title: Long-term intracerebroventricular infusion of angiotensin II after kainate-induced status epilepticus: Effects on epileptogenesis, brain damage, and diurnal behavioral changes.
abstract: Our previous studies revealed that Angiotensin (Ang) II has anticonvulsant effects in acute seizure models. However, data on its role in experimental models of epilepsy are missing. In the present study, we tested whether posttreatment with Ang II after kainate (KA)-induced status epilepticus (SE) can affect epileptogenesis, concomitant behavioral changes, and brain damage. The Wistar rats were intracerebroventricularly infused via osmotic mini-pumps with Ang II (1.52μg/μl/day for 28days) after SE. Spontaneous motor seizures (SMS) were video-recorded for up to three months. Locomotor activity, anxiety, and depression-like behavior were evaluated during the last week of drug infusion, while spatial memory was assessed during the 3rd month after SE. Angiotensin II decreased the latency for onset of the first SMS and increased the frequency of SMS two months after SE. The continuous peptide infusion exacerbated the KA-induced hyperactivity and caused depression-like behavior. The reduced anxiety of KA-treated rats was alleviated by Ang II exposure. The KA-induced deficit in the hippocampal-dependent spatial memory was not influenced by Ang II. However, Ang II partially prevented the neuronal damage in the hippocampus, specifically in the CA1 area. The role of AT1 and AT2 receptor activation in the effects of the octapeptide is discussed.
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Natasha M
authors.initials: NM
authors.lastname: Ivanova
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Dimitrina
authors.initials: D
authors.lastname: Atanasova
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Pechlivanova
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Rumyana
authors.initials: R
authors.lastname: Mitreva
authors.affiliation: Department of Anatomy, Medical Faculty, MU-Sofia, Bulgaria.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Lazarov
authors.affiliation: Department of Pathophysiology, Medical Faculty, MU-Sofia, Bulgaria.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Stoynev
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria. Electronic address: janetchekalarova@gmail.com.
authors.forename: Jana D
authors.initials: JD
authors.lastname: Tchekalarova
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000473:pathology; D002940:Circadian Rhythm / Q000187:drug effects*; D004195:Disease Models, Animal; D057967:Infusions, Intraventricular; D007608:Kainic Acid / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects*; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D018696:Neuroprotective Agents; D000804:Angiotensin II; D007608:Kainic Acid
keywords: Angiotensin II; Behavior; Brain damage; Diurnal rhythms; Kainate