: Long-Term Treatment with Losartan Attenuates Seizure Activity and Neuronal Damage Without Affecting Behavioral Changes in a Model of Co-morbid Hypertension and Epilepsy.
abstract: Over the last 10 years, accumulated experimental and clinical evidence has supported the idea that AT1 receptor subtype is involved in epilepsy. Recently, we have shown that the selective AT1 receptor antagonist losartan attenuates epileptogenesis and exerts neuroprotection in the CA1 area of the hippocampus in epileptic Wistar rats. This study aimed to verify the efficacy of long-term treatment with losartan (10 mg/kg) after kainate-induced status epilepticus (SE) on seizure activity, behavioral and biochemical changes, and neuronal damage in a model of co-morbid hypertension and epilepsy. Spontaneous seizures were video- and EEG-monitored in spontaneously hypertensive rats (SHRs) for a 16-week period after SE. The behavior was analyzed by open field, elevated plus maze, sugar preference test, and forced swim test. The levels of serotonin in the hippocampus and neuronal loss were estimated by HPLC and hematoxylin and eosin staining, respectively. The AT1 receptor antagonism delayed the onset of seizures and alleviated their frequency and duration during and after discontinuation of treatment. Losartan showed neuroprotection mostly in the CA3 area of the hippocampus and the septo-temporal hilus of the dentate gyrus in SHRs. However, the AT1 receptor antagonist did not exert a substantial influence on concomitant with epilepsy behavioral changes and decreased 5-HT levels in the hippocampus. Our results suggest that the antihypertensive therapy with an AT1 receptor blocker might be effective against seizure activity and neuronal damage in a co-morbid hypertension and epilepsy.
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 23, 1113, Sofia, Bulgaria. janetchekalarova@gmail.com.
authors.forename: Jana D
authors.initials: JD
authors.lastname: Tchekalarova
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 23, 1113, Sofia, Bulgaria.
authors.forename: Natasha
authors.initials: N
authors.lastname: Ivanova
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 23, 1113, Sofia, Bulgaria.
authors.forename: Dimitrina
authors.initials: D
authors.lastname: Atanasova
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 23, 1113, Sofia, Bulgaria.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Pechlivanova
authors.affiliation: Department of Anatomy, Medical Faculty, MU-Sofia, Sofia, Bulgaria.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Lazarov
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 23, 1113, Sofia, Bulgaria.
authors.forename: Lidia
authors.initials: L
authors.lastname: Kortenska
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 23, 1113, Sofia, Bulgaria.
authors.forename: Rumiana
authors.initials: R
authors.lastname: Mitreva
authors.affiliation: Department of Medical Chemistry and Biochemistry, Sofia, Bulgaria.
authors.forename: Valentin
authors.initials: V
authors.lastname: Lozanov
authors.affiliation: Department of Pathophysiology, Medical Faculty, MU-Sofia, Sofia, Bulgaria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stoynev
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects*; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D012640:Seizures / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013226:Status Epilepticus / Q000139:chemically induced
chemical_list: D019808:Losartan
keywords: AT1 receptor antagonism; Behavior; Hippocampus; Kainate; Serotonin; Spontaneous recurrent seizures